Thesis - The development of the blood supply to the human embryo basal ganglia
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Stewart GG. The development of the blood supply to the human embryo basal ganglia. (1955) University of Alberta, Canada.
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- 1 The Development of the Blood Supply to the Human Embryo Basal Ganglia
- 1.1 Abstract
- 1.2 Introduction
- 1.3 Comparative Anatomy of the Forebrain Blood Supply
- 1.4 Methods and Materials
- 1.5 Embryo A
- 1.6 EMBRYO B
- 1.7 EMBRYO C
- 1.8 EMBRYO D
- 1.9 Embryo E
- 1.10 Bibliography
The Development of the Blood Supply to the Human Embryo Basal Ganglia
The adult basal ganglia have originated in three different projections and their arterial supply develops from three independent systems of arteries which appear in definitive form at various stages in the embryo's growth. The three systems of arteries are the striate arteries, the olfactory arteries and the choroidal arteries (optic system).
The striate arteries and veins are in their definitive form at the 12.5 mm. stage. The palaeo-striatal region is well established (medial hillock) and gains its blood supply from the striate branches of the anterior cerebral artery. The neo-striatum forms the more slowly developing lateral hillock and is gaining its blood supply from the striate branches of the middle cerebral artery. Between the middle and anterior cerebral arteries is a series of anastomoses forming the primitive olfactory system, no specific vessel of which is well defined. The choroidal branches form a primitive junction over the lateral geniculate body, all their blood being directed to that body.
By the 15.0 mm stage the anterior set of vessels in the olfactory anastomosing series, in response to the anterior growth of the head of the caudate nucleus, has formed the recurrent artery of Heubner with its definitive morphology and area of supply. It is this series of anastomoses which accounts for mary of the possible abnormalities assumed by Heubner’s artery.
At the 20 mm stage the internal capsule appears in the hemispheric stalk, imperfectly dividing the corpus striatum. The anterior choroidal artery ascends along the optic tract posterior to this stalk to its distribution in the choroid plexus and lateral geniculate body. In so doing it provides branches to the posterior extension of the basal ganglia.
By the 25 mm stage this supply from the anterior choroidal artery extends as definitive branches to all aspects of this posterior extension. The anterior communicating artery is established as a definitive branch, at this stage, but abnormalities involving the recurrent artery are usually accompanied by retention of some aspect of a primitive plexus across this communication. The morphology of the circle of Willis is little changed by the 33 mm. stage.
The striate veins achieve their definitive morphology along with the striate arteries, but at the 12.5 mm. stage the superior drainage system is represented by a simple plexus, the primordium of the superior sagittal plexus, by the 15 mm. stage the velum has differentiated the straight sinus, forming in the roof of the diencephalon and the anterior branches of which drain both the primitive choroid plexus and the superior aspect of the caudate nucleus. By 20 mm. this anterior drainage has elaborated the internal cerebral veins which drain each hemisphere separately. At the 25 mm. stage the venous drainage extends to the regions supplied by choroidal and striate arteries. The posterior terminal vein lies in the terminal sulcus but the future anastomosis of this vessel with the cerebral vessels is not yet in evidence.
The author wishes to express his appreciation for the kind help and direction of Dr, R. F. Shaner under whose direction this work was undertaken. Professor W. R. Salt freely offered a great deal of assistance when difficulties presented themselves and Dr. J. S. Thompson offered helpful suggestions in matters of technique, all of which were most appreciated.
The author would like to express appreciation to Mr. R. Adair for his advice concerning the various histological techniques employed and to Mr. R. Seward for his co-operation in numerous ways.
The author would like to thank the National Research Council for the grant which helped considerably this undertaking.
The co-operation of the medical staffs of the Royal Alexandra, University, Misericord!a and General hospitals made possible the procuring ox the embryos used in this study.
|A.C.A. anterior cerebral artery
A.CH.A. anterior choroidal artery
A.CO.A. anterior communicating artery
A. COM. anterior commissure
A.P. anterior plexus
B.A. basilar artery
CER.E. cerebral hemisphere
C.N. corpus striatum (caudate nucleus)
CO.P. collicular plate
C.P. cerebellar plate
D.A. diencephalic artery
D.C.A. diencephalic artery
D.TH. dorsal thalamus
F. of M. foramen of Monro
H.N. habenular nucleus
HYP.A.L. hypophysis anterior lobe
I.G. internal capsule
I.C.A. Internal carotid artery
I.C.V. internal cerebral vein.
IT.S. intrathalamic sulcus
L.G.B. lateral geniculate boc^r
L.S.A. lateral striate arteries
M.A. mesencephalic artery
M.A.C.C. medial artery of the corpus sallosum
M.C.A. middle cerebral artery
M.R. mammalary recess
M.S.A. medial striate artery (Heubner's recurrent)
|O.A. ophthalmic artery
O.G. optic groove
OLF.N. olfactory nerve
OLF.TUB. olfactory tubercle
Q.N. optic nerve
O.R. optic recess
O x putamen
P.C. posterior commissure
PC. A. posterior communicating artery
P.CO.A. posterior communicating artery
P.CH.A. posterior choroidal artery
P.I.C.A. posterior inferior cerebellar artery
PIT. pituitary gland primordium
P.O.A. primitive olfactory artery
PO.R. pre-optic recess
5.C.A. superior cerebellar artery
S.D.TH. dorsal thalamic sulcus
S.M.TH. medial thalamic sulcus
S.O.N. supra-optic nucleus
S.P.C.A. superior portion of the posterior cerebral artery
s.s. straight sinus
S.S.P. superior sagittal sinus
STAPES.A. stapedial artery
S.V.TH. ventral thalamic sulcus
V.A. vertebral artery
VEL. INTER. velum interpositum
V.S. ventricular sulcus
V.TH. ventral thalamus
Z.IT. zona intrathamica
THE BLOOD SUPPLY TO THE ADULT HUMAN FOREBRAIN WITH SPECIAL REFERENCE TO THE CORPUS STRIATUM NUCLEI:
The basal nuclei are:
- the caudate and lentiform nuclei, which together form the corpus striatum,
- the claustrum.
- the auygdaloid nucleus.
The corpus striatum, with the included internal capsule, is the special focus of our attention. The following review of adult morphology was taken from various texts on neuroanatony including Strong and Eliyn's "Human Neuroanatomy", Cunningham's Manual and others and has been included only in bare outline as finer details may be sought out in these texts.
The corpus striatum arises in the embjyo as a single gray mass and becomes secondarily divided by the fibers of the internal capsule into two cellular masses, the caudate nucleus and the lenticular nucleus. This separation is not complete. In its most rostral portion, the head of the caudate is ventrally continuous with the lenticular nucleus, and more dors ally the two nuclei are connected ty a number of slender gray bridges extending across the internal capsule* These bridges give the striped appearance which has led to the designation of corpus striatum.
The caudate nucleus is an elongate arched gray mass related throughout its extent to the ventricular surface of the lateral ventricle. Its enlarged anterior portion, or head, lies rostral to the thalamus and bulges into the anterior horn. Its long attenuated caudal portion, or tail, extends along the dorsolateral border of the thalamus, separated from the latter ty the terminal sulcus. This longitudinal groove marks the zone of junction between the corpus striatum and the thalamus and contains the stria terminalis, an olfactoiy tract, and the terminal vein. On reaching the caudal limit of the thalamus, the tail arches vent rally and runs forward in the roof of the inferior horn to reach the auygdaloid nucleus.
The lenticular nucleus has the form of a wedge whose broad convex base is directed laterally. It has no ventricular surface but lies deeply buried in the white matter of the hemisphere closely applied to the lateral surface of the internal capsule which separates it from the caudate nucleus and the thalamus. A vertical plate of white matter divides the nucleus into an outer larger portion, the putamen, and an inner portion known as the globus pallidus. It receives its name from the pale appearance it has on section due to the large number of nyelinated fibers it contains.
The putamen and caudate nuclei constitute the phylogenetically newer part of the striate complex (neostriatum) while the phylogenetically older globus pallidus belongs to the paleo-striatum. These structures are $meTmally linked together so constituting an older or extrapyramidal motor system, in existence long before the advent of the motor cortex and pyramidal tract, but which is now under the dominance of the cerebral cortex. In animals without a cortex or with a poorly developed one, the corpus striatum is the most important center on whose integrity depend the largely instinctive activities of these forms, such as locomotion, defense, feeding, courtship, etc. Thus in submammalian forms the diencephalon and corpus striatum together constitute the highest sensoiy-motor integrating mechanism of the forebrain, the thalamus representing the receptive center, the corpus striatum and hypothalamus related to motor control. With the evolution of the neopallium to the human level, the basal ganglia have possibly a different significance, playing a role in maintenance of muscle tone, gross synergic movements of locomotion, expression and postural adjustment, and those semi-automatic movements which are normally associated with voluntary activities, such as swinging the arms in walking.
Some believe the corpus striatum is capable of initiating such movements in the human, others relegating it to a purely regulatory function.
The fibers which connect the thalamus and cortex in both directions constitute the thalamic radiations which are the major portion of the internal capsule. These thalamocortical and corticothalamic fibers form a continuous fan emerging along the whole lateral extent of the caudate nucleus and whose radiations connect with practically all parts of t3ie cortex. As well, the cerebral hemisphere is connected with the brain stem and spinal cord by an extensive system of projection fibers, some afferent, others efferent. These fibers, mixed with the thalamic radiations form the broad compact fiber band, the internal capsule, flanked medially by the thalamus and caudate nucleus, laterally by the lenticular nucleus.
The internal capsule is thus composed of all fibers, afferent and efferent, which go to or come from the cerebral cortex. On horizontal section, the internal capsule is composed of a shorter anterior and a longer posterior limb which meet at an obtuse angle, the genu portion of the internal capsule. The anterior limb lies between the lenticular and caudate nuclei, while the posterior limb lies between the lenticular nucleus and the thalamus.
Another nuclear mass of importance in the present study is the lateral geniculate body and its optic tract connections, all of which lie in the diencephalon. From the optic chiasma, each optic tract sweeps outward and backward encircling the hypothalamus to terminate in the lateral geniculate body, as well as in the superior calliculi and other diencephalic centers. This bocfy, along with the pulvinar, is a large nuclear mass forming the posterior position of the thalamus. In most mammals the lateral geniculate booty consists of a dorsal and a ventral nucleus, the former connected with the ventral thalamus and pulvinar, the latter apparently representing a subthalamic structure. In man the ventral nucleus is practically indistinguishable,
The whole brain is supplied ty two pair of arterial trunks, the two carotid arteries supplying the rostral half of the brain, and the two vertebrals supplying the caudal half of the brain. It is the former with which we are primarily interested, the branches of the internal carotids supxolying, along with anterior sections of the hemispheres, the thalamus, the corpus striatum, and practically all of the internal capsule.
On the basal surface of the brain the four main arterial trunks form an anastomosing system known as the circle of Willis, The two vertebral arteries entering the foramen magnum run forward on the ventral surface of the medulla to fuse and form the unpaired basilar artery • At the rostral border of the pons, this artery bifurcates into the two posterior cerebral arteries. The internal carotid artery enters the cranial posterior through the carotid foramen and reaches the base of the brain just lateral to the optic chiasma, Here it divides into its two terminal branches:
(1) the smaller anterior cerebral artery and (2) the larger middle cerebral artery which may, in man, be regarded as the direct continuation of the carotid artery• At, or immediately before its division, the carotid gives off the posterior communicating artery which runs backward and anastomoses with the proximal portion of the posterior cerebral artery. The anterior cerebral artery runs medially and rostrally towards the interhemispheric fissure and in front of the optic chiasma is joined to its mate by a short connecting channel, the anterior communieating artery. This completes the arterial circle of Willis.
From the circle of Willis and the three main cerebral arteries arise two main types of branches, the cortical with which we are not concerned, and the central. The latter vessels arise from the circle of Willis and the proximal portions of the three cerebral arteries, dip perpendicularly into the brain substance and irrigate the diencephalon, the corpus striatum and internal capsule. For the sake of clarity, these central branches are arranged into three subgroups: (l) The medial striate artery or the recurrent artery of Heubner which arises near the level of the anterior communicating artery, runs posteriorly and laterally, dips into the anterior perforated space and supplies the antero- ventral portion of the head of the caudate-putamen nuclei and adjacent internal capsule. (2) The lateral striate vessels of which there are four main groups: a) anterior striate vessels arising from the anterior cerebral and anterior communicating arteries, dip into the medial portion of the anterior perforated space to be distributed to the anterior hypothalamus. b) and c) th o se■div 4s4on€-are posterior striate vessels arising from the posterior cerebral and posterior communicating arteries supplying the hypothalamus and the anterior and medial portions of the thalamus, the more posterior vessels supplying the posterior portion of the thalamus and geniculate bodies, d) anterolateral striate vessels arise from the basal portion of the middle cerebral artery, pierce the perforated space to supply the anteroventral head of the caudate-putamen nuclei and adjacent internal capsule, as well as most of the body of the putamen, caudate nucleus, dorsal portions of both limbs of the internal capsule, and lateral part of the globus pallidus. (3) The choroidal vessels, anterior and posterior, which may be regarded as specialized branches of the striate vessels.
The anterior choroidal artery arises either from the middle cerebral artery or the internal carotid artery, close to the origin of the posterior communicating artery. It passes backward along the optic tract, some of its branches perforating the latter, and enters the choroidal fissure in the lower part of the inferior horn. This artery supplies the choroid plexus of the lateral ventricle, the hippocampus, the medial and intermediate portions of the globus pallidus and the larger ventral part of the posterior limb of the internal capsule, including the entire retrolenticular portion of the capsule. It also sends branches to the amygdaloid nucleus, the recurving ventral portion of the caudate tail and posterior tip of the putamen, the pulvinar and lateral geniculate body.
The posterior choroidal arteries, of which there are usually two, are branches of the posterior cerebral artery. They encircle the cerebral peduncles and after giving off branches to the midbrain roof, are distributed to the choroid plexus of the third ventricle and to the superomedial surface of the thalamus.
In summary — the striatum is supplied by three sets of arteries:
- The anteroventral portion of the head of the caudate- putamen nuclei is supplied by the medial striate artery.
- The main bodies of the caudate and putamen nuclei are supplied by the lateral striate vessels arising mainly from the middle cerebral arteries and to a lesser extent from the anterior cerebral arteries.
- The recurving portion of the tail of the caudate, the posterior tip of the putamen and the anygdaloid nucleus receive their blood supply from the anterior choroidal artery.
The medial and intermediate segments of the pallidus are fed ly the anterior choroid artery, while the lateral segment has a variable supply between this vessel and striate vessels.
The internal capsule receives its blood supply from various sources. The dorsal portions of both the anterior and posterior limbs receive their blood supply from the lateral striate branches. The ventral portions of the anterior limb is fed by the medial striate artery. The ventral portion of the posterior limb, as well as the entire retrolenticu- lar portion of the capsule, are fed ty the anterior choroidal artery. The genu as a rule, receives one or two direct twigs from the internal carotid or posterior communicating arteries.
The superior sagittal sinus extends from the foramen cecum to the internal occipital protuberance, lying along the attached border of the falx cerebi. The inferior sagittal sinus extends caudally along the free border of the falx to the anterior border of the tentorium 'where it is joined ly the great cerebral vein of Galen, which drains the deep structures of the brain. The two are continued as the straight sinus which runs backwards and downwards along the line of attachment of falx and tentorium and joins the superior sagittal sinus near the internal occipital protuberance.
The cerebral veins, like the arteries, are divided into cortical branches, with which we are not here concerned, and central branches. The veins, as a rule, run separately from the arteries however. The central veins drain the choroid plexuses of the forebrain, the basal ganglia and dorsal portions of the diencephalon. These veins are collected into the great vein of Galen. The central and cortical veins are not distinct and are widely interconnected by anastomotic channels, both intracerebral and extracerebral.
The central group of veins is composed of the two internal cerebral veins which in turn drain into the vein of Galen. Each internal vein drains a separate hemisphere.
At or near the bifurcation, each internal cerebral vein gives off the lateral ventricular vein which runs laterally on the superior surface of the thalamus and tail of the caudate nucleus. The two internal cerebral veins then pass anteriorly in the velum interposituin (roof of the third ventricle), and in the region of the foramen of Monro each vein breaks up into its terminal tributaries. The small choroidal vein runs along the lateral border of the choroid plexus into the inferior horn. It drains the plexus and adjacent hippocampal regions. Additional drainage of the plexus is through the choroid branch of the basal vein, and to a smaller extent, the small branch of the lateral ventricular vein.
The posterior terminal vein runs posteriorly, opposite to its parent internal cerebral vein, in the terminal sulcus between the thalamus and caudate nucleus. The anterior terminal vein runs forward and branches in the head of the caudate nucleus. Both vessels receive tributaries, the transverse caudate veins, which cross the caudate nucleus, reach the lateral angle of the ventricle and enter the adjacent white substance of the brain. Here they change their direction abruptly to form the longitudinal caudate veins. From here anastomotic channels fan superiorly into the superior sagittal plexus, medially into the superficial middle vein, and inferiorly into the deep middle vein.
The above description of the blood supply to the fore brain is a highly controversial one and this description was used as a basis to which problems could be related, Vaiying views of different investigators will be outlined below. Part of the controvert arises as a result of using different methods and materials in stuping the arterial systems, and partly as a result of confusion in nomenclature.
The purpose of this stuc^r is to present an account of the embryology of fore brain blood supply in the human, with particular reference to the caudate nucleus in the basal ganglia. Previous investigations of this nature have usually been of two distinct types depending on the nature of the material and methods:
1. Those primarily concerned with exact limits of supply of individual vessels to particular regions and structures in the brain.
This has usually been carried out fcy gross dissection of injected adult human brains. The prime intention has been to determine clinical significance due to the field limits of blood supply within the adult brain, the relative anatony of these fields and the amount of variation present. One area of controversy concerned with this type of investigation is whether central arteries are end arteries or whether there is anastomosis between the vessels. Do the fields of supply of the various groups of central arteries overlap?
2. Those interested in the morphology of the vessel systems without particular regard to the exact area of supply of the vessels. This has usually been carried out ty gross dissection of injected adult vertebrate brains or from an embiy ©logical point of view. This approach is concerned with the evolution of cerebral vessels, that these changes may explain the variety of pattern of the major vessels and the difference in distribution in different animals. A notable contribution to this field of investigation in the human Embryo was made ty Dorcas Hager Paget in 1943 in ”Contributions to Embryology", No. 525.
This second general approach was used as a broad basis for the present investigation, with the following modifications. Shellshear (1920) developed the concept of vessel-organ unity that is constant in ontogeny and phylogeny and based this concept upon two basic principles:
1. Vessels are laid down with a definite relationship to function.
2. Distribution of vessels obeys some definite ontogenic and phylogenetic law.
A. A. Abbie (1933-1934) developed these concepts in a comparative study of adult vertebrates of the relationship of blood supply to the developing centers of the brain. The present investigation was done in the light of the latter concepts with particular regard to the basal ganglia and its blood supply as an organ-unit in the human Embryo. The essential problems were outlined by the following studies:
1. Gross dissection of adult human brains in order to gain a picture of the relationship of arteries and veins to the basal ganglia. This was carried out on material provided by the Anatony Department of the University of Alberta.
2. An examination of the literature to gain an understanding of the development of the basal ganglia in vertebrates and the consequent development of its blood supply. The controversial elements regarding this blood supply were investigated.
3. Original research on human Embryos to obtain a picture of the growth of the basal ganglia and its blood supply in the human and to explain such abnormalities as vestigial vessels and abnormal morphology of the circle of Willis and its branches. This aspect of the investigation is discussed in relation to the plates and figures.
A survey of the literature revealed that most investigators interested in forebrain blood supply were interested in some specific aspect of the problem; many were concerned with establishing exactly the adult human blood supply, others in the embiy ©logical development of such vessels, some were concerned with the embryological development of nuclei in the forebrain while still others concerned themselves with the comparative anatony of this region.
Mary differences of opinion arise among the investigators who have attempted to establish the adult human forebrain blood supply. Alexander (1942) established a clear cut circulatory cleavage between the striatum (caudate nucleus and putamen) and the globus pallidus. He insisted that adjacent districts of arterial supply do not overlap in the human brain. The method he used was dissection of human adult brains either with or without injection. Alexander stated that the strio- pallidum receives its blood supply from two groups of vessels:
I. Striate arterioles from -
a. mostly the middle cerebral artery.
b. fewer, the anterior cerebral artery, (1/3 from a. only).
II. Anterior choroidal artery.
The striate arterioles, from (a) the middle cerebral artery, leave the main branch of the middle cerebral artery at right angles, traverse the subarachnoid space parallel to each other and enter the canalicular openings in the anterior perforated space. There are from two to nine such arterioles branching from the middle cerebral artery on each side. Occasionally 1 one bifurcates or divides into more than two channels.
Therefore, three to eleven separate branches may enter the perforated space. On an average, five branches leave the artery and enter the brain on each side.
The striate arterioles from (b), the anterior cerebral artery are less numerous and have a vaiying constancy. ¥ith bifurcation, one to four branches enter the medial part of the perforated space on each side.
The anterior choroidal artery arises as a direct branch from the carotid artery, runs posteriorly over a considerable stretch of the basal surface of the brain along the optic tract. Close to the posterior end of the optic tract the pallial branches come off, cross the optic tract, enter the brain substance to recurve anteriorly within the brain into the globus pallidus. The free intracranial course of the anterior choroidal artery through the arachnoid space is three times that of most striate arterioles.
Injections through the striate branches of the middle cerebral artery fill the c&pillaiy bed of the major part of the striatum except for the posterior ventral recurved part of the tail of the caudate nucleus and adjoining posteroventral crest of the putamen, which are supplied by the anterior choroidal artery. In two-thirds of the cases, the anterior tips of the head of the caudate nucleus and of the putamen are supplied by the striate branches of the anterior cerebral artery. It is in relation to this particular problem of the variable blood supply to the head of the caudate and putamen nuclei that the present investigation of Heubner 1 s artery was undertaken.
