Paper - The nervous and vascular relations of the pineal gland (1940)
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le Gros Clark WE. The nervous and vascular relations of the pineal gland. (1940) J Anat. 74(4): 471-492. PMID 17104831
Møller M. (1978). Presence of a pineal nerve (nervus pinealis) in the human fetus: a light and electron microscopical study of the innervation of the pineal gland. Brain Res. , 154, 1-12. PMID: 698804 DOI.
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The Nervous and Vascular Relations of the Pineal Gland
By W. E. Le Gros Clark
Department of Anatomy, University of Oxford
From time to time anatomists have drawn attention to obvious analogies which exist between the epiphysis and the neural part of the hypophysis. Both are developed as diverticula of the diencephalon, both are characterized by cellular elements which are believed to represent a modified type of neuroglia and whose processes have special relations with the walls of blood-vessels, both are apparently related by nerve fibres to adjacent cell collections in the hypothalamus or epithalamus, and there is some evidence to show that both have a secretory function of some kind.
In recent years the nervous and vascular relations of the hypophysis have been studied in considerable detail by the examination of normal material and also by experimental methods. A special vascular relationship between the hypophysis and certain groups of cells in the hypothalamus has been described by Popa & Fielding (1930) and also by Basir (1932), though the conclusions of these authors have been criticized and modified by the more recent researches of Wislocki & King (1986). The existence of efferent fibre connexions from certain cell groups in the hypothalamus (particularly the nucleus supraopticus) has been affirmed by the study of normal silver preparations, and confirmed by experimental anatomical methods and by the study of clinico-pathological material. It therefore becomes a matter of some interest to determine whether the pineal gland is related in a similar way to the epithalamus.
The present investigation was initiated with the study of the pineal gland of the rhesus monkey, of which abundant material has been available in this laboratory. Certain observations on this material led to a further study of the human pineal gland and adjacent structures, and the specimens used for this purpose have been obtained at necropsies.
Material and Methods
For the study of the nervous relations of the pineal gland the following macaque material has been used:
(a) Stained with Bodian’s protargol technique.
(1) Sagittal serial sections of the pineal gland and adjacent part of the brain.
(2) Horizontal serial sections of the pineal gland and adjacent part of the brain.
(3) Sagittal serial sections through a block containing the pineal gland and the whole length of the straight sinus.
(4) Horizontal serial sections through a similar block.
(b) Stained with pyridine silver.
(5) Sagittal serial sections through the pineal gland and adjacent part of the brain.
(6) Sagittal serial sections through a block containing the pineal gland and the whole length of the straight sinus.
(c) Stained by Stöhr’s modification of Schultz’s silver impregnation method.
(7) A spread preparation of the tissue connecting the apex of the pineal gland to the straight sinus.
(d) Stained with intravitam methylene blue (0-05 %).
(8) and (9) Spread preparations of the pineal gland, straight sinus and adjacent membranes, cleared in oil of wintergreen.
In addition (10), sagittal serial sections of human material (stained by Bodian’s method) were prepared from a block containing the pineal gland, the anterior end of the straight sinus, and the intervening tissue.
For the study of the vascular relations of the pineal gland in the macaque monkey the following material was prepared:
(e) (11) and (12) Thick frozen sections of the pineal gland and adjacent part of the brain, in which the blood-vessels were demonstrated by the use of the nitroprusside benzidene method as elaborated by Pickworth (1934). Two such preparations were made.
(f) Carmine-gelatin injection.
(13) In one animal in which the whole body had been injected, the pineal gland and adjacent tissues were removed, dehydrated, and cleared in oil of wintergreen.
(g) Stained with haemotoxylin and eosin.
(14) and (15) Serial sagittal sections through blocks containing the pineal gland and the whole length of the straight sinus.
(16) Thick celloidin sections through a block containing the pineal gland, anterior end of the straight sinus and adjacent tissues.
Lastly, from human material, serial celloidin sections (cut alternately at 30 and 150 u) were prepared from a block containing the pineal gland, anterior end of the straight sinus, and adjacent tissues. These were stained with haemotoxylin and eosin, except for a few selected sections which were stained with Van Gieson’s stain and orcein.