Alexander further indicates that the striate arterioles of the middle cerebral artery supply the internal capsule adjacent to the striatum supplied by these branches; i.e., in one-third of the cases all of tne anterior limb of the internal capsule, the dorsolateral part adjacent to the knee, and the dorsal part of the posterior limb. The capillary bed of the medial and intermediate segments of the globus pallidus are filled •when the anterior choroidal artery was vestigial.
The lateral segment of the globus pallidus, with the exception of its anteroventral tip, is supplied from the striate branches of the middle cerebral artery entirely in one-quarter of cases, the anteroventral tip of the lateral segment of the globus pallidus supplied from the striate branches of the middle cerebral artery in about that third of cases in which the anteroventral tip of the caudate nucleus and ventromedial part of the anterior limb of the internal capsule are likewise supplied.
Rubenstein (1944) paid particular attention to the "recurrent artery of the anterior cerebral artery." It arises from the anterior cerebral artery at the level of the anterior communicating artery, passes laterally and divides into several twigs, one to the external capsule, another to the anterolateral aspect of the lentiform nucleus and continues medially into the head of the caudate nucleus and the anterior limb of the internal capsule. In all, Rubenstein traced several small twigs from this artery into the anterior limb of the internal capsule. He also noted the presence of accessory recurrent arteries. When one of these vessels is present it may be given off from the lateral aspect of the anterior cerebral artery approximately midway between its origin and its anterior communicating branch. When present, the accessory recurrent artery sends branches which may parallel in distribution the branches of the recurrent artery. Both accessory and recurrent arteries may be absent bilaterally or present on one side and absent on the other. Twigs from the middle cerebral artery then supply the area previously described as being supplied iy the recurrent arteries. Rubenstein further noted centrally directed branches of the middle cerebral artery supplying the lateral hypothalamus as well as marked branches to the anterior limb, genu and anterior two-thirds of the posterior limb of the internal capsule. For this reason, Rubenstein maintains that all parts of the internal capsule have a multiple blood supply. His observations are at variance -with those of Alexander, especially regarding the specificity of blood supply. To the anterior limb and the dorsal part of the posterior limb of the internal capsule, Alexander ascribes the striate arterioles, to the genu the ventral part of the posterior limb and the retrolenticular component, the anterior choroidal artery. Therefore, Rubenstein agrees with him on the anterior limb since Alexander derives the striate arterioles from both the anterior and middle cerebral arteries. The greatest difference relates to the genu to which area Rubenstein has traced branches of the anterior cerebral artery, the middle cerebral artery, the posterior communicating artery (when present) and the anterior choroidal artery.
Fae Tichy (1949) studied the adult human forebrain blood supply ty means of injections and dissections. She followed three or four basal branches of the anterior cerebral artery which pierces the anterior perforated substance to supply the head of the caudate nucleus. She includes as one of these, the recurrent artery of Heubner which supplies the following structures:
- Olfactory peduncle.
- Anterior part of the caudate nucleus.
- Anterior third of the putamen.
- Tip of the outer segment of the globus pallidus.
- Anterior limb of the internal capsule.
Rubenstein includes the external capsule and the genu of the internal capsule in the distribution of the recurrent artery.
The basal branches of the middle cerebral artery supply:
- Superior half of the anterior and posterior divisions of the internal capsule.
- Superior half of the head of the caudate nucleus and the horizontal part of the caudate.
- The external and middle segments of the lentiform nucleus.
- The lateral parts of the anterior commissure.
Tichy also stressed the distribution of the anterior choroidal artery and the posterior communicating artery„ The anterior choroidal artery arises from the internal carotid artery between the origins of the posterior communicating and middle cerebral arteries. It crosses the optic tract and runs posteriorly along the medial border of the tract against the cerebral peduncle. At the lateral geniculate body it divides into many branches, most of which recross the optic tract to enter the inferior horn of the lateral ventricle and reach the choroid plexus. The two terminal branches run posteriorly over the lateral geniculate boc^r to join the posterior cerebral and posterior choroidal arteries. Its field of distribution!
- The optic tract.
- The posterior two-thirds of the inferior half of the posterior limb of the internal capsule.
- The optic radiation.
- The pes pedunculi.
- The tail of the caudate nucleus.
- The inner segment of the lenticular nucleus.
- The choroid plexus in the descending and posterior cornua.
- The amygdaloid nucleus.
- The outer part of the anterior commissure.
- The uncinate gyrus.
Abbie also included the substantia nigra, the red nucleus, the subthalamic body, the ventral lateral nucleus of the thalamus, the lateral and anterior parts of the lateral geniculate bocftr, the stria terminalis and most of the globus pallidus.
The posterior communicating artery arises from the internal carotid artery just before it divides into the anterior and middle cerebral artery and passes posteriorly to join the posterior cerebral artery. Its branches go:
- The optic chiasma.
- The subthalamic region.
- Anterior pes pedunculi.
- The anterior third of the posterior division of the internal capsule.
- The external and internal nuclei of the thalamus.
The posterior cerebral artery arises from the bifurcation of the basilar artery, runs outwards and posteriorly around the cerebral pedunucli, receives the posterior communieating artery and passes onto the inferior surface of the occipital lobe. Its basal branches supply:
- Mammilary bodies.
- Posterior pes pedunculi.
- Red nucleus.
- The thalamus.
- The choroid plexus of the lateral ventricles.
- The medial geniculate bodies and the medial and posterior aspects of the lateral geniculate body.
- The bodies and posterior parts of the fornices. Others have included the posterior limb of the internal capsule in the field of supply of the posterior cerebral artery.
Beevor (1909) outlined an overlap in the vascular supply to the internal capsule from four vessels as follows:
The inferior half of its anterior limb is supplied ty the anterior cerebral artery, the superior half ty the middle cerebral artery. The anterior part of the genu is supplied by the anterior cerebral artery, the posterior half by the posterior communicating artery. The superior half of the posterior limb is supplied by the middle cerebral artery, the inferior half is supplied ty the posterior communicating artery (in the anterior one-'third) and the anterior choroidal artery (in the posterior two-thirds).
Ayer and Aiken (1907) emphasized the course of the branches of the anterior cerebral arteries* particularly the recurrent branch. Sections of the brain for these vessels should be in sagittal section instead of cross section, for the arteries of the corpus striatum enter the anterior perforated space in order at about right angle to the longitudinal fissure. Predominating ones at once bend outward toward the exterior wall of the lentiform nucleus and in so doing spread out, some forward, some backward, thus forming a fan. Their collective position is at right angles to that formed at their entrance and parallel to the longitudinal fissure. The main group of arteries spreading forward cluster about one main vessel, the recurrent artery. They described branches of this artery going to the inferior surface of the lentiform nucleus, lower anterior portion of caudate nucleus, putamen and internal capsule, through the caudate nucleus to the external capsule.
Two of the earliest investigators of these vessels were Heubner (1874) and Duret (1874). Others in a later period include Carpenter, Noback and Moss (1954) who made a survey of anterior choroidal arteries in adult human brains. They report the anterior choroidal artery originates from the internal carotid artery in 76,6% of these cases, from the middle cerebral 11.7$, from the posterior communicating artery 6.7$ and from the junction of the anterior and middle cerebral arteries in 3«3$*
In 1.7$ the anterior choroidal artery was absent. In 90$ it was the first branch given off after the posterior communicating artery. The hypothesis is presented that the anterior choroidal artery is not an end artery, and that the posterior limb of the internal capsule receives as well as blood from the anterior choroidal artery, additional blood from the posterior communicating artery by means of anastomoses.
The second field of endeavor involves the morphology of the embryonic development of the forebrain blood supply. Evans gave an account of the head arteries in the Keibel and Mall Manual (1912) based on MaH*s work (1905) and others. Streeter (1918) described the underlying principles in the formation of the cranial vascular system and the adjustment of the blood vessels to growth changes in the brain and environment. He was chiefly concerned, however, with the development of the drainage channels, in particular the dural sinuses. Congdon (1922) described the evolution of the aortic arch system, including significant features in the origin of three cerebral arteries, the carotid, the basilar and the vertebral. Paget (1948) supplemented these fundamental studies with seven stages in the embryonic configuration of the arteries of the entire head region of the human, with particular reference to the embryonic transformations of the ophthalmic artery, the stapedial artery and the primitive trigeminal artery. She used graphic reconstructions of twenty- two sectioned embryos from 3 nan. to 40 mm., C-R length (when the primitive internal carotid artery appears to when the definitive adult origin of essentially all the cranial arteries is established)• Paget did not elaborate the origins of the medial striate artery or the anterior choroidal artery, nor did she stress the relationship of Embryonic blood vessels to the developing nucleij nevertheless her work was used as a basis for the present study as far as embryonic blood vessels were concerned.
Bremer (1943) did a similar study of human Embryos from 5 mm. to 40 mm. in an effort to explain, from an embryonic point of view, congenital aneuiysms of the cerebral arteries. In relation to Heubner 1 s artery, he stressed the change in direction of the course of the artery in relation to the growth of the hemisphere. In the embryo the artery ran laterally and even anteriorly. With the growth of the corpus callosum and the frontal lobe, the anterior perforated space is left far behind and the direction of the artery is reversed. He stressed the fact that the cerebral arteries are evolved from a capillaiy plexus arising from the earliest branch of the primitive aortic arch which runs along the underside of the brain.
The third field of endeavor in the study of the forebrain involves the morphology of the embryonic development of the forebrain nuclei. Streeter (1942) presented a bare outline of major nuclear developments In stages from 13 somites to 20 mm., CR length, for purposes of identification only. He stressed that the rostral end of the brain matures by 30 mm. and that this line of demarkation could be used to change from embryo to fetal terminology. Keith (1948) adequately dealt with the embryonic development of cerebral centers, but because his work also involved a large amount of comparative study, his work is more adequately covered in that context. In particular, his concepts of the development of th© caudate-thalamic stalk and of the velum interpositum were used as a basis for the description of these structures in the present outline. Both Shaner 5 s (1936) and Kodama ! s (1926) drawings were used to gain a concept of the development of the definitive caudate nucleus from the primitive striatum. Gilbert (1935) did a comprehensive outline of the embryonic development of the nuclear configurations and fiber tracts of the human diencephalon from the 9 mm. stage to the 39 mm. stage. She divided the diencephalon into epithalamus, dorsal and ventral thalamus and hypothalamus, separated from each other ty the sulci dorsalis, medius and ventralis respectively. From the epithalamus develops the habenular body. From the dorsal thalamus develops the anterior, medial, lateral and ventral thalamic nuclei, the medial geniculate body, the pars dorsalis of the lateral geniculate body and the pretectal region.
From the ventral thalamus develops the pars ventralis of the lateral geniculate bocfer and the reticular nucleus. In the hypothalamus there develops the preoptic region, the hypothalamic nuclei, the mammilaiy nuclei and the corpus subthalamicum.
Hamilton and Boyd (1952) was used as a rough guide in the development of the morphology of the caudate nucleus in the human embryo.
The fourth field of endeavor in the study of the forebrain is a comparative study and is outlined below as such under a separate heading.
Comparative Anatomy of the Forebrain Blood Supply
There is probably no region of mammalian anatomy which better represents Hackel's biogenetic law that ontogery repeats phylogeny than does the brain. During the development of the mammalian brain, however, phylogenetic stages tend to telescope, so as to meet the functional needs of the embryo. As a result, primitive features may co-exist with more advanced structures. Herrick (1930) outlined the course of vertebrate evolution, in relation to brain nuclei, in that the highest center of physiological dominance within the brain, that is, the most effective control of behaviour, has moved progressively forward from the mid-brain (most fish) to the thalamus and corpus striatum (reptiles and birds) to the cerebral cortex (mammals). Mary workers have contributed significantly to this outline. Hines (1922) outlined the growth and differentiation of the telencephalon from Sphenodon to man. Johnstone (1923) outlined the same development in terms of the caudate nucleus and stria terminalis.
The principle of vascular constancy throughout this evolutionaiy process was first stated as a law ty Buret (1874) , later reaffirmed Ty Shellshear (1930) and adequately worked out ty Abbie (1934). This principle states that the arteries, together with the brain, constitute a functional unit, a neurovascular mechanism in which neither component is independent of the other. This led Shellshear to state that arteries are constant in their terminal supply and that any change in brain structure is reflected in an equivalent alteration in its blood supply.
Study ovi a.
Abbie completed a phylogenetic series of the adult brains of vertebrate phyla from Fishes to man, excluding Birds. The basic morphology of the forebrain arteries of higher animals is developed in the Fishes and Reptilia and reach their highest form in the higher Mammalia.
The basic stem upon which the series is based, including higher mammalian forms, is the internal carotid artery and its division, at the level of the hypophysis, into a cranial and a caudal division. Between these two divisions is developed the future circle of Willis. The caudal division, with modifications, is always continuous with the basilar artery. The anterior division undergoes extensive modification from the simple morphology found in the fishes to the extensive arteries of the forebrain found in man.
In Fishes the anterior division is developed in relation to the olfactoiy apparatus A consists of a more highly developed, more primi tive, ventral palaeo-olfactorium and a dorsal neo-clfactorium. The ventral part contains, among other structures, the cortex of the tuberculum olfactorium and the palaeo-striatum. Johnstone relates the stria terminalis as a mass which connects this anterior olfactoiy area with the primitive amygdaloid complex. It lies in the ventricular part of the ventrolateral wall of the lateral ventricle and is the deep portion of the lateral, olfactoiy area. The bed of the stria terminalis includes part of what is known in human anatomy as the head of the caudate-putamen nuclei and their connections with the tail of the caudate. The caudate nucleus (exclusive of the stria) does not appear in Fishes but makes its first appearance in the primitive reptiles derived from the hypopallium of the neo-olfactorium. The bed of the stria terminalis is separated from the caudate ridge ty a deep ventricular groove. In mammals the two bodies come together in such a way that a continuous mass is formed.
The dorsal part, or neo-olfactorium, contains a lateral olfactoiy tract that develops into a lateral pyriform lobe and cortex, and medially the hippocampus and other structures. Inferior to the pyriform lobe, lying between this lobe and the palaeo-striatum, is the hypopallium which relates these regions to each other. This is the ventricular ridge out of which Johnstone states will be developed the neo-striatum.
The anterior division of the internal carotid artery passes cranially over the otpic chiasma and divides into two branches, the lateral and medial olfactory arteries, which run along the medial and lateral borders of the palaeo-clfactorium to its anterior aspect. By anastomotic channels, anteriorly as well as dorsally and ventrally, these vessels form a closed network which holds the entire hemisphere in its meshes. The grooves in which the lateral and medial olfactory arteries lie separate the neo-olfactorium from the palaeo-olfactorium, and the groove of the lateral olfactory artery persists in the higher forms, with modification, as the endorhinal fissure.
The lateral olfactory artery supplies the lateral part of the palaeo-olfactorium and the primordium of the hypopallium, pyriform lobe and most of the hippocampus. The medial olfactory artery reaches the medial part of the palaeo-clfactorium, the paraterminal region and the medial part of the primordium hippocampus.
In the Amphibia the carotid stem remains the same but the anterior division has undergone modification. The hemisphere has grow posteriorly over the diencephalon and the lateral olfactory artery has shifted its origin as a direct branch of the internal carotid to an origin closer to its field of supply and now arises from a diencephalic artery which in turn originates from the anterior division of the internal carotid. The lateral olfactory artery is now composed of three main branches corresponding to its relative field of supply. The main branch of the lateral olfactory artery is a pyriform branch, the second is a hippocampal branch and the third is a striate branch which persists in the endorhinal fissure and therefore is the true representative of the lateral olfactory artery in Fishes. This latter vessel^ anastomoses anteriorly with branches of the medial and lateral olfactory arteries around the tuberculum olfactorium and this primitive network, in one form or another, is maintained throughout vertebrate evolution. As the neo-olfactorium grows in importance so the lateral olfactoiy branches take over this field of supply, retaining a few palaeo-olfactoiy branches.
The medial olfactory branch relates more closely to the palaeo- olfactorium and remains relatively unchanged except that the growth of the hemisphere has displaced this artery ventrally to lie at the ventral-medial border instead of the medial equatorial groove. This artery supplies the medial part of the palaeo-olfactorium as well as some aspects of the lateral portion of the palaeo-olfactorium due to the shift in position. This means that the ventral aspects of the palaeo-striatum and primitive anygdala are supplied from the medial olfactory artery, while the lateral olfactoiy artery, through the striate branch, retains its distribution to the dorsal aspect of these masses.
In the Reptilia, as represented by Sphenodon, the brain and its arterial supply remain the same. The forebrain can still be divided into a palaeo-olfactorium and a neo-olfactorium, the former consisting of the tuberculum olfactorium, paraterminal body and palaeo-striatum. The neo- olfactorium includes the well developed hippocampus, pyriform lobe and hypopallium, the latter subdivided into an anterior hypopallium related to the general cortex and a posterior hypopallium related to the pyriform cortex and the anygdala. In Reptilia there appears the primordium neo- palli lying anteriorly on the dorsolateral aspect of the hemisphere interposed between the hippocampus and the pyriform lobe.
The carotid stem with its cranial and caudal divisions remains the same. The anterior division of the internal carotid, in Reptilia, consists of four main branches; (1) The posterior cerebral artery which arises near the origin of the cranial division. (2) The inferior cerebral artery of Dendy which arises near the posterior end of the endorhinal fissure, (3) The middle cerebral artery. (4) The anterior continuation of the cranial division^constitutes the anterior cerebral artery.
The posterior cerebral artery in Reptilia represents the hippocampal artery of the frog which is a branch of the lateral olfactory artery in this animal. The original stem of the lateral olfactory artery persists in Reptilia only as an anastomotic channel between the posterior and middle cerebral arteries. The origin of the posterior cerebral artery again has been shifted posteriorly along with the posterior expansion of both telencephalon and diencephalon. A still more posterior diencephalic artery has been employed as the most convenient stem. It now supplies nearly all of the hippocampal formation, the posterior portion of the paraterminal body, as well as the choroid plexus of the third and lateral ventricles.
The middle cerebral artery is closely related to the endorhinal fissure and supplies the pyriform lobe and lateral part of the palaeo- olfactorium as well as the whole of the hypopallium and dorsal part of the palaeo-striatum. Therefore, its main trunk represents both striatal and pyriform branches of the lateral olfactory artery of the frog and all of the lateral olfactory artery of the dogfish. The middle cerebral artery ends in a general anastomosis over the primordium neo-palli.
The anterior cerebral artery is the descendant of the medial olfactoiy artery of Fishes and Amphibia, but in lower forms the medial olfactoiy artery passes to the olfactoiy stalk while in Reptilia the greater part of the blood stream is diverted to the medial wall of the hemisphere; that is, to the paraterminal body, the anterior portion of the hippocampus and the new general cortex. The old channel is indicated ty small branches which run anteriorly along the medial border of the palaeo- olfactorium to the olfactory stalk.
The inferior cerebral artery of Dendy which is peculiar to the Sphenodon, passes dorsally between the hemisphere and the optic tract to reach the posterior portion of the corpus striatum, i.e., the primitive anygdala and the associated part of the palaeo-striatum. It j'kegctkerrti&ith an anastomotic chain between the cranial division of the internal carotid artery and the posterior cerebral artery is, therefore, the primordium of the choroidal artery system of the Mammalia and will be discussed under a separate heading.
In the Mammalia the description of the brain falls into two subgroups, the Sub-primates and the Primates. The forebrain of the former represents an enormous expansion of the neo-pallium causing a secondaiy deformation of the cerebral hemispheres. The palaeo-olfactorium has maintained its original position and the neo-olfactorium has developed around and above it. The primordium neo-pallium has appeared between the hippocampus and the pyriform lobe and by its expansion has pushed the latter structures ventrally and medially. Associated with these changes are the appearance of the corpus callosum, the breaking through of the internal capsule and the consolidation of the basal ganglia. In particular, the latter means the junction of the neo-striatum with the palaeo-striatum.
The anterior superior head of the caudate nucleus, the bodies of the caudate and putamen nuclei, which are derived from the hypopallium, join the anterior inferior head of the caudate-putamen mass, the globus pallidus, the tail of the caudate and amygdaloid nucleus; the latter derived from the palaeo-striatum. Also, in consequence of the dorsoposterior expansion of the hemisphere, the pyriform lobe becomes bent upon itself which is accompanied by a bending of the endorhinal fissure. The anterior and posterior parts of the endorhinal fissure come to lie almost parallel with each other.
This is significant in the development of Heubner's artery.
The arterial supply to the brain is similar to lower forms in that they retain their old origin and field of supply, they have become modified to deal adequately with the greatly increased demands made upon them. The internal carotid stem divides, alongside the hypophysis, into cranial and caudal branches; the cranial division passes anteriorly over the optic tract while the caudal division runs posteriorly to join the basilar artery as before. The posterior cerebral artery no longer arises from the cranial division, for as the phylogenetic scale is ascended the artery arises from successively posterior positions until it receives the bulk of its blood from the basilar artery. It supplies most of the hippocampus, the posterior parts of the inferior, medial and lateral surfaces of the hemisphere, a portion of the tail of the caudate nucleus and the anterior part of the mid-brain.
The middle cerebral artery arises from the stem of the internal carotid artery and runs in the posterior endorhinal fissure and at its lateral angle, makes use of the old pyriform branches, crosses the pyriform lobe to reach the lateral aspect of the neo-pallium which it supplies. Small branches in the anterior endorhinal follow the old course to the olfactory bulb and supply the lateral parts of the palaeo-olfactorium and bulb. The artery supplies most of the pyriform lobe, the anterolateral aspect of the anygdaloid nucleus, a portion of the striatum and most of the lateral aspect of the general cortex. The small continuation of the middle cerebral in the anterior endorhinal fissure supplies striatal branches, arteries to the pyriform cortex, and palaeo-olfactorium and anastomotic branches to the anterior cerebral artexy over the palaeo- olfactorium. These branches finally pass on to the lateral aspect of the olfactory bulb where they end by joining anterior cerebral branches.
Therefore, the stem of the middle cerebral artery, in Subprimates, is the same in origin and in course as its predecessor in Heptilia, and its proximal trunk, closely related to the posterior endo-rhinal fissure, has only altered in size® In Reptilia the main course of the artery is along the endorhinal fissure to the olfactory stalk while the pyriform branches are secondary; in mammals the main trunk of the artery leaves the endorhinal fissure at its lateral angle and traverses the pyriform lobe to reach the neo-pallium® The artery still supplies the whole of the hypopallium, dorsolateral aspects of the palaeo-etriatum and primitive auygdala; in Primates it reaches the superolateral part of the head of the caudate-put amen mass, the claustrum, the putamen and body of the caudate nucleus, the anterolateral aspect of the amydaloid nucleus and the lateral one-third of the globus pallidus.
The anterior cerebral artery is the forward continuation of the cranial division of the internal carotid artery, passing forward to the medial border of the palaeo-olfactorium, where it joins its fellow of the opposite side, then ascends over the front of the corpus callosum and then runs posteriorly to anastomose with hippocampal branches of the posterior cerebral artery® This is merely an extension of the course of the homologous vessel of the Reptilia due to the stretching of the anterior part of the hippocampal formation by the growing corpus callosum. As in Reptilia, the primitive course along the medial palaeo-olfactorium is maintained by small branches which reach the medial aspects of the olfactory bulb and anastomose with branches representing the primitive anterior course of the middle cerebral artery.
From both the main stem of the anterior cerebral artery and its forward continuing branches, twigs are given to the medial part of the palaeo-olfactorium. Some branches enter the base of the brain to the ventromedial head of the caudate-put amen mass and ventroanterior limb of the internal capsule. The main trunk supplies the paraterminal body, supra-callosal hippocampus and its anterior share of the cortex. Since the anterior cerebral artery supplies the medial and anterior part of the palaeo-striatum in Sphenodon, and the homologous vessel, in mammals, supplies the anteriomedial part of the head of the caudate-putamen mass as well as the anterior medial part of the globus pallidus, it appears that the latter structures have evolved from the former areas of the palaeo- striatum. In Mammalia the lateral striate branches of the middle cerebral artery enter the endorhinal fissure and pyriform cortex to pass to the body of the caudate nucleus. Anteriorly these arteries supply the dorsolateral head of the caudate-putamen mass.
The anterior choroidal artery takes origin from the cranial division of the carotid artery, runs posteriorly along the optic tract and ends by anastoroosing with the posterior choroidal artery over the lateral geniculate bociy. It supplies part of the pyriform cortex, part of the amygdaloid nucleus and most of the tail of the caudate nucleus, branches to the optic tract, lateral geniculate body, part of the hippocampal formation and choroid plexus, the posterior inferior limb of the internal capsule and globus pallidus.
In Sphenodon there is no artery homologous with the anterior choroidal artery i.e., there is no single vessel which arises from the cranial artery, passes posteriorly along the optic tract and ends in the caudal artery. Here the future choroidal artery is represented ty two primordial conditions: (l) The inferior artery of Dendy, taking origin from the cranial division, passes dorsally between the optic tract and the cerebral hemisphere, giving branches to the optic tract and finally to the corpus striatum, (2) There is an anastomotic vessel betveen the middle cerebral and caudal artery vhich crosses the posterior inferior angle of the hemisphere, giving branches to the amygdaloid region and to the optic tract. The fusion of these in high^reptiles (crocodiles) results in the anterior choroidal artery, vhich, in this animal does arise from the cranial artery, runs posteriorly along the optic tract and ends ty joining the caudal artery. It here supplies the optic tract, underlying geniculate body, amygdaloid nucleus and posterior part of the corpus striatum and anastomoses with the posterior cerebral artery.
There is as yet, no branch to the choroid plexus, and it is interesting to compare this vith the early 12,5 mm, stages of human embryos. The anterior choroidal artery, in this stage, is nearly as outlined for the higher Reptilia and has no branch to the choroid plexus. In these higher forms the hemisphere bulges backward and draws the lateral ventricles in an arcuate form between the foramen of Monro and the amygdaloid nucleus. The choroidal artery branches come to lie alongside the lengthened choroid fissure and supply more collateral twigs to the plexus. At the same time the posterior branch from the caudal artery (the posterior choroidal artery) comes to supply more of the choroid plexus. This is the primitive mammalian form. In ascending the mammalian scale, the anterior choroidal artery has progressively devoted more and more of its blood to the choroid plexus, until in apes the anterior choroidal artery is equally divided between the plexus and its union with the posterior choroidal artery over the lateral geniculate bocfcr. In man, the artery supplies the optic tract, anygdaloid nucleus and an anastomosis over the lateral geniculate body biit its main trunk is devoted to the choroid plexus.
Thus, in the Primates, the change is one of degree only, as the acquisition of the neo-pallium and corpus callosum is the largest change featuring the mammalian brain. The arteries in their pattern, course and distribution, are fixed with exception of increased supply to the enlarged neo-pallium. The palaeo-olfactorium and neo-olfactorium have been thrust away to the basal and medial surfaces of the hemisphere but receive the same blood supply they have always had.
The bending of the endorhinal fissure has caused the anterior and posterior portions to lie almost parallel so that the anastomoses around the palaeo-olfactorium become crowded and only one anastomosing channel is retained. It receives nearly all of its blood supply from the anterior cerebral artery and its connection with the middle cerebral is reduced to a rudiment. The persisting channel is Heubner’s recurrent artery and, as such, is a persistent form of the most primitive cerebral vascular network. The possibilities of variation in its course and origin are numerous and depend upon which anastomotic channel is used. The artery may arise early or late from the anterior cerebral artery depending upon whether the anastomotic channel used was anterior, middle or posterior. Variations in course depend upon the same factors and the artery may cross the palaeo-olfactorium anteriorly, posteriorly or in an intermediate course, or in a combination of all three. Whatever its course and origin, Heubner’s artery always supplies the anterior cerebral field and variations of its total area of distribution depend upon how much of the middle cerebral field it has taken over and how much left for the middle cerebral artery to supply.
The bending of the endorhinal fissure has a further significance in that as the fissure becomes more flexed as the phylogenetic scale is ascended, the striate branches at the angle enlarge and those at the medial end dwindle. The concentration of a great number of arteries at the base of the internal capsule, greater than in apy other part of the brain, explains why this has been called the site of election for cerebral hemorrhage. The chances of arterial rupture here are at least twice as great as ary where else.
- In Fishes, the forebrain is composed mainly of a palaeo-oifactorium which is enveloped in a closed network of arteries. Two main channels run in grooves separating the palaeo-olfactorium from the neo- olfactorium.
- The common ancestor of Amphibia and Reptilia possessed separate anterior, middle and posterior cerebral arteries but the Amphibia hslteonly medial and lateral olfactory branches. The medial is the same as in Fishes but the lateral has shifted to arise from diencephalic vessels and is now composed of three sets of branches, hippocampal, pyriform and striatal.
- Reptilia have separate anterior, middle and posterior cerebral arteries from the network. The anterior cerebral artery has developed from the medial olfactory artery but its main stream has been diverted to the medial wall of the hemisphere. The middle cerebral artery represents the combined pyriform and striatal branches of the lateral olfactory artery of the frog, but with a direct connection with the cranial division of the internal carotid artery. The posterior cerebral artery has arisen from the lateral olfactory artery and is devoted mainly to the hippocampal region.
- In lover mammals the cerebral arteries cope with the growing neo-pallium. The dorso-posterior expansion of the hemispheres has caused the posterior cerebral artery to employ successively posterior stems of origin until it receives its blood from the basilar artery, which enlarges, and still supplies most of the hippocampal formation plus its share of the neo-pallium.
- The anterior choroidal artery has evolved from the inferior cerebral artery of Sphenodon plus anastomotic channels with the posterior cerebral artery. The middle cerebral artery sends most of its blood to the pyriform lobe and neo-pallium but its old course and distribution in the anterior endorhinal fissure are subserved by small branches running forwards to the olfacfcoiy bulb. The anterior cerebral artery sends most of its blood to the medial wall and anterior cortex.
- The evidence of the blood supply indicates the hypopallium has given rise to the body and superior head of the caudate nucleus, putamen, elaustrum, and the anterolateral part of the amygdaloid nucleus. The palaeo-striatum has formed the ventromedial head of the caudate- putamen mass and the globus pallidus. The primitive amygdala forms the posterior medial part of the amygdaloid nucleus and the tail of the caudate. The vascular supply of the various parts of the basal ganglia is constant from Fishes to man.
- Heubner's artery is the survivor of the anastomosis over and around the palaeo-olfactorium, one channel remains large, drawing its blood supply from the anterior cerebral artery but retaining its old connection with the middle cerebral artery in rudiment&iy forms. It supplies most of the palaeo-olfactorium and the inferomedial part of the head of the caudate- putanen mass and the anterior part of the globus pallidus.
From this picture of comparative blood supply, Abbie has derived certain principles which govern the formation of cerebral arteries:
- Functional constancy — whenever a neural mechanism evolves, an artery develops for its supply and this neuro-vascular relationship remains constant throughout evolution.
- Econony of distribution — wherever two or more end arteries lie close together, they employ a common vessel of distribution.
- Convenience of source — if a distributing channel becomes separated from its source it obtains blood from a nearer source by enlargement of existing anastomotic channels.
It is upon these principles that the following account of the development of blood supply to the basal ganglia in the human embryo is based.
Methods and Materials
Human embryos were chosen for study. A series of over fifty embryos ranging from 12 mm through 50 mm, C-R length, was obtained from the hospitals of the city. Of these, thirty embryos were judged to be in good enough condition and were drawn to scale and processed as outlined below. These were subsequently divided into seven groups depending upon their crown-rump length, at 9 mm, 12 mm, 15 mm, 20 mm, 25 mm, 30 mm, and 40 mm. Each group was supplemented by embryos from the human Embryo collection of the Anatomy Department of the University of Alberta.
Of the original series, only a veiy small number were found, after processing, to be in good enough condition for reconstruction purposes. The loss of Embryos was explained in part ty the following factors:
- The extreme rapidity of disintegration of brain tissue in the Embryo and the indeterminate period of inter-uterine death of many of the Embryos in cases of natural abortion.
- Experimentation needed to develop the technique for adequately processing human Embryos, particularly the Embryos in the larger size range.
A number of different procedures was employed:
- For study of human Embryos ranging from 10 to 40 mm., C-R length, use was made of the Anatomy Department for serial sections. The Embryos, mostly cut at 10 micron, are stained with haematorylin and eosin. Twenty-five of these were studied and drawn on the camera lucida for quick sketch reconstructions.
- Eighty class sets of serial sections of pig Embryos from 10 to 12 mm in length, cut at 12 micron were also examined. These furnished information regarding the forebrain arteries and possible examples of abnormal morphology being developed in the embryo.
- Injection methods did not prove satisfactory with human Embryos as it is necessary to obtain them before not more than two hours has elapsed since death. After this time clots form in the vascular tree preventing free circulation of injection fluid. Also, the immediate placing of Embryos in 10% formalin, in the operating room, hardens the vessels and allows for considerable leakage. The injection fluid used was diluted India ink. Injection apparatus was both drawn glass canulue and drawn plastic tubing. These were connected ty tubing to an elevated flask, the whole system being filled with injection fluid* The tip of the left ventricle was cut off and the canula was inserted through the ventricle, through the aortic valve and into the ascending aorta, where it was tied into place* A drainage tube was tied into place in the superior vena cava* The descending aorta was tied off* Gravity pressure was augmented when needed by positive pressure applied to the upper flask* This method proved successful for a small number of larger Embryos over 40 mm. in size, but was abandoned for the main range of Embryos for the reasons stated above.
- The Gormi method was employed for the visualization of alkaline phosphatase in the endothelium of the Embryonic blood vessels of the brain. This method was not used because it often selectively brings out the c&pillaiy structure which is not wanted and does not stain the venous system, which is desired*
- The Champy-Kull method of staining for contained blood was employed. The blood corpuscles are strikingly differentiated from the other tissues. This method would give good results in the Embryo and is not difficult but it is necessary that the vessels contain blood and that the corpuscles be well fixed with no loss of haemoglobin during fixation. If either of these requirements is not carefully controlled the method will fail* For fixation 10% formalin gives good results and embedding in celloidin is preferable because it prevents the corpuscles from being washed out* Because of the difficulty in controlling the blood content of embryo blood vessels and the variability- in fixing -whole embryos, a simpler staining method -was decided upon.
- Various stains were experimented with in order to discover the best differentiation of blood vessels from the surrounding tissue. Some of the stains tried were:
a. Giemsa’s stain for blood vessels, May-Grunwold modification.
b. Giemsa’s stain - ¥alback*s modification.
c. Aqueous alum haematoxylin.
d. Maximov's stain.
e. Jenner's - Geimsa.
f. Mallory’s phosphotungstic acid haematoxylin.
g. Azure haematoxylin and eosin.
h. Delafield’s haematoxylin with eosin I counter stain.
The last named stain was found to be the stain of choice for demonstration of both blood vessels and ganglion centers.
Preparation of Embryos
The embryos were usually received in 10% formalin solution. The quantity of solution was adjusted to at least twenty times the volume of the embryo which was then left to fix from twenty-four hours to one week, depending on the size. The embryos were then washed in a slowly running stream of water for twenty-four hours, transferred through an alcohol series running from 30% to absolute alcohol, then butyl alcohol and wax mixtures (50-50) in an oven at 56°G. The melting point of the wax is 52-54° Ca The embryos were then vacuum infiltrated in three wax changes from two to twelve hours each, depending on size and embedded by means of metal moulds.
Sections were cut in coronal plane, serially, at 15-30 u, mounted with egg albumen and dried over night in a drying oven. Sections were immersed successively in sylol, absolute alcohol and diluted cell- oidin for one to two minutes and then drained. The membranes were hardened subsequently by dropping the sections into 70% alcohol, followed by a wash in distilled water. The sections were then transferred to staining solutions which consisted of haematoxylin solution for one to five minutes, washed, and counterstained with eosin Y (1%) for six minutes. The sections were washed quickly, dehydrated through successive alcohol changes to xylol and mounted in piccolyte. The results gave nuclei bright blue and cytoplasmic structures red. The differentiation of the blood vessels was made on slight differences in color, contained blood and morphology.
Celloidin embedding methods, both fast and slow, were tried; also wax-celloidin combinations for embedding were employed in an effort to gain greater structural support, with serial sections still possible. However, these methods usually resulted in too much shrinkage of the brain tissues.
Methods of Reconstruction
The lateral, graphic reconstruction method from serial sections was used for three dimensional visualization of the developing centers.
An accurate outline of the embryo was made representing it in the point of view to be used for reconstruction and enlarged to the precise scale upon which the reconstruction was to be made. This drawing was made before the embryo was embedded but after dehydration with alcohol. It was further necessary to know accurately the plane of the cut and the thickness and the total number of sections in the series. The plane of the section was determined by a study of the sections, determining what section passed through two reference points and referring these reference points to the outline drawing. By knowing the total number of sections and at what thickness they were cut, a grid was established wherety each line represented the plane of a selected section. The outline drawing was projected, at the scale of reconstruction upon this grid, making the plane of section, determined above, parallel to the grid.
The outline of the actual sections corresponding to the numbered lines in the grid was now made with the camera lucida® Every tenth section was sketched to scale on the camera lucida, each sketch then representing a region 150-300 u thick, depending on the original thickness of the cut. From the camera lucida drawings of the single sections the measurements were taken to fix the position of the organs in the reconstruction. For a given section the exact position in the reconstruction was fixed by the line on the outline drawing of the ei- bryo corresponding to the number of the section. On the drawing of the section the distance of the organ to be reconstructed from the point in the section corresponding to the outline of the embryo was measured off and then marked upon the proper line of the reconstruction diagram. In this way a succession of dots was obtained which marked the outline of the nuclei. These dots were then connected ty a continuous line which indicated the form and correct position of the organ. These outlines were variously shaded to represent depth. The arteries were shaded in red and the veins in blue and these vessels were dotted to represent a medial position to a structure where applicable. The corpus striatum was represented in black to show its morphology from a lateral position.
Embryos from 12 mm. to 33 mm were used as a series as it was considered this range covered adequately the conditions under study. The embryos from 12 mm to 25 mm were done at an enlargement of 40 diameters.
the 33 mm embryo alone vas done at an enlargement of 20 diameters. Photographic reproductions of the graphic reconstructions constitute trie main plates in each section. Additional plates reproduce enlarged areas of inportant regions vhich are outlined on the main plates. The figures are photographs of the original embryo sections representing the plane by vhich they are numbered.
Plate I represents the left half of the brain of a human embryo of 15.0 mm, C-R length with an estimated ovulation age of 37 days. It is a graphic reconstruction of the configurations of the nuclei forming the medial wall of the mesencephalon and diencephalon and the medial external wall of the anterior portion of the left cerebral hemisphere. This graphic reconstruction was done to provide a basis to which the series of embryos could be related, and was constructed ty serial cross sections. The term nucleus as used in these descriptions does not necessarily indicate a region directly comparable to a nucleus in the adult sense, but indicates an area of cellular concentration which can be identified in the forebrain of successively older embryos. The names given to the tracts and nuclei have been based on the names of corresponding nuclei and tracts in the adult brain wherever it has been possible to identilNr the embryonic structure with its adult derivative.
Terms indicating position in the forebrain are based on the morphological axis of the brain.
The brain is a thin walled tube easily divided into the five brain vesicles, outlined in this series ty the mid-line cut edge. The roof plate is thin in the telencephalon and myelencephalon, but thicker in the mesencephalon and diencephalon. The floor plates of the mesencephalon and rhombencephalon show their characteristic thickening and the pontine flexure is well accentuated.
The telencephalon medium is the floor of the great longitudinal fissure dividing the anteriorly and superiorly expanding cerebral hemispheres* It outlines the anterior end of the diencephalon and its connection with the cerebral hemispheres, and is subdivided into a ventral lamina terminalis and a dorsal thin portion, the choroidal area* These latter two regions are again subdivided into two regions. The lamina terminalis is divided into a massive anterior part, -which contains the primitive anterior commissure (A.C.), and a posterior portion which contains the large optic chiasma (O.C.). These portions of the lamina terminalis are separated try the optic groove (O.G.) which is continuous posteriorly with the optic recess (Q.R.). The anterior part subsequently develops dorsalward to replace the thin choroidal connection between the hemispheres with the future corpus callosum.
The dorsal thin portion, the choroidal area or velum interposition! is subdivided into an anterior portion in the roof of the foramen of Monro and a posterior portion in the roof of the diencephalon. The anterior region presents as a sharp longitudinal ridge over the roof of the large foramen of Monro extending laterally into the lateral ventricles. In future development the two lateral choroid plexuses enter from this ridge. It is impossible to draw the dividing line between the anterior portion and the posterior portion. The latter presents as an arch posteriorly along the roof of the diencephalon as far as the posterior commissure (P.C.). The development of the velum interpositum holds the key to the development of the choroid plexus branches of both the anterior and posterior choroidal arteries as well as the superior venous drainage of the telencephalon and diencephalon.
The metencephalon consists of the prominent cerebellar plate (C.P .) which is separated from the mesencephalon by a marked constriction in the total brain tube, the isthmus. The mid-brain collicular plate (Co.P.) is rapidly expanding posteriorly to form an extending lip over the underlying metencephalon. Both collicular and cerebellar plates lie superiorly to a continuous groove extending from the spinal cord forward into the diencephalon as far as the optic recess (O.R.). This groove, the sulcus limitans, marks the rapidly developing dorsal sensoiy plate from the slowly thickening ventrolateral floor, the forward extension of which is the tegmentum (TEG). Above the sulcus, forming the posterior region of the diencephalon, is the developing pretectal region (PTE) contiguous with the posterior commissure in the roof. This region and the habenular nucleus together form the epithalamic region which is divided from the dorsal thalamus ty a groove, (the dorsal thalamic sulcus) (S,D,TH,), that runs superiorly from the sulcus limitans.
The forward continuation of the sulcus limitans, the shallow ventral thalamic sulcus (S.V,TH.), divides the diencephalon into a larger superior portion (the dorsal (D,TH.), and ventral (V,TH.), thalami, and an inferior smaller area, the hypothalamus. At this stage the dorsal or optic thalamus has begun its rapid development which from this time on will overshadow the more slowly growing ventral thalamus. From the posterior lateral region of the dorsal and ventral thalami will differentiate the pulvinar and dorsal nucleus of the adult lateral geniculate body, This latter optic nucleus in turn determines the original growth and subsequent development of both anterior and posterior choroidal arteries. The thick walled dorsal thalamus is separated from the ventral thalamus by a groove, the medial thalamic sulcus (S.M.TH,). Superiorly to this groove a cell free lamina appears, running in a dorsorostral to ventrocaudal plane thus separating the dorsal and ventral thalami. This lamina is called the zona intrathalamica (Z.IT•)
The hypothalamic floor extends, in the median plane, from the mammillaiy recess to the posterior end of the chiasmic plate. The future pars neuralis of the hypophysis has begun its invagination from this region, the preoptie region surrounds the optic recess (O.E.) and continues dor- salHy into the striatal ridge. The preoptic regions of the two halves are separated ty the lamina terminalis and are the regions in “which the supraoptic nuclei develop (S.O.N.).