Many neurohistologists have recognized the presence of nerve fibres, myelinated and unmyelinated, in the pineal gland of mammals. It is now generally accepted (Hortega, 1932) that these fibres are derived from three sources: (a) sympathetic plexuses accompanying the arteries in the adjacent part of the tela chorioidea, (b) habenular commissure, and (c) posterior commissure. This statement is in accord with observations published by Darkschewitz (1886), Favaro (1904), Marburg (1909), Pastori (1928), Cutore (1910), Walter (1914), Achicarro & Sacristan (1912), Josephy (1920), Pines (1927), Antonow (1925), etc. Some anatomists have suggested definite nuclear and fascicular origins for the fibres which enter the pineal gland from the habenular and posterior commissures—such as the habenular ganglion, the tectum of the midbrain, the fasciculus retroflexus, the taenia thalami, the intercalary tract, and even (Darkschewitz) the optic tract. Perhaps the most ambitious account of the fibre connexions of the gland is that recently provided by Roussy & Mosinger (1938), in which they attempt to bring the structure into their scheme of the “‘neuro-endocrine” system of the diencephalon, and to link it up functionally and anatomically with the neural lobe of the pituitary gland. According to this account, the fibres in the pineal gland are derived from (among other sources) the habenular ganglion, the anterodorsal nucleus of the thalamus, the nucleus tangentialis accessorius, the preoptic area of grey matter, the periventricular grey matter of the thalamus, and the superior and inferior colliculi. Such conclusions appear to be based entirely on the casual inspection of sections of normal material; for this reason they must be regarded as entirely uncertain, simply because there is no possibility in such sections of tracing individual fibres in continuity over these distances. In regard to the distribution of nerve fibres within the substance of the pineal gland, there has been some difference of opinion. Cutore, for example, described the commissural fibres as spreading out into the pineal parenchyma in a fan-wise manner to contribute to the formation of the plexus in the main part of the gland and almost reaching its apex, while Walter supposes that the epiphysis contains but a small component of fibres from the habenular and posterior commissures. On the other hand, Cajal takes the view that the nerve plexus in the main body of the gland is entirely derived from sympathetic fibres accompanying the chorioidal vessels. Those fibres which previous authors had attributed to a commissural origin are really derived, according to Cajal, from plexuses accompanying inferior pineal arteries which enter the gland near its base and are directed distally. Incidentally, Cajal recorded a very rich plexus of nerve fibres in the pineal gland of the mouse, and he described their terminal ramifications as forming an extremely fine network surrounding clusters of pineal cells and recalling in appearance the nerve plexus found in the pancreas and salivary glands. On the other hand, Antonow (1925), studying the pineal gland of the dog, cat, rabbit and deer, was unable to find the dense network of fibres described by Cajal, and supposed that the latter had misinterpreted the appearance of reticular connective tissue fibres. Such a criticism, in view of Cajal’s great reputation, appears likely to be unfounded. Pines (1927) has more recently described and figured nerve endings in the pineal gland of the dog, showing minute end-bulbs apparently related to the parenchymatous cells. Also, since he found that the terminal network has no direct relationship with blood-vessels, he concludes that it represents part of a nervous apparatus which stands in immediate relation to the specific functions of the epiphysis—in other words, it is composed of secretory fibres.
- 1 In the literature the word “conari’’ is used, but this is clearly incorrect.
When silver-impregnated sections of the macaque pineal gland (which had been prepared for the present study) were first examined, numerous cells were found in the centre of the gland of whose nervous nature there could be no doubt (PI. II, fig. 3). This observation occasioned some surprise, since it is generally supposed that true nerve cells are not to be found within the substance of the epiphysis except as occasional heterotopic elements (Hortega, 1982). The cells are relatively large, usually multipolar (but sometimes bipolar), and give rise to numerous branching processes. They are mainly collected in the centre of the distal half of the pineal body and are here embedded in a mass of neuropil which forms a central core to the gland (Pl. I, fig. 2). Occasional cells of a similar type are also to be found in the proximal half of the gland.