Running dor sally from this region to the floor of the foramen of Monro is a ventricular sulcus separating the medial limb of the corpus striatum (C.S.) and the hypothalamus. Immediately dorsocaudal to the superior end of this sulcus lies the mid-region of the thalamus which now- forms the posterior boundry of the foramen. The dorsal boundiy of this mid-thalamic division can be followed anteriorly to the region of the velum interpositum. The floor of the foramen is formed ty the corpus striatum. This basal ganglion is not well defined in Embryos under 10 mm., C-R length. Development begins, from the 10 to 20 mm. stage, as a single ridge which soon divides into medial and lateral hillocks, divided ty the intrathalamic sulcus (IT.S.). Differentiation of adult caudate nuclear cells does not begin until the 40 mm. stage, beyond the scope of this stuc^-. At present the ganglion extends from the developing temporal pole to the lamina terminalis and anteriorly it extends into the olfactory ventricle, the medial hillock forming the lateral wall of this ventricle.
Johnston (1923) called this sulcus the strio-caudal sulcus, the medial hillock the ”bed of the stria terminalis” and the lateral hillock the caudate nucleus, although other authors have disagreed with him. It is clear that the corpus striatum has a close connection with the olfactory region of the cerebral vesicles as well as with the hypothalamus.
It is important to note the manner in which the cerebral vesicles are connected to the walls of the third ventricle and to each other.
The union of each cerebral vesicle with the other is illustrated in the above description of the telencephalon medium. At what may be called its posterior border, each vesicle is continuous with the optic thalamus while at its lower border it is continuous with the hypothalamic region. At both these borders it is the striate area which joins the hemispheres to the thalamic regions. Hence, the corpus striatum becomes the bond which links each cerebral vesicle to the diencephalon; it becomes the highway for the future internal capsule. This striate-thalamic junction may be looked upon as the stalk from which the cerebral expansion takes place. At this stage the expansion of the vesicles show only a frontal and a temporal pole but soon the expansion will have reached the mesencephalon in the form of an occipital pole.
The various regions of the cerebral hemispheres are well delineated. Anteriorly, a small olfactory area evaginates to form the olfactory vesicle (OLF. TUB.), later obliterated to form the definitive olfactory- nerve (Q.N.), bulb and tract. The medial wall of the hemisphere is composed of the paraterminal (septal) and hippocampal primordia (HIPPO.?.); ventrolaterally the floor is the striato-pyriform mass; between these is the pallial or mantle region in which the cortical centers, which makes up the great mass of the cerebral hemisphere, are being produced. On the medial wall of each vesicle, inferior to the hippocampus, is the thin undifferentiated secretory region.
PLATE I (H51, original 40X).
This is a photographic reproduction of a graphic reconstruction (a lateral view) of the forebrain of a 15.5 0=R length f human Embryo, as outlined in the text
Plate II is a graphic reconstruction of the nuclear configurations forming the medial wall of the mesencephalon and diencephalon of the right half of a 12.5 mm., C-R length, human Embryo's brain, with the left cerebral hemisphere and the arterial and venous systems of the left side superimposed. Reconstruction of this type was used in order to illustrate, in two dimensions, the three dimensional aspect of the erabxyo brain. Serial cross sections were used to reconstruct structures lying lateral to the medial wall, with special reference to the blood vessels. Some of these sections are photographically reproduced in Figures A1 to A10 and are labelled on plate II, on the left, as planes A-L. The numbering of these planes, on the right, refers to the original sections.
Plates III and IV are enlarged reproductions of the areas outlined on the onion paper on plate II.
Plate II: Both diencephalon and telencephalon show the same nuclear structure as depicted in plate I but in a less expanded state.
The expansion of the cerebral vesicles has commenced and the lateral ventricles are in wide communication with the third ventricle through the foramen of Monro. The posterior or temporal region is beginning to pass -backward and downward over the side and roof of the diencephalon.
The frontal region is bulging forward over the olfactoiy bulb, while the roof of the bean shaped vesicle is rising above the diencephalon leaving, between the right and left hemispheres, the longitudinal fissure. The future posterior expansion, the occipital pole, is not yet in evidence.
The cerebral vesicles are illustrated in cross section in figures A6 to A10. Each hemisphere consists of a thickened basal portion, the undifferentiated corpus striatum, a thinner supra-striatal pallium, the cerebral cortex, and a thickening medial wall, the hippocampus, continuous in a folded line with the thalamic wall of the diencephalon. The thinned area of medial wall directly inferior to the hippocampus, which will form the choroidal inflection, is not yet present.
The striatal region first appears at approximately the 12.5 mm. stage, as a projection of the base of the telencephalon into the ventricular cavity at the level of the foramen of Monro (figure A7)• This striatal bulge in the lateral ventricle is moulded with the ventricle, as the hemisphere expands laterally and posteriorly, into longitudinal ridges. In figure A7 the separation of the mass into the medial hillock and lateral hillock ty the intrathalamic sulcus (IT.S.) is beginning to appear. Anteriorly, the medial hillock, which is the bed of the stria terminalis, forms a prominent ridge which is the lateral wall of the olfactoiy ventricle (figures AS and A9)• Posteriorly there is only an indication of an extension of the striate mass to the temporal pole (figure A6). In this region the striate mass is continuous with the thalamic area of the diencephalon, extending to the preoptic region (PO.R), surrounding the optic recess. This striate-thalamic junction is a primitive one that is retained as the pathway ty -which the internal capsule cements the hemisphere to the diencephalon. This junction may be looked upon as the stalk, or hilum, from which the cerebral expansion takes place. Viewed from the ventricular side, the striate boc^r of each side appears to be a forward and lateral I"/
continuation of the thalamus. Viewed from the lateral side it appears to be a continuation of the base of the olfactoiy stalk. The slowly differentiating cortex of the striate body is the pyriform cortex. There is no indication of the internal capsule.
The corpus striatum, at this stage, represents the primitive mammalian structure. It is composed mainly of the medial hillock of palaeo-striatal origin which contains main connections between the olfactory region and the primitive auygdaloid region. Definitive structures developed in these regions include the inferomedial head of the caudate-putamen mass, globus pallidus, a portion of the amygdaloid nucleus and a portion of the tail of the caudate nucleus. Beside the medial hillock the slower developing lateral hillock appears as an ingrowth from the hypopallial area of neostriatal origin. This will eventually form the greater part of the definitive body of the caudate and putamen nuclei.
Other important nuclei which are exerting an influence on the morphology of the definitive forebrain blood supply, at this stage, lie in the diencephalon. These are particularly the dorsal and ventral thalami in which, in the posterior extension of the latter, the dorsal nucleus of the lateral geniculate bo^y is forming (figure A6). Extension of the optic tract to this bo<3y from the optic chiasma is not shown in these graphic reconstructions and is the predominate nuclear mass determining the course and area of distribution of the anterior and posterior choroidal arteries.
With exceptions, the essential mammalian pattern of the circle of Willis may be recognized as early as this 12.5 ism. stage. The anterior coimnunieating artery, the medial striate artery (Heubner®s recurrent artery) and the anterior and posterior choroidal arteries are either nonexistent or exist in a primitive premammalian form. It is interesting to note that the velum interpositum has not yet projected into the lateral ventricles to allow the formation of the choroid plexus and consequently no choroid plexus branches of the anterior and posterior choroidal arteries are required at this early stage* There is a definite laterally projecting ridge in the roof of the anterior foramen of Monro (figure A9) into which the velum interposition will subsequently invaginate, ¥hile the origin of most definitive arteries is distinct at this time, the final direction and relative size is yet to be determined ty further growth of the brain, in particular the gradual predominance of the cerebral hemispheres*
The internal carotid artexy (I.C,A,) branches above the region of the hypophysis into an anterior and a posterior division (figures A4 to A6). The morphology* of both divisions constitute a primitive mammalian condition. The posterior division, the posterior cerebral artery, which is a part of the caudal division of lower vertebrates, is primitive in that it is represented at this stage fcy its primitive roots, the dien- dephalic artery (D,A,) and the mesencephalic artery (M,A,) (figures A1 and A2). It is mammalian in that these 1 roots derive their main blood source from the basilar artexy (B.A,) and that this complex is joined to the internal carotid artexy by the posterior communicating artexy (P,C,A,) (figure A3), The latter artery represents the posterior tract of the posterior cerebral artexy complex as it receives its blood supply from diencephalic branches of the basilar artery progressively further from the internal carotid artexy a This has been a response to the posterior enlargement of the forebrain, shown in plate II as mainly the diencephalon and later due to the posterior enlargement of the cerebral hemispheres*
The main branch running anteriorly from the diencephalic root is the posterior choroidal artery (P,GH,A,) (figure A3),
The anterior continuation of the internal carotid artexy crosses the optic tract (not shown) and then gives off a superior and an inferior branch. The latter is the primitive ventral ophthalmic artery (P.V.O.A.), a large transitory artery of no significance in this pattern. The superior branch is the anterior choroidal artery (A.CH.A.) (figure A4).
The enlarged area illustrated in plate III shows the anterior and posterior choroidal arteries forming a closed loop of blood supply to the lateral geniculate area. In this the morphology is a primitive mammalian one. The vessels are mammalian and definitive in their site of origin in that the posterior choroidal artery is springing from the primordial roots of the posterior cerebral artery while the anterior choroidal artery springs from the anterior division of the internal carotid artery, much as both do in the adult human. As the medial cerebral artery expands, the origin of the anterior choroidal artery often shifts to this artery. The vessels represent primitive morphology in that thqy are composed of one main branch each and the main area of supply for both is the lateral geniculate area. The main branch of the anterior choroidal artery roughly follows the optic tract to this area. Plate III illustrates both arteries terminating around the lateral geniculate bo<^ under the fold of the temporal pole of the cerebral hemispheres (dotted termination of the anterior choroidal artery). There are no other major branches of these arteries indicated at this stage, nor ary indication of the development of the choroid plexus to which these arteries will provide major branches.
The posterior communicating artery, plate III, shows an interesting array of small branches to the hypothalamic region, ary one of which may enlarge to provide stems of origin of either anterior or posterior choroidal arteries or accessories to these arteries. Abnormal choroidal arteries will, consequently spring from the posterior communicating artery anywhere from the root of the anterior choroidal artery, as shown in plate III, to the root of the posterior choroidal artery on the stem of the posterior cerebral artery. The posterior choroidal artery, or its accessory arteries, may even spring from the basilar artery.
The enlargement shown in plate IV represents the anterior continuation of the internal carotid artery which divides at the margin of the cerebral hemisphere into a lateral and a medial vessel (figure A6). This morphology represents a primitive form that has been consistent throughout the phylogenetic series from Fishes. As in the Reptilia, the lateral branch is the middle cerebral artery (M.C.A.). As here represented, it is the main stem of the human definitive artery lying in its phylogen- etically determined course in the posterior endorhinal fissure. The pyriform branches of reptilian form, which will eventually become the main continuation of the artery beyond the endorhinal fissure onto the anterior lateral aspect of the cerebral hemisphere, are not yet developed to ary degree. The primitive anterior continuation in the anterior endorhinal fissure is not represented and is present only as a fine network of vessels joining with similar arteries from the anterior cerebral artery.
This network between the two cerebral arteries represents the original network around the palaeo-olfactorium and becomes important in the subsequent development of the medial striate artery.
The branches of the middle cerebral artery which are prominently shown in plate IV are only a graphic representation of a part of the lateral striate group (L.S.A). They are represented in their definitive form as fine vessels leaving the middle cerebral artery and dipping directly into the brain substance through the endorhinal fissure and pyriform cortex (figure A 7). The development of these arteries is in accordance with the phylogenetic principle that a developing nuclear mass will establish its blood supply from the most convenient source. In this case the underlying basal ganglia, the medial and lateral hillocks, are forming from both palaeo-striatal and neo-striatal origins. The blood supply to these regions established at this stage persist to the adult stage and in the latter stage the lateral striate branches of the middle cerebral artery supply the superior half of the head of the caudate — putamen mass, the horizontal boc^ of the caudate nucleus, the putamen, lateral part of the globus pallidus, and the superior half of the anterior and posterior limbs of the internal capsule. These striate branches, along with similar branches from the anterior cerebral vessels, supply the hypopallium and a large part of the palaeo-striatum. They represent analogous vessels from the lateral olfactoiy artery in Fishes, the striate and pyriform branches in Amphibia and the middle cerebral artery in Reptilia. Anterior and posterior projection of the basal ganglia will outgrow this original blood supply and in turn receive their blood from a more convenient source.
The medial branch of the anterior internal carotid artery is the anterior cerebral artery (A.C.A.) (Figure A6) which follows, as in lower forms, a medial course along the olfactoiy tracts to the olfactory tubercle and nerve. The portion of lateral striate arteries arising from the stem of this artery form a group with the similar branches from the middle cerebral artery. In this case they dip directly through the anterior perforated space to the underlying caudate head and adjacent hypothalamic region including the preoptic area. These two groups of striate arteries later will be joined by similar groups to form the centrally directed series of striate arteries; namely, (1) the striate branches from the anterior communicating artery to the head of the caudate-putamen mass, (2) the centrally directed branches of the posterior communicating artery, previously mentioned, to the underlying hypothalamus, and (3) the thalamogeniculate arteries from the posterior cerebral artexy to the dorsal thalamus and lateral geniculate bodies* In fact, the anterior and posterior choroidal arteries may •well be looked upon as specially developed branches of the latter two series.
At the thickened lamina terminalis, the anterior cerebral artexy splits into a medially directed branch to the laminal terminalis and a lateral primitive olfactoiy artexy. The former splits again into a small medially directed artexy to the future corpus callosum (M.A.C.C'.) and a lateral artexy to the lamina terminalis* This complex is forming a fine network of vessels across the midline with similar vessels of the opposite side and is graphically demonstrated in older embxyos as the primordal network of the anterior communieating artexy.
The laterally directed branch of the anterior cerebral artexy is the main continuation of this artexy and, as outlined for more primitive forms, is the primitive olfactoiy artexy (P.O.A.) • It lies first lateral* then medial to the olfactoiy nerve, to the nares and ends l y branching inferior to the olfactoiy tubercle of the cerebral hemisphere.
Summary of Arteries
The three principal arterial systems concerned are the choroidal system, the striatal system and the olfactoiy system. The choroidal arteries are established in their primitive form as major branches to the lateral geniculate body • No other adult branches are yet developed. The striate arteries from both the anterior and middle cerebral arteries already have developed into their definitive morphology and will be referred to only henceforth. The anastomosis between the middle and anterior cerebral arteries over the olfactoiy tubercle, which produces the recurrent artexy of Heubner is, as yet, in a primitive ill defined plexus. The primitivevregions of the basal ganglia have established their definitive blood supply, the never regions being developed will gain their blood supply as it is required,
At the 12.5 inm. stage (plate II) both telencephalon and diencephalon are drained ty the anterior plexus (Streeter 1913). The anterior sources of these drainage vessels lie both superiorly and inferiorly to the developing cerebral hemispheres. Inferiorly, the lateral striate veins drain the region of supply of the lateral striate artery system (figures A6 and A7) collecting to run directly into the anterior plexus from below. These vessels are the primordia of the definitive middle cerebral vein and as the striate veins are constant with the striate arteries, they are not represented and will only be referred to henceforth. Superiorly, the first indication of the superior sagittal sinus (S.S.S.) is beginning to form (figures A7 to A10) . Anteriorly, the vessels have formed a plexus across the midline which dips between the hemispheres. Only the larger channels are shown and between them is everywhere a fine anastomosing network. There is great variation in direction and pattern of these fine vessels. One or two larger channels drain upwards from the region of the lamina terminalis to join the plexus.
Figures A1 to A10 are photographic reproductions of cross sections of the original embryo at the planes labelled on plate II as well as beneath the figures.
Figure Al, plane C, demonstrates the relationship of the mesencephalic arteries (M.A.) to the mesencephalon and that of the superior artery brandies (S.C.A.) to the cerebellar plate (C.P.)•
Figure A2, plane D, represents a plane immediately superior to the floor of the mammilary recess of the diencephalon. The pretectum (PTE.) and tegmentum (TEG.) form the roof and floor of the mesencephalon respectively, while posteriorly the cut traverses the thickened floor of the rhombencephalon. The arterial pattern demonstrates the relationship of the superior end of the posterior communicating artery (P.C.A.) to the mesencephalon and the formation of the primordial posterior cerebral artery from the diencephalic and mesencephalic arteries. Posteriorly, ve find the basilar artery (B.A.) close in front of the floor of the hind brain, then the vertebral artery (V.A.) emerging anteriorly from the ventral surface of the spinal cord.
Figure A3> plane E, demonstrates a cut through the tip of the mamrflilaiy recess which picks up the origin of the posterior choroidal artery (P.CH.A.) from the superior end of the posterior communicating artery •
Figure A4* plane F, is a section through the posterior end of the diencephalon. The dorsal thalamus (D.TH.) is separated from the ventral thalamus (V.TH) Ty the zona intrathalamiea (Z.IT.). The hypothalamus (HY.TH.) forms the inferior walls and floor. The posterior communicating artery is a well defined branch lying lateral to this area. The posterior choroidal artery is at the level of the zona intrathalamiea. On the right is shown one of the well marked striate branches arising from the posterior communicating artery and running superiorly over the hypothalamus. Posteriorly, the basilar artery is forming a complex lying medial to the large fifth nerve (J N). The branches forming this complex are the origin of an abnormal artery sometimes found in the adult, running from this region of the basilar artery directly inferiorly along the fifth nerve to the internal carotid artery. There was no indication of this abnormal artery in this series of human embryos.
Figure A5> plane G, illustrates the superior progression of the internal carotid artery past the hypophysis (HYPO.PH.), immediately superior to which it joins the posterior communicating artery. The stem of the stapedial artery arises as a well marked branch of this crest of the internal carotid artery. The posterior choroidal artery lies where it did in the previous plane. Inferiorly, the anterior choroidal artery is cut as it arises from the internal carotid anterior to its junction with the posterior communicating artery, and here is arching posteriorly and superiorly to gain access to the inferior posterior and medial aspect of the temporal lobe.
Figure A6, plane H, is a cut through the temporal pole of the cerebral hemispheres illustrating both the temporal extension of the caudate nucleus as well as its thalamic stalk (labelled here C.H.) extending to the preoptic region (PO.R.). The anterior and posterior choroidal arteries lie in the cleft between the cerebral hemispheres laterally and the diencephalon medially. Inferior to the hemisphere, on the right, the anterior division of the internal carotid artery appears as a prominent branch, with a distinct striate artery entering the caudate stalk. It will be noted that this division lies superior to the optic nerve (II N)
On the left the division into medial and lateral branches has occurred, the middle cerebral artery (M.C.A.) lying in the endorhinal fissure and the anterior cerebral artery (A.C.A.) lying inferior and medial to it. The striatal branches of these arteries are not apparent but their respective areas of distribution are clearly indicated.
Figure A7, plane H ! , shows a traverse through the diencephalon and cerebral hemispheres in the poserior region of the foramen of Monro (F. of M.). The floor of the foramen as well as the ventromedial floor of the hemisphere is composed of the undifferentiated primitive caudate mass (C.N.). It is composed of a predominant medial hillock and a developing lateral hillock with just an indication of a sulcus separating the two (IT.S.). The anterior cerebral artery, with a prominant lateral striate branch, is turning medially leaving the middle cerebral artery in the endorhinal fissure. Over the roof of the diencephalon, the superior sagittal plexus is forming acorss the mid-line (S.S.P.).
Figure AS, Plane I. In this section the anterior cerebral artery has divided medially and laterally. The prominant medial hillock extends to the olfactory region and forms the lateral wall of the olfactory ventricle.
Figure A9 ? plane J. In this plane the superior sagittal plexus forms a fine network between the cerebral hemispheres. The thin walled roof of the diencephalon protrudes into the roof of the wide mouth foramen of Monro as a sharp angled ridge. The head of the caudate mass reaches its furthest anterior projection in the floor of the foramen of Monro.
Figure A10, plane K, illustrates the anterior projection of the cerebral hemisphere over the olfactory tubercles.
PLATE II (H43# original 40X).
This is a photographic reproduction of a graphic reconstruction (lateral view) of the forebrain of a 12*5 mm., C=R lengthy human embay o f as outlined in the text*
An enlarged reproduction of the area outlined as such on plate XX g showing the choroidal arteries and the posterior commnieating artery.
An enlarged reproduction of the area outlined as such on plate II $ showing the olfaeioiy ariexy stem
FIG. A3 PLANE E SLIDE 1-5-4 FIG. A4 PLANE F SLIDE F-3-3
FIG. A5 PLANE G SLIDE G-l-2 FIG. A6 PLANE H SLIDE G-5-5
FIG. A9 PLANE J SLIDE 1-1-3 FIG. A10 PLANE K SLIDE 1-4-7
Plate V is a graphic reconstruction of the nuclear configurations forming the medial wall of the mesencephalon and diencephalon of the left side of a 15*5 mm., C-K length, human embryo's brain, with the right cerebral hemisphere and the arterial and venous systems of the right side superimposed. The lettering refers to the photographic reproductions of horizontal planes listed as figures B1 to B14. Plates VI and VII are enlarged reproductions of the areas outlined on plate V. Plate A is a graphic reconstruction of a view of the anterior ventral surface of the cerebral hemispheres showing the primitive arterial network enclosing the olfactory region and the head of the caudat e-put amen mass.
The human embryo of plate V is in the same length group as the embryo depicted in plate I and, therefore, has corresponding nuclei. It shows a significant development beyond the preceding stage. In the diencephalon the dorsal thalamus has begun the rapid expansion which soon develops it far beyond the ventral thalamus. Sharing in this rapid expansion is the dorsal nucleus of the lateral geniculate body (figure B5) a growth reflected in the development of a profuse plexus of blood vessels over this region.
The cerebral hemispheres have expanded in all directions as is indicated in the more spherically shaped vesicles. Anteriorly and superiorly the hemispheres bulge well beyond the diencephalon, a deep longitudinal fissure between them (figures B5, B6, Bll and B12). Posteriorly the temporal pole covers most of the wall of the diencephalon from lateral view and the developing occipital pole is advancing over the roof.
It is during this stage of the backward growth of the cerebral hemispheres over the diencephalon that the basis of that complex structure, the velum interpositum, is formed. The basis of this structure is that area of mesoderm and vascular capsule of the brain, the pia mater, which is enclosed between the diencephalon and the expanding cerebral vesicles. Into this fissure extends a double fold of pia mater, the dorsal layer of which is closely applied to the basal surface of the hemisphere, the ventral layer foiming the pial investment of the diencephalon. The important parts of the velum are an anterior portion in relation to the roof of the foramen of Monro and the medial wall of the lateral ventricles (figures B5 and B8) and a posterior part in relation to the roof of the diencephalon (figure B6)• Anteriorly the medial wall of the hemisphere, inferior to the hippocampus, becomes thinned to an ependymal layer which becomes converted into a glandular or secreting epithelium. The mesoderm, at the lateral edges of the velum, project within the lateral ventricles at this thinned margin, the surface of which is therefore, covered ty a reflection of this membrane. At this stage these projections form the first indication of the choroid villi. When the mesoderm carried the blood vessels of the choroid plexus into the villi they become capable of secreting cerebral spinal fluid. The medial wall of each cerebral vesicle, from the foramen of Monro to the descending horn becomes similarly inflected and this line of inflection is shown as a clear stipled area in plate V (see figures B5 to B8) • The choroid villi develop to completely fill the cavities of the embayonic lateral ventricles. For the first three months of Embryonic life, these ventricles are relatively large and their containing walls thin. The velum and the choroid plexus must play an important part in the development of the cerebral vesicles in this early period of growth.
The roof plate of the diencephalon, from the foramen of Monro to the posterior commissure, becomes similarly modified. The thin roof of the third ventricle is formed ty a layer of ependymal cells invested by richly vascular pial tissue from the velum interpositum, the two together forming the tela choroidea. From the tela a double row of vascular tufts, invaginated along the median plane projects into the ventricle forming its choroid plexus. The plexus extends from the most caudal portion of the roof to the interventricular foramen where it becomes continuous with the choroid plexus of the lateral ventricles.
At the stage shown in plate V, primitive venous drainage vessels are forming in the velum, forming a primordium of the drainage system of the Galen veins and straight sinus of the tentorium cerebri.
This system will be explained below.
Major transformations have occurred in other regions of the expanding telencephalon. In the floor the basal ganglia form a large undifferentiated mass, much as in the previous stage, but now* the expanding hemispheres are beginning to mould this mass into its definitive form. Anteriorly, the extending head of the caudate-putamen mass is prominent, lateral to the olfactoiy region (figure B12). Posteriorly, the expanding temporal lobe is drawing the body of the caudate mass into an elongated extension into the inferior horn (figure B5)• The thalamic stalk (figures B7 and B8) is unchanged from the preceding stage, as is the morphology of the medial and lateral hillocks. The growth of these hillocks is emphasized ty the deepening of the intrathalamic sulcus (figure B8). There is still no indication of an internal capsule and the corpus striatum persists in its primitive form.
The definitive morphology of the circle of Willis is more clearly established at the 15*5 mm. stage* The posterior division of the internal carotid artery, namely, the posterior communicating artery and the roots of the future posterior cerebral artery, illustrated in plate VI, remains essentially unchanged. At the same time the roots of the mesencephalic and diencephalic arteries have multiplied in number and have begun to form a common stem springing from the anterior end of the basilar artery (figure B2)• The enlarged area represented in plate VI illustrates the closed loop formed between the anterior and posterior choroid arteries, as previously outlined, but with modifications in response to the changes in the expanding telencephalon* The posterior choroidal artery branches from the stem of the posterior cerebral artery and the anterior choroidal artery springs from the anterior division of the internal carotid artery, much as in the preceding stage. The distribution of these arteries now consists of an elaborate plexus overlying the lateral geniculate area (dotted vessels in plate VI), an advance which foretells the definitive morphology of these arteries* This plexus is in response to the rapid elaboration of the underlying dorsal nucleus of the lateral geniculate bocfcy (labelled D.TH* in plate VI) (figure B5) • The entire area is overlaid by the posterior expansion of the temporal pole. The posterior portion of the inflection line, labelled in plate VI choroid plexus. Is illustrated as a clear stipled area. This growing area is in close proximi-ty to the blood plexus formed by the choroidal arteries and hence the area gains its blood supply ty well marked branches from this plexus* The latter branches are seen entering the invaginated area from a posterior inferior direction and appear equal in importance with the branches to the lateral geniculate body. This condition is reported ty Abbie (1932 - 1933) to be the morphology of the blood plexuses found in the adult ape and other Primates, while that of the adult man is that the choroid branches are the main branches of the choroidal artery system and the arteries to the lateral geniculate body of less importance.
Plate VI illustrates another definitive condition being established, at this stage, with regard to the anterior choroidal artery (A.CH.A.). The caudate extension into the temporal pole lies in direct contact vrith the anterior choroidal artery as the artery arches posteriorly and superiorly from its origin to the plexus (figure B5)• The branches that arise from the anterior choroidal artery as a result of this relationship will provide blood supply to the tail of the caudate nucleus, the amygdaloid nucleus, the posterior inferior half of the internal capsule, the optic radiation and the inner segment of the lentiform nucleus. Plate VI illustrates the artery as it passes dor- sally, posteriorly, then anteriorly to gain the inferior and medial surface of the temporal pole (dotted portion) and enter the medial invagination of the velum interpositum.
The posterior communicating artery has the same morphology as in the previous stage, with well developed striatal branches to the lypo- thalamus (figure B4).
Plate VI illustrates, as well, the anterior continuation of the internal carotid artery giving origin to definitive lateral striate branches, to the underlying caudate mass, then dividing into lateral and medial branches much as in the previous stage.
Plate VII illustrates the anterior continuation of the two branches of the anterior internal carotid artery. The lateral branch, the middle cerebral artery, has now reached its definitive form. The stem of the artery still lies in the endorbinal fissure, but at its lateral angle, pyriform branches extend as main vessels to lie upon the lateral aspect of the cerebral hemisphere (figures B8, B9). The primitive anterior continuation in the anterior endorhinal fissure is not shown in this plate, but is represented in plate A. The lateral striate branches to the striate mass are depicted as in the previous stage and only branches of the middle cerebral artery are shown.
The anterior cerebral artery (A.C.A.) has undergone an elaboration illustrated in plate A. Plate VII shows a lateral view of these branches. At approximately the same level as in the previous stage, the thickened edge of the lamina terminalis, the anterior cerebral artery splits into three well defined branches. The medially lying branch constitutes the artery to the lamina terminalis, while the laterally lying vessel is one of an anterior complex forming an anastomosing series with similar branches from the middle cerebral artery (figures B9 and BIO). Between lies the main continuation of the anterior cerebral artery, the primitive olfactory artery. This artery lies almost completely medial to the olfactory tubercle and nerve, as shown ty the dotted lines. The olfactory nerve runs from a dorso-anterior position where it arises from the olfactory tubercle to run inferiorly and posteriorly to its distribution in the roof of the nares.
Near its origin, along its posterior border, anises the medial striate artery (recurrent artery of Heubner, figures BIO to B14)• This artery arises from the lateral margin of the primitive olfactory artery, at this level, and runs directly laterally to lie in a groove between the olfactory tubercle and the nerve. The artery extends laterally, to curve around the expanding pyriform lobe, then dips directly into the head of the caudate- putamen mass (dotted lines).
Plate A is the frontal view of this region at this stage. Two sets of arteries are shown on each side, the middle cerebral arteries (M.C.A.) and the anterior cerebral arteries (A.C.A.). Each set of vessels is forming a primitive net of vessels enclosing the palaeo-olfactoiy region and extending across the mid-line, in the region of the lamina terminal!s, to form a plexus with the vessels of the opposite side.
The anterior cerebral artery runs medially and immediately divides into at least three main branches. A laterally running branch anastomoses with branches from the middle cerebral artery while a medial branch forms a mid-line anterior connection with the plexus of the opposite side. The large vessel running between the medial and lateral branch represents the distal portion of the anterior cerebral artery. The latter vessel, along with the medial vessel, rebranches, forming an arterial anastomosis, the forward continuation of which provides the future artery of the corpus callosum (M.A.C.C.). This highly plexiform arterial network is the primitive morphology of the anterior communicating artery. At least two sets, and probably more, of anterior continuing vessels provide a large combination of possible abnormalities involving the adult anterior communicating artery, anterior cerebral artery as well as the origin and course of the medial striate artery. Mary of these abnormalities have been illustrated ty ¥. E. Dandy (1945) and include a plexiform anterior communicating artery and origins of one or more anterior cerebral arteries from just one side of the plexus. This condition is one factor in explaining possible abnormal origins of Heubner*s artery. Another factor involved is the lateral plexus which the anterior cerebral artery forms with the middle cerebral artery.
The middle cerebral artery (M.C.A.) as illustrated in plate A, is branching over the pyriform lobe, the lateral aspect of the cerebral hemisphere, as well as sending a series of medial branches to form an anteriorly running series of anastomoses with lateral branches of the anterior cerebral artery. The medial striate artery is the most anterior of this series of olfactory anastomoses, and illustrates again that a rapidly developing nuclear region involves for itself a large plexus of vessels. In this case the blood plexus overlies the rapidly expanding head of the caudate-putamen mass. As the pyriform lobe proceeds to fold upon itself, bending the endorhinal fissure, as explained previously, the only vessel connection left to this head is usually that shown in the diagram, the medial striate vessel. This vessel is a direct connection from the anterior cerebral artery to the head of the caudate-putamen mass. The anastomosing vessel that originates from the middle cerebral artery usually disappears, along with the rest of the anastomosing series from both vessels. Striate branches, probably remnants of this series, persist as blood vessels to the caudate head from the cerebral vessels*
The lateral series of anastomoses between the anterior and middle cerebral arteries is an important one with respect to abnormalities involving Heubner*s artery alone. The artery may arise as a continuation of any one of the channels of the original anastomosing series. As such it may arise laterally from the anterior cerebral artery or medially from the middle cerebral artery. If the artery arises from the former, it may do so in any position along the proximal portion of the anterior cerebral artery from near its origin at the internal communicating artery. If the artery arises from the middle cerebral artery it could do so from its proximal portion in any position from its origin at the internal carotid artery to the lateral angle of the endorhinal fissure where the middle cerebral artery enters the Sylvian fissure. Usually it would not originate on either vessel beyond these limits as the medial striate vessel represents the most anterior vessel of the anastomosing series. Critchley (1930) reported a study on abnormal arteries in this area, in which 80% of medial striate arteries were normal, in the sense that they arose from the proximal portion of the anterior cerebral artery, the other 20 % arising from the internal carotid artery or the middle cerebral artery.
Subsequent development of the nuclei in this region of the brain results in an infolding which alters considerably the course of the medial striate artery. However, once the simple relationship of origin and supply is established, as illustrated in plate A, it is maintained, through the infolding process, to the adult form.
Summary of Arteries for the 15.5 mm Stage
There are two principal arterial systems with which we are concerned at this stage, the choroidal system and the olfactory system. The choroidal vessels have advanced, in this one stage, from a primitive morphology consisting of a major branch to the lateral geniculate body, to a plexus formation from which the adult arteries derive their name. Major branches are beginning to appear, running to the infolding velum interpositum which in later stages become the major branches of the choroidal arteries. In response to its relationship with the posterior extension of the caudate mass, the anterior choroidal artery soon establishes a blood supply to this region which persists in adult morphology.
The olfactoiy system has developed In response to the growth of the olfactoiy nuclei as well as to the anterior extension of the head of the caudate-putamen mass. The primordial network between the anterior cerebral artery and the middle cerebral artery has resulted in the formation of the recurrent artery of Heubner, arising laterally from the anterior communicating plexus. Two conditions affect abnormalities of the recurrent artery:
(1) Abnormalities of Heubner 1 s artery in connection with abnormailties in the anterior coumiunieating and anterior cerebral arteries. These -will be discussed further in connection with plate B.
(2) Abnormalities of Heubner*s artery alone, a condition affected ty the lateral anastomosing series, in which Heubner*s artery may arise from either anterior cerebral, middle cerebral or internal carotid arteries. Combinations of thes abnormalities will be discussed in connection with plate B.
As in the last stage, the entire forebrain is drained by the primitive anterior plexus but an elaboration has occurred in the system draining the superior aspects of the hemispheres and diencephalon. The superior sagittal plexus drains both medial and lateral aspects of both cerebral hemispheres as well as receiving the posterior drainage of the straight sinus (figure B5). The development of the velum interpositum has resulted in the formation of the definitive straight sinus (S.S.) lying in the roof of the diencephalon (figure B6). The anterior portion of the straight sinus is most important at this stage and is partly represented in plate VI• the lateral edge of the velum has invaginated the medial wall of the hemisphere to form the choroid plexus villi. Anteriorly the velum invaginates the roof of the foramen and in so doing drains well marked branches of the straight sinus with it. These branches are represented as leaving the anterosuperior aspect of the choroid plexus to enter the straight sinus (figure B7).
Of major importance is the establishment of the superior venous drainage of the body of the caudate nucleus from this branching astern draining into the straight sinus. One or two major channels at the level of the mid-thalamic region, enter the junction of the cerebral hemisphere with the diencephalic wall, i.e. the future Internal capsular region,and running posteriorly and superiorly to the foramen of Monro, enter and drain the dorsal bo<$r of the caudate nucleus. These veins are illustrated in plate VI as the caudate extensions of the straight sinus (see figures B6 & B7). With further development this superior drainage will develop anastomotic channels with cortical veins but with this technique these internal channels are not evident. The vessels present at this stage represent the primordia of the internal cerebral veins. Plate VI shows an anterior continuation of the straight sinus over the roof of the foramen draining the lamina terminalis.
Figure Bl, plane C, illustrates the relationship of arterial branches with the mid-brain and hind-brain. This plane provides a basis from which the vessels can be traced to their major trunks.
Figure B2, plane B, represents a cut through the mid-brain, the habenular nucleus (H.N.) forming its roof and the tegmentum (TEG.) forming its floor. Posteriorly lies the hind-brain. Between, lies a large 11 cross” of vessels forming termination and origin of mary vessels for both sides of the Embryo. Superiorly originate the mesencephalic and diencephalic vessels. Inferiorly, the posterior communicating artery is terminating in the basilar artery. From this union the anterior choroidal artery runs anteriorly .
The anterior venous plexus is well represented laterally.
Figure B3, plane E, represents a cut through the posterior portion of the diencephalon and the inferior portion of the hind-brain. The configurations of the diencephalon divide it into a dorsal thalamus, ventral thalamus and hypothalamus. Superiorly, the posterior choroidal artery (P.CH.A.) runs lateral to the inferior border of the ventral thalamus, while inferiorly the posterior communicating artery lies lateral to the hypothalamus.
The large basilar artery (B.A.) lies posteriorly between the diencephalon and rhombencephalon.
Figure B4, plane F, illustrates a cut through the mid-section of the diencephalon including the posterior tips of the cerebral hemispheres. The dorsal thalamus is separated from the ventral thalamus by the prominent zona intrathalsmica (Z.IT.) all of which lie superior to the developing hypothalamus. The lateral geniculate area is represented on the lateral wall of the dorsal and ventral thalami, over which the plexus of choroidal vessels is forming. The posterior choroidal artery (P.CH.A.) has gained entrance to the plexus by passing anteriorly superiorly from its origin to gain the medial aspect of the temporal pole. Posteriorly, the posterior communicating artery (P.C.A.) and the anterior choroidal artery (A.CH.A.) have separated, the latter artery proceeding superiorly to lie inferior to the temporal pole and gain access to this aspect of the plexus. The basilar artery is in its familiar place. The superior sagittal plexus is draining into the anterior plexus.
Figure B5, plane F*, shows the di encephalon, much as it was in the previous plane and the telencephalon here cut through a more expanded portion. Superiorly, the hemispheres rise above the diencephalon while medially the invagination of the thinned wall, by the velum, is picked up posterior to the foramen. Inferiorly, the floor of the hemisphere is composed of the temporal extension of the striate mass. In the velum, the branches of the choroidal arteries mix, in plexus form, with the venous branches of the straight sinus. Lateral to the hypothalamus, the posterior communicating artery joins the internal carotid artery. Posteriorly, the basilar artery is giving lateral branches to the ganglion of the fifth nerve, while the vertebral artery is approaching anteriorly to join the basilar artery beneath the floor of the hind-brain. Superiorly, the superior sagittal sinus has formed a plexus between the rising crests of the hemispheres as well as forming a definite channel in the roof of the diencephalon.
Figure B6, plane G, represents a cut immediately posterior to the foramen of Monro. The velum is projecting into the lateral, ventricle as well as forming a dense plexus of vessels in the roof of the diencephalon. The hemispheres are joined ty a stalk to the diencephalon providing a continuation of the caudate nucleus inferiorly with the hypothalamus and superiorly with the dorsal thalamus. Veins drain superiorly from this stalk and from the invagination to enter the straight sinus but these are not clearly indicated in the photographs but are traceable with the microscope. These veins are the caudate extensions of the straight sinus which are the primordia of the internal cerebral veins. Inferior to the stalk the anterior internal carotid gives lateral striate branches to the caudate mass and lateral to the hypothalamus the proximal portion of the internal carotid artery (I.G.A.) appears as a prominent vessel. The basilar artery (B.A.) is cut through its inferior arch beneath the hind-brain.
Figure B7, plane G% illustrates a traverse through the posterior aspect of the foramen of Monro. In the roof the velum is invaginating as two projecting ridges which contain the veins draining the choroid plexus anteriorly into the straight sinus. The medial wall of the hemisphere is formed ty the thickened hippocampus primordium (Hippo.P.) • The floor is formed ty the large undifferentiated corpus striatal mass, vaguely separated into medial and lateral hillocks. This mass projects inferiorly to the preoptic region. Inferior to the pyriform cortex, the anterior division of the internal carotid artery is dividing into the lateral and medial branches• On the left, the inferior venous plexus draining the striate mass is intermingled with the lateral striate arteries. The hypophysial invagination caps the inferior aspect of the diencephalon.
Figure B8, plane H, is a cut through the region of trie anterior commissure, the optic region projecting as the optic nerves. The sulcus dividing the caudate mass is more prominent. The anterior cerebral artery is moving medially to lie lateral to the anterior commissure while the middle cerebral artery is branching laterally around the pyriform cortex. In the roof of the foramen the lateral projections depict the anterior aspect of the velum interpositum. Posterior to the roof of the pharynx, the internal carotid artery is cut through its proximal portion.
Figure B9, plane H 1 , illustrates the anterior aspect of the foramen of Monro and lamina terminalis. The superior aspect of the hemisphere is an excellent illustration of the inverted vertebrate brainf the thickened walls fold inwards to form a tube and the thin velum forms a roof plate connecting the inversions. The anterior extension of the caudate nucleus foms the floor and part of the lateral wall. The branches of the middle cerebral artery cover the olfactozy lobes and pyriform lobes and extend laterally over the cerebral hemispheres. The anterior cerebral artery has divided into lateral and medial branches, the latter infolded with the lamina terminalis as it loops forward to join the thin roof. The lateral branches form a plexus over the olfactory tubercle with the medial branches from the middle cerebral artery.
Figure BIO, plane I, sections the hemispheres just anterior to the lamina terminalis and immediately superior to the origin of the olfactory nerve and shows the root of the middle striate artery from the primitive olfactory artery.
Figure Bll, plane J, on the right, shows a middle striate branch running in a groove between the olfactory tubercle and nerve.
The head of the caudate mass forms a prominent mass in the lateral floor of the hemisphere.
Figure B12, plane J*, is a continuation of the above plane, showing a distinct connection between the olfactory tubercle, nerve and nares.
Figures B13 and B14 illustrate this path of the olfactory nerve. The medial striate artery has completed its course superiorly over the nerve to anastomose with medial branches from the middle cerebral artery over this region.
PLATE V (H5X f original 401)
This is a photographic reproduction of a graphic reconstruction (lateral view) of the forebrain of a 15*5 C=R lengthy human embxyo with arteries and veins superimposed*
An enlarged reproduction of the area outlined on plate V, showing the choroidal artery system^ including the posterior communicating artery, the choroid plexus and the caudate extensions of the straight sinus*
An enlarged reproduction of the area outlined on plate V, showing the olfactory system of the anterior cerebral artery and pyriform extensions of the middle cerebral artery.
PLATE A (original 4QX)
A frontal view of the anterior ventral surface of the hemispheres outlined in plate V @ It Illustrates the primitive medial and lateral plexuses eventually responsible for producing^ respectively the anterior communicating artery and the medial striate arteriesa
FIG. B1 PLANE C SLIDE C-2-3 FIG- B2 PLANE D SLIDE C-5-7
FIG. B3 PLANE E SLIDE D-3-2 FIG. B4 PLANE F SLIDE E~3~2
FIG. B5 PLANE F ? SLIDE F-l-3 FIG. B6 PLANE G SLIDE F-4-2
FIG. B7 PLANE G' SLIDE G-l-5 FIG. B8 PLANE H SLIDE G-4-5
FIG s 339 PLANE H 8 SLIDE H-2-3 FIG • BIO PLANE I SLIDE H-5-2
Plate VIII is a graphic reconstruction of the nuclear configurations forming the medial wall of the mesencephalon and diencephalon of the left side of a 20.0 mm., C-R length, human Embryo^ brain with the right cerebral hemisphere and the arterial and venous stems of the right side superimposed. The lettering, on the right, refers to photographic reproductions of horizontal planes listed as Cl to CIO. Plates IX, X and XI are enlarged reproductions of the areas outlined on plate VIII.