A reference to the relevant literature showed that these nerve cells had been previously recognized and described. Kolmer (1929) recorded the presence of relatively large nerve cells in three species of monkey, Macaca mulatta, M. sinica, and Papio cynocephalus. He found that they were embedded in a layer of neuroglia and connective tissue in the distal part of the pineal gland, and from this region he was able to trace myelinated fibres, accompanying small blood-vessels, towards the tip of the gland where they emerge on the surface. Here the fibres form a well-defined bundle, lying in relation to the vena magna cerebri, which Kolmer (in collaboration with Loewy, 1922) had previously described in certain lower mammals (i.e. guinea-pig, dog and goat). This nerve bundle has been named the nervus conarii,! and it was Kolmer and Loewy who first suggested that it contains efferent fibres whose cells of origin lie in the pineal gland itself. Later the nerve was studied by Pastori (1930), who recorded it in the dog, cat, sheep, monkey and man. He also described as a constant feature in all these species a circumscribed group of small nerve cells situated in the pial tissue close to the tip of the pineal gland, and which he termed the ganglion conarti. In a series of nine human brains he claims to have identified this ganglion, and states that it contains about twenty nerve cells, closely packed, and 15-20, in size. Unfortunately Pastori does not in his paper offer a photomicrograph for inspection to show the appearance of these cells. It may be noted, however, that a ganglion in this position was described many years previously by Marburg (1909) in the brain of a new-born infant, and this author compared it to the parietal ganglion of reptiles.
More recently, a short paper has appeared by Levin (1988) calling attention once more to the presence of numerous ganglion cells within the pineal parenchyma of monkeys (Macaca mulatta, M. radiata, Ateles ater, and Alouatta seniculus). In the bonnet monkey a count showed the number of ganglion cells to be approximately 2000.
Apart from monkeys, however, no true nerve cells have been certainly identified in the substance of the pineal gland except possibly as occasional heterotopic elements, and according to Pastori they are also absent in the chimpanzee and in the marmoset (Hapale jacchus). The possibility at once suggests itself that the intrapineal ganglion cells of monkeys represent the ganglion conarii of Pastori which has become secondarily incorporated within the substance of the gland instead of occupying the usual position in the pial tissue at its apex. However, the cells within the macaque pineal gland appear to be much more numerous and also considerably larger than those described in the ganglion conarii of other mammals by Pastori.
As already noted, the silver-impregnated macaque material which was prepared for the present study has fully confirmed the presence of many ganglion cells in the pineal gland of these animals. The cells show no regular orientation, most of them give off a number of stout branching processes which contribute to and are soon lost in the dense plexus of nerve fibres in which they lie, and in general appearance they bear a close resemblance to the nerve cells found in peripheral ganglia of the autonomic nervous system. The central core of neuropil in the macaque epiphysis is very vascular, and herein a marked contrast is shown with the more proximal part of the gland where the vascularity is by no means rich. The vascular plexus related to the central core of neuropil may be seen by reference to Pl. I, fig. 2, where the capillary vessels are seen as clear areas in the mass of interlacing nerve fibres. It is also quite well shown in ordinary haemotoxylin and eosin sections. In the specimen of the macaque pineal in which the blood-vessels had been injected with carmine gelatin, it is perhaps most clearly evident. Here the closely meshed capillary plexus can be seen to occupy a circumscribed area in the distal half of the gland, corresponding in position to the core of neuropil which had been demonstrated in other specimens by silver impregnation. The plexus receives its main contribution from a leash of fine vessels entering the pineal gland at its apex (to which future reference will be made), but it also receives accessions from vessels lying on the surface of the distal half of the gland and penetrating the latter from the lateral aspect. The high vascularity of the neuropil core is presumably related to the level of its metabolic activity, and, in view of recent studies by Dunning & Wolff (1937), the existence within this network of synaptic arborizations seems probable. It is interesting to note, also, that in the same region of the pineal gland in the monkey thick sections show a local accumulation of large and elaborately branching melanocytes, filled with dark brown pigment (Text-fig. 1). The presence of melanin pigment in the pineal gland of mammals is well recognized, and Roussy & Mosinger (1938) have recently made use of this observation to extend their conception of “pigmentary neurocrinie”’.