The expansion and elaboration of the crebral hemispheres mark the advance of the nuclei to this 20 mm. stage. Now the posterior expansion of the cerebral hemispheres includes a dorsal occipital pole as well as a ventral temporal pole (figures Cl and C2). The dorsal expansion carries the hemispheres well above and beyond the underlying diencephalon, deepening the longitudinal fissure, but yet does not hide the diencephalon from lateral view. The posterior expansion of the temporal lobe is further extending the boc^r of the caudate nuclear mass. Medially, the connection of the hemisphere with the di encephalon, the internal capsule, passes through the corpus striatum separating it into caudate and lenti- form nuclei (figure C5) • The elaboration of the internal capsule is the most significant nuclear advance marking this stage and is illustrated in plate VIII as two arrows running posteriorly and inferiorly from the corpus striatum into the di encephalon.
Posteriorly, each cerebral hemisphere is continuous with the diencephalon by way of the corpus striatum; inferiorly, continuous with the hypothalamus and posteriorly, continuous with the optic thalamus.
Hence it is the corpus striatum -which forms the bond between these two members of the forebrain. An elaboration of pallial fibers joining the cortex to lower centers must, of necessity, pass through the posterior connection of the corpus striatum to the optic thalamus. There is no other pathway. The internal capsule secondarily joins the cerebral hemispheres to the diencephalon. It divides the dorsally lying body of the caudate nucleus from the inferior globus pallidus. The internal capsule consequently passes through the mass of the putamen nucleus but leaves small bridges of connecting nuclear tissue causing a striate appearance from which the body gets its name. Anteriorly the capsule does not separate the putamen from the caudate and they form a large continuous head (labelled in plate VIII as C.N.). Inferiorly, the original stalk to the preoptic region is well defined (figure C5 to C6). Laterally, the corpus striatum occupies a large portion of the lateral wall (figures C3 to C4) and seen from a lateral view extends superiorly beyond the foramen of Monro. This is depicted, in plate VIII and subsequent reconstructions, as a black margin superior to the foramen.
The foramen of Monro still offers wide communication to the lateral ventricles from the third ventricle. In the roof of the foramen the velum has undergone elaboration (figure C2). Laterally, the invagination of the medial wall of the hemisphere has lengthened and broadened in response to the expanding hemisphere.
In the diencephalon, the dorsal thalamus extends far beyond the ventral thalamus and dominates the entire diencephalon. The lateral geniculate body has become a prominent body.
The definitive morphology of the circle of Willis is established ty the 20 mm. stage, in all important aspects. The posterior division of of the internal carotid* the posterior communicating artery and the posterior cerebral artery, now arises as a definite stem from the basilar artery from which, in turn, spring both the inferiorly running posterior communicating artery and the superiorly running posterior choroidal artery (figure B9)• The branches of the posterior cerebral artery, still defined as mesencephalic and diencephalic arteries, supply the field of the adult artery, that is, the anterior region of the mesencephalon, the hippocampal and paraterminal areas and the posterior, medial and lateral aspects of the cerebral hemispheres.
The enlarged area in plate IX represents part of the closed loop of the choroidal arteries. The temporal pole overlies a major portion of the area, as inscribed by the heavy black line. The line of inflection is represented by the clear stipled area. The posterior line of union of the hemisphere with the diencephalon, inferior to the foramen of Monro, is roughly along the posterior border of the blackened area, extending with the arrows into the diencephalon.
Both choroidal arteries gain access to their respective fields of supply by passing posteriorly and superiorly to this stalk (figure C6 and C7). The posterior choroidal artery does this by virtue of its origin from the posterior cerebral artery. Plate IX Illustrates only two main branches of the posterior cerebral artery, a lesser branch turning dor- sally to the area of the lateral geniculate body and a main branch running anteriorly to enter, from behind, the inferior aspect of the inflection area. At all times it is superior and posterior to the connecting stalk.
The anterior choroidal artery originates from the enlongatea stem of the anterior internal carotid artery. Its field of supply Is the choroid plexus. Consequently, the posterior growth of the hemispheric stalk forces the artery into a posterior arch between these two anchoring points- Superiorly the artery lies in the velum parallel to the posterior choroidal artery. A large branch establishes blood supply to the underlying tail of the caudate nucleus. This relationship of the anterior choroidal artery to the posterior region of the corpus striatum is now definitive.
The posterior communicating artery forms a bridge between the origin of the choroidal vessels running laterally to the inferior wall of the hypothalamus and almost parallel to the inferior, medial lying basilar artery.
Plate I illustrates the anterior continuation of the internal carotid artery dividing into the middle cerebral and anterior cerebral arteries. The middle cerebral artery, having already achieved its definitive morphology, merely elaborates its pyriform branches over the lateral surface of the hemisphere. The striate branches are not shown.
A medial branch to the region of the middle striate artery suggests the primitive olfactory anastomosis although this series is being replaced ty the prominent medial striate artery and a network of fine vessels.
The anterior cerebral artery has undergone its final elaboration from a primitive plexiform state, as described in the 15*5 mm. stage, to the definitive state in the 20 mm. stage. This represents the last of the three major arterial systems under consideration to form the definitive state from a more primitive one. As the artery swings medially around the lamina terminalis, to lie inferior to the olfactory tubercle (O.T.), it divides into three major branches (figure C6). These branches have replaced the plexus depicted in this area in the previous stage. A frontal view of this area is reproduced in plate B. A large
branch swings posteriorly to gain the inferior anterior surface of the lamina terminalis. The second veil marked branch swings medially to join its fellow (not marked) from the opposite side. The main continuation of the anterior cerebral artery passes superiorly, to lie medial to the olfactory tubercle, where it gives origin to the large medial striate artery (figure C5)• This artery swings laterally to lie in the groove between the large olfactory nerve, anteriorly, and the developing olfactory tubercle, inferiorly. It continues to curve laterally, finally to plunge into the head of the caudat e-put amen mass. This relationship is the definitive one, with changes essentially in course due to growth and infolding, and is unchanged from the previous stage.
The anterior cerebral artery is no longer called the primitive olfactory artery. It continues anteriorly, as in the adult, swings superiorly to the anterior termination of the lamina terminalis, then proceeds dorsally and posteriorly to divide into numerous branches supplying the medial and anterior aspects of the cerebral hemispheres.
Summary of Arteries for the 20 mm Stage
With the development of the internal capsule, which unites the cerebral hemisphere to the underlying diencephalon through the caudate mass, the choroidal artery system achieves its definitive morphology.
Both choroidal arteries gain a superior relation to the hemispheric stalk by virtue of their origin and the inferior posterior course of the internal capsule. In response to the temporal growth of the hemisphere, in this region, main branches of the anterior choroidal arteries are established to the body and tail of the caudate nucleus, amygdaloid nucleus, medial and intermediate segments of the globus pallidus, posterior, inferior aspects of the internal capsule as well as to the optic tract, lateral geniculate body and choroid invagination.
The olfactozy system of arteries has undergone involution passing from the primitive plexus of vessels grouped around the olfactoiy region to the definitive branches and connections of the anterior cerebral artery. The lateral series of anastomoses, between the middle cerebral and anterior cerebral arteries, is largely replaced by a network of fine vessels and one or two major branches to the head of the c audat e-put amen mass. The medial plexus, forming an anastomosis across the midline with arteries from the opposite side, has been replaced ty a single communication, the anterior communicating artery.
The continuation of the anterior cerebral artery branches over the medial and anterior aspects of the cerebral hemispheres.
The 20 mm. stage marks the development of the internal cerebral veins (i.C.V.) which are illustrated in plate X. The velum is continuous over the roof of the diencephalon and laterally, it invaginates the medial walls of the hemispheres (clear stipled area in plate X)• Due to the rapid expansion of the cerebral hemispheres this area of inflection, at this stage, is confined almost entirely to the roof of foramen of Monro and the medial wall of the hemisphere superior to it (figures C2 and 03) . The anterior portion of the velum becomes particularly modified (figure 02) . In the previous stage, large vessels had been elaborated in this region to drain the choroid plexus. In plate XI these branches are labelled the choroid branches of the straight sinus. Interiorly, the caudate branches of the straight sinus lypass the line of inflection, enter the hemispheric stalk and pass posteriorly into the bo<%r of the caudate nucleus. Due to the expansion of the forebrain, these vessels become removed from direct connection with the straight sinus in the roof of the diencephalon with the exception of their anterior connection with the sinus in the i*oof of the foramen of Monro. In the previous stage these vessels formed a plexus which drained the hemispheres indeterminately, In the present stage these vessels join to drain each vesicle separately. They drain anteriorly to unite above the foramen as single large veins, the internal cerebral veins (I.C.V,), The two internal cerebral veins change direction by draining posteriorly in one large vein, the primordium of the vein of Galen, which in turn drains into the straight sinus.
The superior sagittal sinus, posteriorly joining the straight sinus, is still plexiform in the midline. Both sinuses drain posteriorly into the anterior plexus. The adult morphology of the Galen drainage system is established by the 20 mm, stage. Elaboration of this basic morphology will occur in response to the elaboration of the telencephalon,
Figure Cl, plane C, illustrates the expansion of the cerebral hemispheres which come to overshadow the underlying diencephalon. The cut has transversed the anterior portion of the roof of the diencephalon. Superiorly, the velum has developed a dense plexus of veins v&iich drains both into the central channel in the roof of the diencephalon as well as into the plexiform superior sagittal sinus. Immediately inferior to the roof of the diencephalon the large vessel of the straight sinus is apparent. It is the continuation of this vessel -which drains the anterior portion of the velum (illustrated in the next section). Anteriorly, between the hemispheres, are small branches of the anterior cerebral artery.
Figure C2, plane D, represents a cut through the anterior portion of the velum. It passes through the area immediately superior to the anterior roof of the foramen of Monro and illustrates the anterior attachment of the cerebral hemispheres to the diencephalon.
The velum is making an extensive invagination into the roof of the foramen* The vessels draining the posterior lying infected area have approached anteriorly to form a large vessel on each side (I.C.V.).
These vessels drain into the main vessel of the straight sinus designated in the previous plane. Inferiorly the branches of the anterior cerebral artery lie between the anterior lobes of the hemispheres. Laterally, the wall of the hemisphere is occupied Ty the prominent head of the caudate mass and this plane represents the anterior extension of this mass. Superiorly the walls of the diencephalon are composed of the dorsal and ventral thalami.
Figure C3> plane E, traverses midway through the open foramen of Monro. The dorsal thalamus constitutes the major portion of the walls of the diencephalon. Inferiorly, this region is continuous with the medial wall of the hemisphere, providing a groove in which lies the caudate branch of the straight sinus. Immediately superior to this groove, the wall of the hemisphere is veiy thin and the line of inflection now appears superior to the margin forming the roof of the foramen. Medial to this thin portion of wall lie the choroid branches of the straight sinus. The anterior anastomoses of the choroidal vessels meet in this same region. Inferiorly, the large medial hillock of the corpus striatum forms the lateral wall of the ventricle of the olfactoiy tubercle.
Figure C4> plane F, cuts the telencephalon immediately inferior to the foramen of Monro and illustrates the posterior hemispheric stalk. Entering this stalk, the caudate branch of the straight sinus gains superior access to the caudate body. The caudate bo(^ is divided into definite medial and lateral hillocks. Inferiorly, the ventricle of the olfactoiy tubercle is open and posteriorly continuous with the third ventricle. Between the folds of the olfactoiy tubercle, the main branches of the anterior cerebral artery show as two prominent vessels. Laterally, the middle cerebral artery branches over the pyriform cortex.
Figure C5* plane F*, traverses the mid-section of the diencephalon, The internal capsule (I.C.) appears as a clear stria traversing the caudate mass as it passes through the posterior stalk. Medial to the hemisphere, branches of the choroidal arteries mingle with extensions of veins draining into the internal cerebral vein. Inferiorly, the olfactory tubercle has given way to the olfactory nerve and the medial striate branch runs laterally in its groove to seek its destination in the head of the caudate nucleus.
Figure C6, plane G, is a cut through the floor of the midbrain, the hypothalamus, the separated temporal lobes and the superior aspect of the optic cups. The anterior cerebral vessels are still medial but are preparing to ease laterally to join the middle cerebral artery at their common origin. Medial to the temporal lobe, the posterior choroidal artery enters the cleft, superiorly, while the anterior choroidal artery enters inferiorly. The arteries lie superior to the hemispheric stalk. The posterior extension of the caudate mass forms the thickened floor of the temporal lobe.
Figure C7, plane H, shows the collicular plate forming the roof of the mesencephalon and a thickened floor separating it from the hypothalamus. The temporal poles are the same as in the last section. On the right side, the anterior choroidal artery arises from, the anterior continuation of the internal carotid artery and runs superiorly to the temporal pole. The posterior choroidal artery lies lateral to the floor of the diencephalon.
Figure C8, plane I, shows the mesencephalon separated from the wall of the hypothalamus. In the intervening space, the posterior
PLATE VIII (H17, original 40X) •
This is a photographic reproduction of a graphic reconstruction of a lateral view of the forebrain of a 20 mm CR length human embryo with the more important arteries and veins superimposed See text.
An enlarged reproduction of the area outlined on plate VX1X showing the distribution of the choroidal arteries at this stage. See text.
An enlarged reproduction of the area outlined on plate VIII showing the distribution of the anterior and middle cerebral arteries around tiie ©Ifactoijr region*
An enlarged reproduction of the area outlined on plate VIII shoeing the formation of the superior drainage of the internal cerebral hemispheres^ the internal cerebral veins®
FIG* Cl PLANE C SLIDE 5-2-5 FIG, 02 PLANE D SLIDE 7-1-4
FIG. 03 PLANE E SLIDE 8-1-6 FIG. 04 PLANE F SLIDE 10-2-1
FIG. 05 PLANE F* SLIDE 12-1-5 FIG. C6 PLANE G SLIDE 13-2-5
FIG. C7 PLANE H SLIDE 14-2-4 FIG* C8 PLANE I SLIDE 17-1-2
Plate XII is a graphic reconstruction of the 25.C mm. stage,
C-R length, of the brain of a human embryo. It illustrates the nuclear configurations of the medial wall of the right half of the mesencephalon and diencephalon with the left cerebral hemisphere and the blood vessels of the left half of the brain superimposed for three dimensional effect. The lettering on the left refers to planes photographically reproduced as figures D1 to DIB, while the numbering on the right refers to the slide, row and section number of the original embryo. Plates XIII, XI? and XV are the enlarged reproductions of the areas outlined on plate XII• Plate B, a frontal view of the same region as in plate A, shows the transformation of the vessels over the olfactory region into their adult morphology.
The major nuclear change, to this stage, has been one of extension and growth. The dorsal thalamus constitutes the greater mass of the diencephalon. In the telencephalon, the cerebral hemispheres have maintained their accelerated expansion over other regions of the forebrain. Posteriorly, the temporal and occipital poles are beginning to encroach upon the anterior aspects of the mesencephalon (figure D2). Interiorly, the temporal pole Is beginning to cover the hypothalamus from lateral view (figure D6)• Superiorly, the longitudinal fissure extends deeply between the hemispheres which rise well above the under- lying diencephalon. Anteriorly, the frontal lobes bulge well beyond the underlying plfactoiy region.
The corpus striatum is approaching its adult morphology. Anteriorly, the continuous head of the caudate and putamen nuclei (plate XII, H.C.N. and P.) forms a large mass Hying lateral to the olfactory stalk (figure D15) • Posteriorly, this head is continuous with the separated boc^r of the caudate and lentiform nuclei (C.N., P.). The internal capsule, illustrated in plate XII as medially directed arrows and labelled I.C., is a well developed mass of tracts clearly separating the body of the caudate nuclear mass from the putamen and globus pallidus (figures D9 and DIO). Posteriorly, the tail of the caudate nucleus is continuous with the amygdaloid mass in the floor of the temporal pole (figure D7).
In the roof of the diencephalon, the velum interpositum is approaching its definitive morphology in that the single straight sinus drains the double internal cerebral veins and in turn drains a large superior sagittal vessel. The lateral invaginatlng edges of the velum extend along the medial wall well posterior to the narrowing foramen of Monro (figures D7 and D8)• The line of inflection arches posteriorly into the temporal pole.
The morphology of the circle of Willis which was established in the 20 mm. stage is essentially unchanged in the 25 mm. stage. The enlarged area shown in plate XIV illustrates the slow formation of a definite stem for the adult posterior cerebral artery. Posteriorly, the superior cerebellar artery (S.C.A.) is arising from the basilar as a single stemmed vessel (figure D3, D4)® This stage is critical for these vessels, in terms of adult morphology, in that this region constitutes the source of the largest number of abnormalities in the adult circle of Willis.
The key to the situation lies in the origin of the posterior cerebral artery. In primitive forms it originates as a posterior branch of the cranial division of the internal carotid artery. In response to the posterior elaboration of the forebrain, the posterior cerebral roots gain their source of blood from progressively posterior diencephalic branches of the basilar artery. In the primitive mammalian forms it arises as a definite stem of the basilar artery. The posterior communicating artery persists as the posterior tract of this journey providing a link for the artery to its original source, the internal carotid artery. When the anterior communicating artery is completed, these vessels form an interconnecting circle of blood vessels wherety blood may be shunted from the carotid system to the vertebral system, or vice versa, as the need arises. Physiologically, the posterior communicating artery functions as a "safety valve" mechanism equalizing blood pressure between the two arterial systems.
If the posterior division remains in its "primitive" form the main source of blood to the posterior cerebral artery remains the internal carotid artery, via the posterior communicating artery. The latter artery remains large and the stem of the posterior cerebral artery to the basilar is correspondingly small. If the posterior division persists in a "transitory" state, the posterior cerebral artery derives its blood supply equally from the basilar and the internal carotid arteries. The posterior communicating artery persists in an enlarged state that is of equal Importance to the basilar stem. If the posterior division proceeds to the adult stage, then the posterior communicating artery dwindles in size ^while the basilar stem enlarges as the main source of blood supply. The size of the posterior communicating artery is, in the adult, approximately one-half that of the posterior cerebral artery which in turn is approximately one-half the size of the basilar artery. There is less relative difference in size of the component vessels at birth or in the Embryo. The posterior communicating may continue to undergo involution, probably in response to a lack of use, until it may be represented ty a thread of tissue or be entirely absent. Combinations of primitive, transitional and normal forms of the posterior communicating artery give a potential larger blood supply originating from the internal carotid artery.
Other possible abnormalities of the posterior division are illustrated in plate XIV. At least two centrally displaced vessels, normally impinging upon the hypothalamus, are enlarged superiorly to join the blood supply of the dorsal thalamus and the choroid area of the telencephalon. If this blood source enlarges still further, either choroidal artery, or both, may undergo involution or disappear completely, the adult choroidal vessels appearing to originate from the posterior communicating artery. If the anterior or posterior choroidal arteries did not involute, there would simply appear an accessory number of choroidal vessels.
The anterior and posterior choroidal arteries, plats XIV, present the same picture as in the previous stage. Both gain entrance to the invaginated area by passing medial to the temporal pole (dotted vessels). The anterior choroidal artery expands its field of supply in response to this position, but is essentially that of the previous stage and corresponds to the adult field of supply in the adult (figure D7).
The superior aspect of both anterior and posterior limbs of the internal capsule receives its blood supply from underlying striate branches of the cerebral arteries. The region depicted in plate XIV is subject to a large number of possible variations in blood supply. The striate arteries may take over the area of supply of the choroidal vessels and vice versa. Normally, the area of supply of the striate branches of the middle cerebral and anterior cerebral arteries would remain quite distinct but one series may well overlap or overtake the supply of the other. Rubenstein (1944) reports a situation in which the recurrent artery of Heubner was blocked resulting in rigidity (involvement of the head of the caudate) and facial paralysis (involvement of the internal capsule through the head of the caudate-putamen mass), The facial paralysis gradually passed off as the blood supply to the internal capsule was restored, but the rigidity persisted. This indicates a multiple source of blood possible for this region of the capsule; i.e. lateral striate branches from the anterior cerebral artery, from the middle cerebral artery and directly from the internal carotid and posterior communicating arteries. This gives the genu of the capsule and the body of the caudate lying above it the richest blood supply of any region in the brain. The globus pallidus, lying lateral to this region, is an area of least blood supply.
If the anterior choroidal artery is looked upon as a specialised striate branch then various adult abnormalities become clear. In about 1% of cases (as reported ty the Wistar Institute of Anatomy and Biology (1954 ) 9 the anterior choroidal artery springs from the internal carotid artery, as depicted in plate XEV. It arises from the middle cerebral artery as a specialized striate branch in about 13 %. In U% of cases .it arises from the junction of the anterior and middle cerebral arteries and from the posterior communicating artery in 8$ of cases reported. It was absent as an enlarged branch in only 2$ of cases. Anastomosis between the anterior and posterior choroidal arteries occurs either on the surface of the lateral geniculate boc£/ or in the pia of the choroid plexus, or at both sites, in 20 of 21 brains studied in the above series
Plate XIII illustrates the anterior continuation of the internal carotid and its division into ancient lateral and medial branches, the network between being the primitive network over the palaeo-olfactoxy region in Vertebrates from Fishes to man (figures D15* D16). The fact that this series of anastomoses is still present in the 25 mm, stage suggests that this region retains its primitive morphology longer than any other set of vessels in the forebrain. In the adult this primitive network is represented ty fine anastomosing vessels lying in the anterior endorhinal fissure between the anterior cerebral artery and the middle cerebral artery. In plate XIII, the anterior cerebral artery moves medially to lie lateral to the anterior commissure (A.Co.) then further medially to the inferior surface of the lamina terminalis. Heieit gives origin to two major branches; one runs medially and posteriorly to the lamina terminalis and the other runs medially across the midline, the anterior communicating artery.