We may now consider the origin of the nerve fibres which can be seen in silver-impregnated sections to penetrate the pineal gland and apparently to take part in the formation of the network of nerve fibres within its substance. These fibres may conveniently be divided into three groups: (a) those which enter from the lateral aspect of the gland in company with blood-vessels, (b) those which enter by way of the peduncle of the gland, and (c) the conspicuous fasciculus which can be seen emerging from (or penetrating) the apex of the gland.
(a) The small arterioles which enter the surface of the pineal gland in the monkey are particularly well supplied with nerve fibres which run in. close contact with them; indeed, their innervation is considerably more rich than that of cerebral vessels entering the brain substance. They are essentially components of the chorioidal system of vessels, being terminal branches of the posterior chorioidal arteries, and it has previously been emphasized (S. L. Clark, 1934) that vessels supplying chorioidal plexuses have an abundant nerve supply. Within the gland, vascular nerve fibres frequently run as discrete fasciculi in direct relation to the blood-vessels, and many of them become lost in the central nerve plexus so that their ultimate destination cannot be determined. The sections provide no evidence that any of the fibres have a direct terminal relation to the parenchymatous cells of the epiphysis.
Text-fig. 1. Thick sagittal section of the pineal gland of a rhesus macaque, showing the distribution of melanocytes in the parenchyma. Above is the dorsal sac containing tufts of chorioidal tissue. To the left is seen the vena magna cerebri receiving a small venous tributary from the pineal gland. x 17.
(b) Sections of the pineal gland stained with silver nitrate seem to confirm the observations of many workers that bundles of fibres from both the habenular and posterior commissures contribute to the innervation of the parenchymatous tissue of the gland. These bundles are also to be seen in Weigert sections, particularly in the pineal gland of larger mammals, and they give the appearance of breaking up into a somewhat diffuse radiating network terminating in the proximal part of the gland. A closer study of serial sections, however, indicates that this appearance may be quite illusory.
The fibres entering the pineal peduncle from the habenular commissure arise in part from cells of the habenular ganglion. Of this there can be little doubt, for processes of the cells can be seen to pass directly into the fasciculi which contribute to the formation of the commissure. Other fibres are probably derived from the taenia thalami and may have a more distant origin.
There can be no question of the fact that fasciculi of these commissural fibres enter the proximal part of the gland. If, however, individual fasciculi are followed section by section, in some instances they can be observed to arch medially, and then to run down and leave the gland again, rejoining the habenular commissure on the opposite side. In their course the individual fibres of these fasciculi may become frayed apart by the pineal cells among which they course, subsequently reforming again into a discrete fasciculus. It is thus apparent that these fibres have no terminal relation to the pineal parenchyma—they are merely aberrant commissural fibres. The question now arises whether this interpretation is true of all the fibres of the habenular commissure which can be seen in individual sections to enter the gland. This is clearly difficult or impossible to prove. But it appears certain that, in the embryonic outgrowth of the pineal diverticulum, certain fibres of the habenular commissure have become caught up and displaced, so that they come to pursue an aberrant and broken-up course among the parenchymatous cells of the gland, and it is not improbable that all the nerve fibres which are seen to enter the proximal part of the epiphysis are of this nature. Some of the fasciculi of the commissural fibres, however, meet and become merged with vascular nerve fibres which enter the gland at a higher level and are directed downwards. In this case, an appearance of continuity may have led many observers to affirm that fibres of the habenular commissure extend throughout the greater part of the pineal gland, and actually terminate therein.1 Incidentally, it is possible that the “nervus parietalis”, described by Marburg (1920) in the ventral wall of the suprapineal recess of an antelope, is simply a part of the habenular commissure which has been drawn out into a much elongated loop by the outgrowth of this sac during its embryological development.
The true relation of the posterior commissure to the pineal gland appears to be the same as that of the habenular commissure. Its fibres are drawn up into the posterior wall of the pineal recess, and reach into the base of the gland. Among them may also be found a few small fusiform nerve cells—evidently heterotopically displaced cells from the nucleus of the posterior commissure. Although vascular nerve fibres descending in the gland become intermingled with posterior commissural fibres, a careful study of the serial sections makes it appear probable that the commissural fibres loop up only to return to the opposite side of the posterior commissure, and play no part in the innervation either of the pineal parenchyma or of the vessels of the pineal gland. There is one certain exception to this general conclusion—a few fibres from the posterior commissure leave the aberrant fasciculi and ramify immediately beneath the ependymal epithelium lining the posterior wall of the pineal recess. These really appear to be terminal fibres, and they show a characteristic regular beading along their course just before they terminate, as well as a minute end-swelling. Similar bulbs have been described by Pines (1927) on nerve fibres in the substance of the pineal gland in the dog, and he regards them as evidence of a secreto-motor function. In our own material, such bulbs can also be seen here and there on fibres in the pial tissue investing the gland, and in the pial septa within the gland. But where they have at first sight appeared to be present on fibres lying in relation to parenchymatous cells, this appearance has been found on more careful examination to be illusory only, and due either to a sudden bend or kink in a nerve fibre (simulating a local or terminal thickening), or to the superimposition of a fibre on the darkly stained nucleolus of one of the cells.
- 1 It is relevant to note that in other parts of the brain the displacement to an aberrant position of some of the fibre components of a single tract has on occasion certainly led to a similar misinterpretation. This is the case, for example, with the so-called “anterior accessory optic tract”, an also with fibres of the optic chiasma which may turn dorsally into the periventricular region of hypothalamus.
The general conclusion to be drawn from this study, i.e. that the fibres of the habenular and posterior commissures which enter the pineal gland are merely aberrant commissural fibres, and have no functional relation to the . pineal parenchyma, is consonant with certain other observations. Herring (1927) has drawn attention to the fact that in the rat the pineal gland is separated by some distance from the region of the habenular and posterior commissures, and in this case fibres from the latter apparently do not reach the substance of the gland at all. The same is the case for detached lobules of the gland which may occasionally be seen in other animals. In the serial sections of the pineal region of the human brain prepared for this study by silver impregnation, a small isolated lobule of pineal tissue was found embedded in the dorsal wall of the vena magna cerebri some distance from the main gland, and a study of the sections showed no nerve fibres entering it from the latter. Lastly, even those observers who have convinced themselves that the commissural fibres do in fact terminate in the gland in most cases agree that these fibres only reach the proximal part. It would be unusual, however, for the proximal part of the pineal parenchyma to receive a secretory nerve supply different from the distal part, since its intrinsic structure is everywhere the same.
(c) Silver-impregnated serial sections of the pineal gland of the macaque monkey show that from the central core of neuropil a strong fasciculus of nerve fibres proceeds distally to the apex of the gland and there leaves the latter to course back along the ventral wall of the vena magna cerebri (PI. I, fig. 1). In this situation it is enclosed in a connective tissue sheath (derived from the pia mater), and in appearance and compactness, as well as in the presence of neurilemma cells, it resembles a peripheral nerve. Reference to the literature shows that this nerve bundle is identical with that described by Kolmer and Loewy under the name nervus conarii. The origin and direction of this nerve are quite uncertain. The sections suggest that its fibres may be efferent with respect to the gland, and that they may be derived from the axonal processes of the ganglion cells already described. Such an. inference, however, requires experimental investigation in order to allow of certainty. The fibres are, at least in part, myelinated, and as Levin (1938) has pointed out, this suggests that they are not derived from the cervical sympathetic ganglia, since post-ganglionic fibres are commonly unmyelinated.
The further course of the nervus conarii was studied by three methods: (1) by following it under the dissecting microscope in the tissues of this region which had been removed from monkeys stained intravitally by the injection into the circulation of 0-05 % methylene blue, (2) by the examination of silverimpregnated serial sections of a block containing the pineal gland, the whole length of the straight sinus, the vena magna cerebri, and immediately adjacent tissues, and (3) by tracing the fibres in spread preparations stained by Stéhr’s modification of Schultz’s silver impregnation method.
Text-fig. 2. Drawing of a dissection showing the nervus conarii in a rhesus macaque. The tissues were stained by the intravitam injection of methylene blue. From the tip of the pineal gland fasciculi of nerve fibres extend into the wall of,the straight sinus (which has been opened up from the left side) and here lie in close relation to branches of a chorioidal artery. x30 (approximately).