The main vessel proceeds superiorly around the lamina terminalis and at the level of origin of the olfactory nerve gives origin to the medial striate artery. Its field of supply, the caudate head, is outlined in black in plate XII. This pattern is unchanged from the 15 mm. stage and indicates that in the embryo the artery pursues a relatively shorter course than in the adult.
As indicated previously, abnormalities of the medial striate artery may occur alone or in combination with abnormalities of the anterior cerebral and communicating arteries. Charles F. D.eGrais reported over 51 variations of the medial striate artery, mostly associated with an anomalous anterior cerebral artery. Plate XIII indicates that doubling of the medial striate artery is a common condition in the 25 mm. Embryo. It persists as an abnormality in 65 % of the cases in DeGrais* series. This condition was almost always accompanied by an absence of the proximal anterior cerebral artery, the medial striate vessels receiving their blood supply(from)either an anterior communicating vessel or from the middle cerebral artery. Also a common condition accompanying doubling of the medial striate artery is retention of the plexiform anterior communieating astern as it is seen in Plate A, The doubling of the striate vessels may be unilateral or bilateral. In one specimen of an anterior cerebral artery arising from a plexiform anterior communicating artery the medial striate vessel is triple on the right and single on the left. In approximately 1% of the cases the medial striate vessel arises from the anterior communicating artery as a short t medially and caudally ? directed common trunk. In about the medial striate vessel was replaced ly a dense spray of slender vessels that entered the anterior perforated space separately. Variations of this latter condition included, on both sides, short sprays assembling into a normal sized striate vessel and a normal vessel arising by two or three roots, Plate XIII depicts an area similar to that shown in plate XIV, an area of shifting Embryonic vessels in response to the needs of variously developing nuclei,
Plate B is a graphic reconstruction of a frontal view of the same region in plate A, the primitive olfactory region comprising the anterior, ventral surface of the cerebral hemispheres. It illustrates the development of adult morphology, from the 15 mm, stage to the 25 mm, stage, of the anterior communicating artery and the anterior cerebral artery. This plate bears out what is seen in plate XIII, that the lateral series of anastomoses with the middle cerebral artery is the most primitive and the most durable plexus in the forebrain. It illustrates why a duplication of the medial striate artery is the most common abnormality of this artery. The middle cerebral artery is unchanged from the 15*5 nan* stage while the anterior cerebral artery has achieved its definitive morphology.
Lying superior to the olfactory nerve the proximal portion of the anterior cerebral artery traverses medially across the underlying anterior commissure (figure D12) to the lamina terminalis. At the base of the cerebral hemisphere the artery gives off the short medial branch combining the artery with its similar member of the opposite side. This single vessel, the anterior communicating artery, in turn produces a medially directed vessel that supplies the ventral portion of the lamina terminalis and provides the stem for the adult medial artery to the corpus callosum (M.A.C.C.) . Apicaily from the origin of the anterior communicating artery, the distal portion of the anterior cerebral artery gives origin, laterally, to the medial striate artery, then arches superiorly and posteriorly along the superior margin of the medial wall of the hemisphere, much as it does in the adult.
Dandy, (1945) reports that the most common abnormality of the anterior communicating artery is that of duplication due to a persistence of some form of the primitive plexus. He indicated that the duplication may consist of two or more separate vessels, one main channel with a side branch to the anterior cerebral artery, or a definite plexiform of smaller vessels providing the connection between the two vessels. The anterior communicating artery may be absent and the two anterior cerebral arteries then join in short or long direct communication at this point.
If, in this latter condition the proximal portion of one anterior cerebral vessel is small or absent it will appear that two or more distal anterior cerebral arteries are springing from a single proximal source. As well, a single anterior communicating vessel may be classed as either large or small based on the adult normal ratio of sizes that finds this artery one-half to two-thirds the size of the proximal portion of the anterior cerebral artery which in turn is one-haJ_f the size of the internal carotid artery. Under"large" would be classed duplication of the vessel, a fused channel or one approaching the size of the anterior cerebral vessel. Under the classification , 'small' would be a slender vessel less than one-half the size of the anterior cerebral vessel. In the embryo and newborn there is less relative difference in size of component vessels than in the adult.
Critchley (1930) reports that this region of the anterior cerebral artery becomes more complex with mammalian ascent. In Fishes, Amphibia, Reptilia and Aves, no anterior communicating artery exists and the two anterior cerebral arteries are a pair of small vessels lying parallel on the mesial aspect of the olfactory lobe. The typical mammalian pattern consists of two short anterior cerebral arteries which converge and unite to form a median azygos vessel which may or may not bifurcate. The latter condition, with an apical bifurcation is the condition found in the horse. In mammals with a corpus callosum the azygos artery divides after a variable distance. In the stag and ox the anterior communication consists of a network of slender vessels, while in the human, and dog and fox at times, the pair of anterior cerebral vessels are joined in an H form by a single medial vessel. When the anterior communicating plexus is referred to as ”primitive” it then refers to a Sub-Primate form rather than premammalian form.
Godinov (1929) reports that it is extremely rare in human adult brains to have separate anterior cerebral arteries with no form of connection. If there is no anterior communieating vessels, the anterior cerebral arteries usually fuse on their medial sides. Among others, Godinov listed the following abnormalities:
- Anterior communicating artery single - 47?.
- Anterior communicating artery double - 16?.
- Anterior communicating artery V shaped - 13?.
- Anterior communicating artery N shaped -4?.
- Anterior cerebral arteries grown together - 17?.
- Anterior cerebral arteries both from the right carotid artery - 2?.
- Anterior cerebral arteries both from the left carotid artery - 7?.
He states that the two most important variations of the carotid system are:
- The ramification of both anterior cerebral arteries from the right or left carotid artery.
- Ramification of one or both posterior cerebral arteries from the internal carotid artery.
Most of the recorded variations and anomalies of these arteries are explained Ty the persistence of definite but transitoiy branches and anastomoses found in the embryo. This suggests that an incomplete involution of these temporary arteries, or of arteries normally found in the adult form, may be related to the formation of abnormalities. A normal circle of ¥illis occurs in barely 50? of reported cases (Dsndy 1945) and variation is more frequent in the posterior part of the circle. In cases with aneurysms, variation is almost twice as frequent as in cases without aneurysms; there is a higher incidence of absent arteries, but there is an even greater incidence of a closed circle with communications larger than normal.
SWMm OF ARTERIES AND NUCLEI:
Nuclei in the forebrain have undergone both elaboration and growth from the previous stage. The corpus striatum has reached its adult morphology as a result of the internal capsule becoming a well developed mass of tracts. Anteriorly, the heads of the caudate nucleus and putamen nucleus form a continuous mass -which is posteriorly imperfectly separated Ty the internal capsule into the body of the caudate nucleus and the lentiform nucleus. The tail of the caudate, inferiorly, is continuous with the arrygdaioid mass in the temporal pole.
Aberrant anterior choroidal arteries show in these reproductions with origins along the posterior communicating artery. The termination of the choroidal arteries is little changed.
Plate B represents the development of the adult anterior communicating artery formed from the primitive plexus of the 15 mm® stage. Also in adult form are the superiorly running anterior cerebral arteries and their lateral branches, the medial striate arteries.
In previous stages, venous drainage has been established from the superior aspect of the choroid plexus and body of the caudate mass.
The elaboration of these veins into separate vessels, the internal cerebral veins, has produced the main superior system of drainage of each vesicle. In the 25 mm. stage, plate XII, venous drainage has been extended to all regions of the anterior choroidal vessels and striate vessels, that is, the optic tract, lateral geniculate body $ choroid plexus, body of the caudate nucleus and the internal capsule. Plate XV is an enlarged reproduction of this area. A large vessel has been elaborated that lies directly between the thalamus and the body of the caudate nucleus, which drains forward to enter the internal cerebral vessel, which in turn drains posteriorly into a single large vessel that, after receiving other vessels, drains into the straight sinus. Previously the vessel running to the superior aspect of the caudate nucleus has been called the caudate extension of the straight sinus. Seen in this context, the adult terminology of these veins may now be used. The channel draining the dorsal aspect of the caudate nucleus, lying between it and the thalamus, becomes the posterior terminal vein, draining anteriorly into the internal cerebral vein, which turns posteriorly to form, along with other vessels, one large vessel, the vein of Galen. The adult longitudinal caudate vein is not yet in evidence. Inferiorly the middle cerebral vein, draining the striate area, has now reached its adult form, draining into the cavernous sinus. When anastomotic channels are established between the longitudinal caudate vein and cortical drainage channels, the adult venous astern will be complete.
Plate XII illustrates the posterior drainage of the straight sinus which forms a continuous channel along the midline of the roof of the diencephalon until it reaches the superior aspect of the occipital pole where it drains into the superior sagittal plexus. The latter vessel, still plexlform in areas, forms a continuous channel stretching the extent of the superior aspect of the longitudinal fissure. It drains both medial and lateral sides of the cerebral hemispheres. Inferiorly and posteriorly both superior sagittal plexus and straight sinus drain into the anterior plexus.
Figure Dl, plane G is a cut through the thickened floor of the mesencephalon where it is continuous, posteriorly, with the met encephalon. It traverses immediately behind the cerebral hemispheres. In the roof there is a pmal1 plexus of veins draining anteriorly along the roof of the mesencephalon into the straight sinus. Lateral to the floor of the mesencephalon lie the branches of the posterior cerebral and superior cerebellar vessels.
Figure D2, plane H, traverses the posterior tip of the occipital pole. Laterally the well formed anterior plexus (A.P.) is running interiorly. Inferior to the mesencephalon, filling the space between it and the hind-brain, the branches of the mesencephalic and diencephalic vessels gather to form the main stem of the posterior cerebral artexy at its junction with the basilar artery.
Figure D3, plane H 9 , is a cut through the stem of the posterior cerebral artery. Immediately anterior to the hind-brain, the basilar artery is distinguished as a large separate vessel with a large branch to the superior cerebellar artery. Figure D4, plane I, is immediately anterior to the previous figure. The cerebral vesicle on the right is extending to the temporal pole. The arteries in the mesencephalic fold illustrates the highly plexiform nature of the vessels in this area.
The basilar artery (B.A.) is a,separate vessel, and the stem of the posterior cerebral has given way to the large posterior communicating artery (P.CO.A.). Superiorly the straight sinus is a definite vessel in the mid-line of the roof of the diencephalon. The superior sagittal plexus consists of large vessels draining the lateral sides of the hemispheres. It is in this posterior region that the straight sinus drains into the sagittal plexus. The simple relation of these vessels at present will be altered to their adult morphology ty the development of such structures as the corpus callosum, tentorium cerebelii and falx cerebri.
Figure D5 plane J, illustrates the region of the diencephalon in which the lateral, geniculate body is being formed. The posterior
choroidal artery is advancing anteriorly and superiorly around the thalamus, medial to the cerebral hemisphere to gain a position lateral to the geniculate bocfr, to which it gives a major branch. The posterior communicating artery is a prominent vessel lateral to the hypothalamus. Figure D6, plane K, is essentially the same, with just the tip of the hind-brain showing and the vertebral arteries, posteriorly, and the basilar artery, anteriorly, approaching each other. In the roof, the straight sinus and superior sagittal plexus form definitely observable vessels. The expanded nature of the cerebral vesicles posteriorly covering the diencephalon is clearly shown.
Figure D7, plane L, illustrates a cut through the mid-section of the diencephalon and telencephalon depicting important relationships between the two. Two posterior structures are of importance in the cerebral hemispheres. On the medial wall, this plane illustrates the posterior nature, beyond the foramen, of the line of inflection into the temporal pole. This area of medial wall is very thin and is directly lateral to the region of the geniculate body, over which the choroidal vessels are forming a plexus. Inferiorly, the temporal extension of the caudate nucleus, with the amygdaloid mass, form a thickened, rounded ventro-medial floor.
Inferiorly, the proximal portion of the basilar artery joins the distal part beneath the hind brain.
Figure D8, plane M, illustrates the posterior hemispheric stalk, formed between the caudate mass and the thalamus. Superior to the stalk, the choroidal arteries and veins of the internal cerebral system form an anastomosing plexus. The anterior choroidal artery, to reach this plexus, arches superiorly and posteriorly to the stalk. Figure D8 illustrates the inferior portion of this arch lying in the crevice formed ty the medial wall of the caudate mass and illustrates how this portion of the caudate nucleus derives its blood supply from this vessel. The posterior communicating artexy is moving inferiorly to join the internal carotid artexy. Anteriorly is the origin of the anterior choroidal artexy from the internal carotid artexy.
Figures D9> DIO, planes N and M, are cuts through the fore- brain in an area where the large body of the internal capsule (I.C.) is entering the diencephalon. Inferior to the capsule lies the lentifona nucleus while superior to it lies the caudate nucleus. The surface of this region is the pyriform cortex. (Figure D1Q-C.N., D.C., P., G.P. and pyriform lobe).
Superiorly in the medial wall is the thin invaginated choroid plexus while above this is the thickened primordium hippocampus. The internal carotid artexy makes an arch from its source to the anterior division lying against the ventral surface of fee forebrain. Figure D9 shows a section through this arch. The proximal portion of the internal carotid artery stretches over the dorsum of the pharynx, past the hypophysis to join the posterior communicating artexy (not shorn). The anterior division of the internal carotid lies in the groove separating the telencephalon from fee diencephalon. The anterior choroidal artexy has already arisen.
In DIO, a plane just inferior to the arch of the internal carotid artery, the adult ophthalmic artery is seen arising from this arch. In this plane, the anterior carotid artexy appears as a single large branch on the ventral surface of the forebrain. Superiorly, these figures show the thin wedge shaped velum forming the roof of the diencephalon.
Figures Dll, and D12, planes 0 and 0 1 , show a great reduction in the size of the foramen of Monro. The sections illustrate the anterior portion of fee dorsal thalamus, giving way in Figure D12, to fee thin velum in the roof and thickened lamina terminalis in the floor* This thickened floor gives rise to the optic nerves, and is composed of the optic chiasma and the anterior commissure* The caudate mass joins the hemispheres anteriorly vith the olfactoiy units* On the ventral surface the anterior division gives way to the middle and anterior cerebral vessels* In figure D12 the middle cerebral artery moves laterally -while the anterior cerebral artery approaches medially to the lateral wall of the anterior commissure*
Figure D13, plane P, is representative of a plane anterior to the lamina terminalis. The choroid plexus fills a great portion of the ventricle space. The floor of the hemisphere, laterally, is composed of the large undifferentiated bulk of the head of the caudate and putamen mass, separated by a ventricular groove, from the large medial mass forming the olfactoiy tubercle. The middle cerebral artery has branches scattered over both the olfactoiy region and laterally over the sides of the hemisphere* The anterior cerebral vessels are ventrally placed beneath the hemispheres* They appear as two major branches joined across the mid-line ty a short medial stalk, which in turn is producing a posteriorly running artery, the vessel to the underlying lamina terminalis.
Figure D14> plane E, illustrates the cerebral hemispheres as in the previous plane, but shows more clearly the branches of the middle cerebral, branching over the pyriform lobe and olfactoiy region of the hemispheres (on the left)* The anterior cerebral artery is a large vessel on this side. On the right side it has proceeded superiorly to branch on the medial wall of the hemisphere. This plane is immediately superior to the origin of the olfactoiy nerve and the medial striate artery*
Figures D15 and Dl6 illustrate the cerebral hemispheres as previously shown* The middle cerebral artery branches widely over the lateral aspect of the hemisphere while the anterior cerebral artery is similarly displaced over the medial aspect* The olfactory nerve intervenes between them. In figure D15, the hemisphere on the left is cut immediately superior to the origin of the olfactory nerve and hence shows the medial striate artery in its familiar groove.
The last two figures in this series, D17 and D18, planes S and T, demonstrate the frontal bulge of the hemispheres anteriorly over the olfactory region. On the left in Figure D17, the slight bulge in the ventro-lateral floor of the hemisphere shows the most anterior portion of the head of the caudate mass. The vessels are arranged similarly to the previous plane.
(H39 f original 40X)
This is a photographic reproduction of a graphic reconstruction (lateral view) of the forebrain of a 25*0 C-R lengthy human embryo with the more important arteries and veins superimposed*
An enlarged reproduction of the area outlined as such on plate XII showing liie distribution of the anterior and middle cerebral arteries at this stage, around the olfactory region.
An enlargement of the area outlined as such on plate XII showing the choroidal arteries^ posterior cerebral artery^ posterior communicating artery and the anterior internal carotid diwision^ as thqy appear at the 25-mm® stage•
An enlargement of the area outlined as such on plate XII showing "Hie development of the internal cerebral veins at the 25 mm® stage^ and the medial wall invagination^ the future lateral choroid plexus®
PLATE B (original 40X).
A frontal view of the same region as represented in plate A p as it appears at the 25 mm® stage® The definitive anterior communi- eating artery and definitive medial striate arteries have developed from their primitive plexuses®
FIG. D1 PLANE G SLIDE 20-1-1 FIG. D2 PLANE H SLIDE 19-1-4
FIG. D3 PLANE H 1 SLIDE 18-2-3 FIG. D4 PLANE I SLIDE 18-1-3
FIG D5 PLANE J SLIDE 16-3-3 FIG• D6 PLANE K SLIDE 15-2-4
FIG. D9 PLANE N SLIDE 11-2-2 FIG. DIO PLANE N ! SLIDE 10-3-2
FIG. D13 PLANE P SLIDE 7-3-2 FIG. DI4 PLANE R SLIDE 6-1-1
FIG. D15 PLANE R ! SLIDE 5-3-4 FIG. D16 PLAI'JE R" SLIDE 5-2-2
PLANE S SLIDE 4-3-2 FIG. D1S PLANE T SLIDE 3-2-2
Plate XVI is a graphic reconstruction of the forebrain and mid-brain of a 33.0 mm, C-R length, human embryo's brain. The reconstruction illustrates the medial wall of the right half of the brain tube with the left cerebral hemisphere and the arterial vessels of the left side superimposed for space effect. Lettering and numbers as in previous plates. Plates XVII and XVIII are the enlarged reproductions of the areas outlined on plate XVI.
There has been little change in relationship between the nuclei or in the relationship of the telencephalon and diencephalon, but each part has been enormously expanded over the 25 mm. stage. This size relationship has nearly doubled, and In order to get the same proportion as previous embryos, in the camera lucida, an enlargement of 20 times was used instead of the usual 40 times. This size proportion was used throughout the reproduction. The corpus striate mass is morphologically the same as in the previous stage with the internal capsule (I.C.) forming an outstanding band of fibers through the corpus striatum (illustrated as posterior-inferior-medially directed arrows in plate XVI).
The morphology of the circle of Willis is essentially unchanged again in the 33 12 m* stage. The posterior division has shown elaboration over the previous stage in that large branches are appearing from the stem of the posterior cerebral artery and. running superiorly over the anterior aspect of the mesencephalon, reach and supply the medial and posterior aspects of the cerebral hemispheres, including the posterior portion of the hippocampal area. This large vessel and the choroid vessels are illustrated in plate XVII. Almost the entire region is covered from lateral view by the overlying temporal lobe (depicted as the area lying inferior to the heavily marked line). The vessels are lying medial to the hemisphere, between it and the underlying diencephalon, and are therefore dotted. Only the major branches of the choroid vessels are showing, both originating as they do in previous stages, both running posterior to, then superior to, the stalk of the internal capsule. The major branches shown are the choroid vessels from which the arteries derive their name. The lateral striate vessels are well formed branches of the anterior portion of the internal carotid, much as they are in the adult.
Plate XVIII illustrates the area, as outlined on plate XVI, just inferior and anterior to that shown above. The middle and anterior cerebral vessels are now firmly established in their adult morphology. The middle cerebral artery is seemingly taking over as the major continuation of the internal carotid, much as it does in the adult. The middle cerebral vessel forms a major stalk in the posterior endorhinal fissure, from which lateral striate vessels arise to sink into the brain via the endorhinal fissure and now find their way to the lentiform nucleus, body of the caudate, and the superior aspects of the internal capsule. The middle cerebral vessel then extends beyond the fissure, enters the developing Sylvian fissure in which it branches widely over anterior and lateral aspects of the hemisphere.
The anterior cerebral artery runs medially in the same relationship to the anterior commissure, lamina terminalis and olfactory tubercle and nerve as previously explained. The anterior communicating artery comes off as a short medial stalk to join the anterior cerebral artery of the opposite side. The points of interest as far as this artery is concerned are the two major lateral branches both apieally situated from the anterior communicating artery and both directed into the head of the caudate-putamen mass (figure E9)• This is a duplication of the medial striate artery that would probably persist to the adult stage as abnormal arteries.
Figure El, plane C, is a section through the anterior portion of the mesencephalon, cutting the tip of the hind brain. Around the brain stem as a whole the dura is condensing as a definite covering. Superiorly, streaming through this condensation, is a massive plexus of veins joining the various channels forming in the dura with those draining the roof of the diencephalon. Between the mesencephalon and the hind brain the basilar artery lies as a separate vessel on the anterior surface of the hind bran, while the posterior cerebral stem is forming from mesencephalic branches.
In figure E2, plane D, the section traverses the occipital lobe. The diencephalon is represented ty a thickened dorsal thalamus while the cavity, inferiorly, is the mammilaiy recess. The arteries have separated into the familiar posterior choroidal branch and posterior communicating arteries, running anteriorly over the lateral wall of the diencephalon.
Figure E3, plane E, illustrates the posterior extension of the caudate nucleus in the floor of the temporal lobe, lying immediately lateral to the plexus of the anterior and posterior choroidal vessels, these vessels forming this plexus over the lateral geniculate body of the dorsal thalamus. The straight sinus is a prominent vessel In the roof of the diencephalon. Xnferiorly the internal carotid artery is running superiorly to join the posterior communicating artery, lateral to the hypothalamus• In the right hemisphere there is depicted the narrow stalk of the posterior aspect of the invaginated choroid plexus.