Two methylene-blue preparations were made, and Text-fig. 2 represents a drawing made of one of these with the aid of a binocular dissecting microscope. The nerve was readily found by this method, issuing from the top of the pineal gland as a well-defined strand. This was teased apart from the tissues in which it lay, and it could be followed running a slightly plexiform course to the commencement of the straight sinus. Here it gave rise to branches which entwined a small arteriole in this region (a branch derived from one of the posterior chorioidal vessels), and some recurrent twigs which followed the arteriole and one of its branches. The nerve then entered the dural wall of the straight sinus and could be followed for some distance in a subendothelial position—always in fairly close relation to the arteriole (which was also found to ramify in the wall of the sinus—vide infra). The subsequent course of the nerve could not be followed further in these preparations owing to the density of the dura mater.
In the silver-impregnated serial sections, the strand of nerve-fibres recognized in the dissections can be seen as a circumscribed bundle emerging from the tip of the pineal gland and passing backwards in close relation to the ventral wall of the vena magna cerebri (PI. I, fig. 1). In its course towards the commencement of the straight sinus it is seen to break up into a plexiform arrangement of fasciculi intimately related to a leash of fine blood-vessels which run down to enter the tip of the pineal gland. It thus appears that the nerve fibres may be primarily vasomotor in type, and this possibility is certainly suggested by their appearance in a spread preparation stained by Schultz’s silver-impregnation method. In this preparation, which is illustrated in Textfig. 8, the strand of tissue connecting the apex of the pineal gland with the tentorium cerebelli has been teased apart, and the blood-vessels and nerve fasciculi have been separated instead of forming a compact bundle. To the left of the figure is the apex of the pineal gland, and here the nerve fibres, splayed apart, can be seen emerging alongside the vessels. To the right is the dense dural tissue at the commencement of the straight sinus, into which the nerve fibres disappear. The opacity of the dura mater prevents them from being followed further.
Text-fig. 3. Drawing of a spread preparation of the tissues extending from the tip of the pineal gland to the anterior end of the straight sinus in a rhesus macaque, stained by Stéhr’s modification of Schultz’s silver-impregnation method. In the drawing the apex of the pineal gland is to the left and the dural wall of the straight sinus to the right. The fasciculi of nerve fibres are seen to be closely associated with small blood-vessels which descend to the tip of the gland. x 60 (approximately).
Reverting once more to the silver-impregnated serial sections of the macaque pineal and adjacent tissue, it can be seen that bundles of fibres derived from the nervus conarii actually run distally for a considerable distance in the wall of the straight venous sinus, occupying here a subendothelial position (Text-fig. 4). They are frequently accompanied by small arterioles, and it is thus possible that they are related functionally more directly to these vessels than to the straight sinus itself. While the preparations are not adequate for the demonstration of the finer nerve endings, in some sections there is to be seen in the connective tissue between the pineal gland and the straight sinus a globular | network of nerve fibres closely similar to the tangled skeins of varicose fibres which S. L. Clark (1934) describes as nerve endings in the chorioid plexus, and which he likens to Meissner’s corpuscles.
Text-fig. 4. Transverse section through the anterior end of the straight sinus of a rhesus macaque, stained by Bodian’s protargol method. A fasciculus of nerve fibres occupying a subendothelial position is shown in the wall of the sinus. x 200. s.s.=lumen of straight sinus.
Whatever the true nature may be of the nervus conarii in the macaque monkey, it seems certain that it is closely related to the blood-vessels of the pineal gland and adjacent tissues, and it becomes necessary to enquire into the origin and course of the latter, with particular reference to the arterial twigs which run up from the region of the pineal gland to enter the dura mater in the wall of the straight sinus.