Figure E4, plane F, illustrates the division of the internal carotid into its posterior and anterior divisions at the level of the hypophysis. In this embryo the anterior choroid arises posteriorly near the junction of the internal carotid artery with the posterior communicating vessel. This large junction of vessels is shown in figure E4*
Figure E5, plane F®, illustrates the well formed internal capsule passing from the cortex to the diencephalon via the corpus striatum. The morphology of this region is the same as in the previous stages, except that now a well marked optic chiasma and optic tract extends around the floor and laterally and posteriorly around the diencephalon to end at the lateral geniculate boc^y. The origin of this optic tract is seen in figure E6 as the optic chiasma. Lateral to the hypothalamus, the internal carotid divides into its anterior branches. From there, fairly well marked striate branches are arising although this feature is obscured ty shrinkage.
Figure E7, plane H, is a section through the foramen of Monro, the floor of which is the anterior commissure and the caudate nucleus, still well separated into medial and lateral hillocks. The anterior cerebral artery has moved well medially to the anterior commissure, lying here as two prominent vessels (A.C.A.).
In figure E8, plane H ? , the section has passed just anterior to the lamina terminalis. Ventral to the hemispheres the anterior cerebral vessels are forming the short medial branch, the anterior communicating artexy. The floor of the hemisphere is bulged ty the large head of the caudate-putamen mass, while the choroid plexus fills most of the anterior ventricle.
Figure E9, plane I, shows one of the two large medial striate arteries arising from the anterior cerebral artery and, running laterally, dipping into the caudate head. In doing so it finds itself in a profuse plexus of arteries and veins over the olfactory region.
Figure E11, plane 1% cuts the right hemisphere at the origin of the olfactory nerve and the left hemisphere on a slight bias above this showing the origin of the second medial striate vessel.
Figure E12, plane I Mf , shows the left hemisphere at a slightly lower plane with the origin of the olfactory nerve in view, separating the areas of distribution of the anterior and middle cerebral arteries.
In the floors of the hemispheres there is a slight bulge which indicates the anterior portion of the head of the caudate-putamer; mass.
PLATE XVI (E35 9 original 20X).
This is a photographic reproduction of a graphic reconstruction (lateral view) of the forebrain of a 33*0 msu # C-R lengthy human emfezyo with the more important arteries and veins superimposed• See text
An enlargement of the area outlined as such on plate XVI showing the main branches of the choroidal arteries at the 33 mm*
An enlargement of the area outlined as such on plate XVI showing the arterial distribution of the anterior and middle cerebral arteries around the olf&etoiy region®
FIG. El PLANE G SLIDE 22-3-4 FIG. E2 PLANE D SLIDE 21-1-1
FIG. E3 PLANE E SLIDE 16-3-2 FIG. E4 PLANE F SLIDE 15-3-3
PLANE H SLIDE 9-3-4 FIG. E8 PLANE H* SLIDE 8-3-2
FIG. E9 PLANE I SLIDE 7-3-1 FIG. E10 PLANE I* SLIDE 7-1-3
Summary and Conclusions
The morphology of Mammalian forebrain arteries develops consistently from Fishes and Reptilia in relation to corresponding nuclei. The basic stem upon which this series is based is the division of the internal carotid artery into a cranial division and a caudal one. The earliest vertebrate indication of Mammalian Corpus Striatum is the palaeo—striatum of Fishes which receives its blood supply from both lateral olfactoiy and medial olfactoiy arteries. The hypopallium of the neo-olfactorium receives its blood from the lateral olfactoiy artery.
In Amphibia, the lateral olfactoiy artery appears as three main branches, the striate branch persisting in the endorhinal fissure as the arterial supply to the hypopallium. The pyriform branch relates to the pyriform cortex and the hippocampal branch relates to the hippocampus. The latter relates to progressively posterior branches of diencephalic arteries and forms the root of the human posterior cerebral artery. The anterior cerebral changes position, relating wholly to the palaeo-striatum and the olfactoiy apparatus.
In Reptilia the brain develops the neo-pallium and the caudate and putamen nuclei, the latter from the hypopallium which retains its striate arterial supply from the old lateral olfactoiy artery. The middle cerebral artery appears as a combination of the striate branches and pyriform branches. The anterior cerebral artery has switched its main supply from the olfactoiy lobes to the medial wall of the cerebral hemispheres but maintains branches to the palaeo-striatum, now represented ty the inferior anterior head of the caudate-putamen mass, corresponding region of the internal capsule, tail of the caudate and aiqj^daloid nucleus. In the internal capsule, but retains its basic relationship to blood supply. The anterior head of the palaeo-striatum takes its blood from striate branches of the anterior cerebral, particularly the medial striate artery. The posterior tail of the palaeo-striatum takes its blood from the anterior choroidal artery, a fusion of anastomotic channels, in the Reptilia, between the middle and posterior cerebral arteries in response to the growth of the lateral geniculate body. This latter condition has been one of convenience as the nuclei outgrew their original sphere. The neo-striatum takes practically all of its blood supply from the middle cerebral artery.
In the series of human Embryos, the 12.5 mm., C-R length, stage represents a transitional period for both nuclei and vessels. The palaeo™striatal region is well established, forming the medial hillock and gaining its blood supply from striate branches of the anterior cerebral artery. The neo-striatum forms as the slowly developing lateral hillock and is gaining all its blood supply from the striate branches of the middle cerebral artery. Between the anterior and middle cerebral arteries is a series of anastomoses representing the original network between these arteries over the palaeo-olfactorium.
There is no anterior or posterior extension of the corpus striatum and consequently the morphology of the arterial system does not include channels for these regions. There is no internal capsule. The anterior choroidal artery forms a primitive junction with the posterior choroidal artery, a branch of the posterior cerebral artery, over the lateral geniculate body. There is no evidence of choroid villi in the lateral ventricles. The venous drainage of these regions is well established inferiorly through the striate veins but the superior drainage is marked by the ill defined superior sagittal plexus which dips between the hemispheres.
Elaborations occur in all regions ty the 15 mm. stage. A tremendous expansion of the dorsal thalamus has resulted in a profuse branching of the choroidal arteries over the lateral geniculate body. The velum interpositum has invaginated the medial walls of the hemispheres, forming the choroid villi, which draw major branches from the nearly choroidal plexus. Along the roof of the diencephalon the velum has differentiated the straight sinus and establishes the first evidence of the superior drainage of the corpus striatum. Vessels indiscriminately drain from the choroid plexuses into the straight sinus and caudate extensions drain from the superior corpus striatum through the hemispheric stalk directly into the straight sinus. Inferiorly, definitive features are appearing in relation to the blood supply of the corpus striatum. The latter is being extended anteriorly and posteriorly ly the extending hemispheres. The posterior extension, the posterior aspect of the palaeo-striatum, comes into relationship with the branching anterior choroidal artery and gains its definitive arterial supply from that vessel. The middle cerebral artery reaches its definitive form as a striate stem in the endorhinal fissure and extending ty way of pyriform branches over the lateral aspect of the hemispheres. Its striate branches are constant to the neo-striatum.
The anterior cerebral artery, besides maintaining its striate branches to the palaeo-striatum, is enmeshed in a double set of primitive plexuses. Medially the highly plexiform primordium of the anterior communicating artery joins the anterior cerebral vessels. Laterally, the underlying anterior head of the caudate nucleus draws its blood supply from the primitive anastomosing branches of the middle and anterior cerebral vessels around the palaeo-olfactorium. The anterior medial branch of this series forms the definitive recurrent artery of Heubner* Abnormal arteries, with or without accessory recurrent vessels, may occur as remnants of ary stems of this plexus and arise along the lateral aspect of the anterior cerebral artery from its origin apically to the anterior communicating vessel, and from the anterior margin of the middle cerebral vessel from its origin to the Sylvian fissure*
At the 20 mm* stage the internal capsule imperfectly divides the corpus striatum so that it assumes its adult morphology. Also, by this stage the definitive morphology of the circle of Willis and its important brandies are established in all important aspects. The anterior choroidal artery is forced into a posterior arch by the hemispheric stalk as the artery ascends to its distribution in the choroid plexus. In so doing it establishes its definitive supply to the tail of the caudate nucleus, anygdaloid nucleus, posterior aspect of the globus pallidus and the inferior portion of the posterior limb of the internal capsule. The middle cerebral artery extends its pyriform branches but is constant from the previous stage* The lateral series of anastomoses between the middle and anterior cerebral vessels is being replaced ty a network of fine vessels and a major branch, the medial striate artery* The medial plexus is also being replaced iy a single branch, the anterior communicating artery. The anterior drainage of the straight sinus has elaborated the internal cerebral veins which drain each hemisphere separately* Both caudate veins and choroid veins drain separately anteriorly into the straight sinus, in the roof of the Foramen of Monro, turn posteriorly as the internal cerebral veins which join to form the single vein of Galen.
The 25 mm. stage illustrates some of the abnormalities possible in the morphology of the circle of Willis. The posterior track of the posterior cerebral artery is represented ty the posterior communieating artery which represents a dwindling contact with the original source of blood supply, the internal carotid artery. This artery may remain in a primitive state, transitional, or dwindle completely. Also striate branches may enlarge to form accessory choroidal vessels or provide abnormal origin of choroidal arteries along the arterial tract from the middle cerebral artery, internal carotid, posterior communicating, posterior cerebral and even the basilar artery.
The lateral series of anastomoses between the anterior and middle cerebral arteries persists to the 25 mm. stage and indicates that a persistence of these vessels might be the most common abnormality of the recurrent artery of Heubner. The series of vessels from the middle cerebral artery usually does not persist. Abnormalities of the recurrent artery are usually associated with abnormalities involving either the anterior cerebral artery, the anterior communicating artery or all three. If the recurrent artery is doubled, usually the proximal portion of the anterior cerebral artery is absent, or the anterior communicating artery remains plexiform. The recurrent artery also may be composed of three or four branches or arise as a spray of small vessels. The anterior communicating vessel may present abnormalities involving only itself, such as doubling, tripling and retention of various forms of the original plexus form, or complete absence of the vessel^ in which case the medial aspect of the anterior cerebral arteries is usually fused for a vaiying distance.
By the 25 mm® stage venous drainage extends to the regions supplied ly both choroidal and striate arteries. The posterior terminal vein lies in the terminal sulcus draining both thalamus and the superior aspect of the caudate nucleus.
The morphology of the circle of Willis is little changed in the 33 nun. stage, the vessels as laid down responding to the needs of a rapidly expanding forebrain.
1. Abbie. A. A, 1933 J. Anat. Lon. 67:491-421.
1933 Clinical significance of the anterior choroidal artery. Brain. Vol. 56:233-246.
1934 Forebrain arteries and evolution of the basal ganglia. J. of Anat. Vol. 68:433-470.
2. Aiken and Ayer 1907 Boston Medical and Surgical Journal. Vol. 156:768-769.
3. Alexander. L. 1942 Vascular supply of the strio-pallidum. Assoc. Res. Nerv. and Ment. Bis. Proc. Vol. 21:77-132.
1933 Alexander and Putman, T. J. Pathological alterations of vascular patterns. A. Res. Nerv. and Ment. Bis. Proc. 18: 471-543.
4. Bailey. P. 1916 Morphology of the roof plate of the forebrain and the lateral choroid plexus in the human Embryo. Jour. Comp. Neur. Vol. 26:79-120.
5. Bassett. R. C. 1951 Arterovenous anomalies of the brain. J. Neurosurgery. Vol. VIII, No. 1, p. 59.
6. Beevor. C. E. 1909 Arteries of the human brain. Phil. Trans. Roy. Soc. Lond. B. Vol. 200:1-56.
1907 The cerebral arterial supply. Brain 1907:30-406.
7. Bremer. J. L. and Weatherford. H. L. 1944 A textbook of histology arranged upon an embyological basis. Ed. 6.
1943 Congenital aneurysms of the cerebral arteries - an embryonic study. Arch. Path. Vol. 35; 319-331.
8. Carpenter. Malcolm, B,. and Noback, C. R. 1954 The origin and distribution of the anterior choroidal artery. The Anat. Record. No. 2. VoL 118: A.M.A. Arch, of Neu. and Psych. June 1954* Vol 71, no. 6:714-722.
9. Chalkey. H. W. 1943-44 A method for the quantitative morphological analysis of tissues. J. Nat. Cancer Institute 4?47.
10. Congdon. E. B. 1922 Transformation of the aortic arch system in the development of the human embryo. Carnegie Inst. ¥ash. Pub. 277, "Contributions to Embryology" Vol. 14:47-110.
11. Cooper. E. R. A. 1946 Development, of the human red nucleus and the corpus striatum. Brain 69:34-44*
12. Cox, L. B. 1952 Congenital vascular malformations of the brain. Medical Journal of Australia (Sydney) 2:16 p. 540-541.
13. Craigie, E. H . 1929 Anat. Rec. 43 193S Vascularity in brain of frog. J. Comp. Neur. 69:453-470.
1941 J. Comp. Neur. 74.
1930 Anterior cerebral artery and syndromes. Brain. Vol. 53: 120-165.
Dandy, E. 1944 Intracranial arterial aneurysms. Ithaca N.Y. Comstock Publishing Co. Inc. VIII p. 47-215.
Dart, R. A. 1935 Evolution of the corpus striatum. J. Anat. 69:3.
1920 A contribution to the morphology of the corpus striatum. J. Anat. Vol. LV p. 1.
DeGaris, F. C. 1924 Am. Join*. Physic. Anthrop. 7:95*
Dendy, A. 1909 Intracranial vascular system of Sphenodon. Phil. Trans. Roy. Soc. Sec. B. Vol. cc p. 403*
Drummond, S. P. 1944 A comparison of the Injection and Red Cell staining methods used in quantitative studies of the capillaries of the Central Nervous System. Anat. Rec. Vol. 89: p. 93* 1944*
Encyclopedia of Histological Techniques.
1944 A method for visualizing the blood vessels of nerves and other tissues. Anat. Rec. Vol. 89:65. 1944*
Fetter-man, G. H., and Moran, T. J. 1941 Anomalies of the circle of Willis in relation to cerebral softening. Arch. Path. 32:251-257. Aug. *41*
Foley. J. M., Kinney, T. D., Alexander, L. 1942 Vascular supply to the hypothalamus in man. J. Neuropath, and Exp. Neurol. 1:265-296. Freedman, W.
1953 Hazards of lobotoiry. A.M.A. Arch, of Neur. and Psych. (Chic.) 69:5 p. 640-3.
25. Fulton 1950-51 Frontal lobotony and affective behaviour, W. L. 370 f. 97 (m). (Withering Lectures).
26. Gedeon. Eros 1941 Method for fuchin staining of the network of cerebral blood vessels. Arch, of Path. 31:215, 1941.
27. Gilbert. M. S. 1935 The ear3y development of the human diencephalon. Jour. Comp. Meur. Vol. 62:81-115.
28. Godinov. V. M. 1929 The arterial system of the brain. Am. J. Physic. Anthrop. 13:359.
29. Goldty, F. 1934 Blood supply to the corpus striatum (lizard) . Jour. Anat. 68:159.
30. Gomori. G. 1939 Microtechnical demonstration of phosphatase in tissue sections. Proe. Soc. Exp. Biol, and Med. 42:23 1939.
31. Gurdjian. E. S. 1928 Corpus striatum in the rat. J. Comp. Neur. Vol. 45:249-282.
32. Halkern, M. H. 1953 A method of graphic reconstruction in isometric perspective. Anat. Record. (Phil.) 116:1 p 1-7 May 1953.
33. Hamilton. W. J.. Bgyd, J. D., Mossman. H. W. 1952 Human Embryology, Second Ed. pp. 289-302.
34. Harrison. C. F... Luttnell, C. 1953 Persistent carotid-basilar anastomosis. J. Neursurg. 10:3 P 205-15* May 1953*
35. Harrison, B. G. 1935 Origin and development of the nervous system, by experimental embryology. (Croonian Lecture). Proc. Roy. Soc. 1935, USB: 155-196.
36. Herrick. C. J. 1930 Brains of rats and men. Chicago p. 103•
1931 An introduction to neurology.
37. Hines. M. 1922 Studies in the growth and differentiation of the telencephalon in man. Jour. Comp. Neur. Vol. 34:73-171.
1922-23 Development of the telencephalon in Sphenodon. J. Comp. Neur. Vol 35:482.
38. Holmgren, N. 1922 ( 23) Points of view concerning forebrain morphology in lower vertebrates. J. Comp. Neur. Vol. 34-35:391.
39. Johnstone 1910 Evolution in the cerebral cortex. Anat. Record. Vol. 4:143
1918 Histology of caudate nucleus and stria terminalis in vertebrates. Anat. Record. Vol. 14
1923-24 J. Comp. Neurol. 35:337. J. Comp. Neurol. 36:143.
40. Kappers. C.U.A. 1924 Jour. Anat. 58:181.
41. Keith. A. Sir 1947 Human Embryology and Morphology p. 156.
42. Kleiss, E. 1942 Various forms of the circle of Willis, a statistical study. Anat. Anz. 92:216-230 Jan. 8, 1942.
43. Kodama. J. 1926 Uber die sogenannten Basalganglien. Schweizer Archf. Neur. U. Psych. Bd. 18, 5. 169-241, Bch 19, 5. 152-177.
44. Kull. H. A. 1925-26 Staining for contained blood. Anat. Rec. Vol 31-33.
45. Lee. A. B. Lee*s Vade-Mecum 7th Ed. (Gilson®s rapid celloidin process).
46. Lesem. W. H. 1905 The comparative anatony of the anterior cerebral artery. The Post Graduate 1905-20:455-
47. Mall. F. P. 1912 Keibel and Mall, Manual, Vol. 2:570-709.
48. Meek. W. J. 1907 A stucjy of the choroid plexus. Jour. Comp. Neur. Vol. 17: 286-306.
49. Padget, D. H. 1948 Development of the cranial arteries in the human Embryo. Contributions to Embryology. Vol. 32. Nos. 207 to 212. Carnegie Inst, of Wash. Pub. 575-
50. Papez. J. W. 1940 Embiy©logical development of the hypothalamic area in mammals. Ass. Res. Nerv. Ment. Dis. Proc. 20. Williams & Williams, Baltimore.
51. Parker. G. H. 1909 Phylogenetic origin of the nervous ^rstem. Anat. Record. Vol. 4:51-
52. Patten, B. M. and Philpot. R. 1921 The shrinkage of Embryos in the process preparatoiy to sectioning. Anat. Rec. 20:393- 1921.
53. Rogers, L. 1947 Function of circle of Willis. Brain 70:171-178 June ®47.
54. Rubenstein, H. S. 1944 Relation of the circle of Willis to the hypothalamus and internal capsule. Arch. Neurol, and Psychiat. 52:526-530. Dec. f 44.
1944 The anterior communicating artery in man. J. Neurpath. and Exp. Neurol. Vol. 111:196-198.
55. Saphir, 0. 1935 Defects in the circle of Willis. Am. J. Path. 11:775.
56. Scharrer, E. 1940 Arteries and veins in the mammalian brain. Anat. Record 78:173-196 Oct. 25 *40.
1950 Anat. Record 107:319 July 1950.
57. Schepers. G. W. H. 1938 Blood supply to the corpus striatum (tortoise). J. Anat. 72:535.
1939 Evolution of the forebrain. J. Anat. Lond. 73:451.
58. Schlesinger, B. 1939 Venous drainage of the brain with special reference to the Galenic system. Brain 1939, 62:274-291.
59. Schmidt 1950 Recent studies in cerebral circulation. Harvey Lectures 44s 124-144. 1950.
60. Shaner, R. F. 1932 Development of the nuclei and tracts of the midbrain. J. Comp. Neur. 55:493.
1936 Development of the globus pallidus in pig. J. Comp. Neur. 64:213.
61. Shell shear. J. L. 1920 The basal arteries of the forebrain and functional significance. Jour, of Anat. Vol. 55:27-35.
1930 A. Phil. Trans. Rcy. Soc. London B. Vol. 218:11-36.
1930 B. Journ. Anat. Vol. 65:45-87.
62. Smith. Q.E. 1919 Morphology of the corpus striatum and origin of the neopallium. J. Anat. Vol. LIII:271.
63. Streeter, G. L. 1918 Formation of arteries from the capiilaiy network. Carnegie Wash. Pub. 271, Cont. to Embryo. Vol. 8:5-38 (No. 24).
1942 Developmental horizons. Cont. to Embryol. 541 Vol. 30:211.
1945 Carnegie 557. Cont. to Embryo. Vol. 31:27-63*
1948 Carnegie 575 Cont. to Embryo. Vol. 32:133-203*
64. Strong, and Elwyn. 1948 Human neuroanatony - Definitive blood supply to the brain, p. 394.
65. Sunderland , S, 1948 Neurovascular relations and anomalies at the base of the brain. J. Neurol., Neurosurgery and Psychiat. 11:243- 257 Nov. *48.
66. Tichy, Fae. 1949 Syndromes of the cerebral arteries. Archives of Path. 48 (5):475.
67. Watts. J. W. 1934 A comparative stuc^ of the anterior cerebral artery and the circle of Willis in Primates. J. of Anat. 68:534- July 1934.
68. Williams, D. J. 1936 Development of the cerebral cortex and its vessels. Brain 59.
69. Wishlocki, G. B. 1936 Hypophysis and hypothalamic blood supply. Ameri. Jour, of Anat. Vol. 58:421-472.
1937 Embryonic study of blood vessels of human hypophysis. Ameri. Jour, of Anat. Vol. 61:95-129*
70. Young. A. F. and Karnosh, L. J. 1949 Anterior perforating arterioles and their relation to the internal capsule. Dis. Neu. Sjystem 10:99 April 49.