In the course of dissections of the pineal gland of the monkey, including both injected and uninjected specimens, it was found to be vascularized entirely from chorioidal vessels derived eventually from the posterior cerebral arteries. As seen in Text-fig. 5, on each side a chorioidal artery runs distally in close relation to the lateral surface of the gland. In its course, it gives off two or three small branches which may either penetrate the gland directly (particularly near the base of the gland), or may ramify in a rather tortuous course in the pial investment of the gland before its terminal branches enter the gland substance. Moreover, cross-connexions may exist, running transversely over the front and back of the gland and joining together the main chorioidal vessels of either side. The further course of the main chorioidal vessels is somewhat unusual, Just above the tip of the pineal gland they may (but do not always) unite to form a single small arteriole which is continued alongside the nervus conarii (i.e. on the lower wall of the vena magna cerebri) and enters the duramater forming the floor of the straight sinus (Text-fig. 6). On its way, it gives off a leash of fine descending arterioles which penetrate the substance of the pineal gland at its apex, and contribute largely to the rich capillary plexus pervading the neuropil core in the macaque epiphysis. In its further course, the main vessel can be followed into the floor of the straight sinus where it breaks up into rather tortuous terminal branches ramifying in a subendothelial position. It is in relation to these branches that the fibres of the nervus conarii so closely run. The intradural course of the artery has been followed in two series of serial sections stained with haemotoxylin and eosin, and in one specimen a small branch (with an accompanying fasciculus of nerve fibres) was found to traverse the lumen of the straight sinus in a trabecular strand of dural tissue.
Text-fig. 5. Drawing of a dissection showing the nervus conarii of a rhesus macaque, extending from the tip of the pineal gland into the dural floor of the straight sinus—viewed from the ventral aspect. A small artery formed by the coalescence of two chorioidal vessels follows the same course. x10. .m.=vena magna cerebri.
Text-fig. 6. The same specimen as that in the previous figure, viewed from the dorsal aspect. The straight sinus has been opened to show the artery ramifying in its floor and lateral walls. x5. P.=pineal gland; v.m.=vena magna cerebri.
In order to enquire whether a similar vascular arrangement might exist in relation to the human pineal gland, two brains were carefully removed at autopsies together with the dura mater wall of the straight sinus. The posterior cerebral arteries were injected with carmine-gelatin through the basilar artery, and the main chorioidal branches were followed by dissection. In neither case, however, were macroscopic arterial twigs traced from any of these branches into the wall of the straight sinus. On the other hand, it was observed that a granular tuft of arachnoidal tissue, similar in appearance to the Pacchionian bodies found in many of the intradural venous sinuses, is present in close relation to the floor of the straight sinus at its commencement.
A complete series of serial sections was prepared from a block removed from a human brain (female, aet. 47) containing the pineal gland and its attachments to the mid-brain and epithalamus, the adjacent part of the cerebellum, the vena magna cerebri, the anterior extremity of the straight sinus, and neighbouring tissues. The block was embedded in celloidin after preliminary treatment with 5 % nitric acid to decalcify any calcareous deposits which might be present in the pineal gland and chorioid plexuses. Sagittal sections were prepared, alternate sections being cut at thicknesses of 30 and 150», and these were stained with haemotoxylin and eosin.
A study of these sections shows a number of points of exceptional interest. The pineal gland itself contains several large calcareous masses (acervuli) with a concentric laminated structure, and also a large cystic cavity of a type which is not uncommonly found here. The nervus conarii is clearly evident and in one of the thick sections its uninterrupted course can be followed up from the tip of the pineal gland along the inferior wall of the vena magna cerebri for a distance of over 6 mm. Its appearance in the adjacent thin section is shown in Textfig. 7 (n.n.). The diameter of the nerve measures 0-1 mm. in section. Within the pineal gland the nerve fibres become dispersed along interlobular septa, and their precise destination cannot be followed. Above the gland the nerve pursues an unbranched course which takes it into the dural wall of the straight sinus, and on its way it passes through a somewhat remarkable formation of the pia-arachnoid. This formation resembles a single large and globular arachnoid granulation, projecting up from the surface of the superior cerebellar vermis. It reaches to, and slightly invaginates, the floor of the junctional region between the vena magna and the straight sinus (Text-fig. 7). At its summit the granulation is adherent to the dural floor of the sinus, but elsewhere it is separated from the dura mater by the subdural space. It measures 4 mm. in height and 2-5 mm. in width at its attached base.
The structure of the granulation is peculiar. Within it is a stroma of unusually dense pial tissue, which forms an interlacing reticulum of well-defined fibrous trabeculae. In the meshes of the latter is a rich plexus of sinusoidal blood-vessels, with several large interconnecting blood sinuses. These cavities are lined by a single-celled layer of endothelium which directly covers the fibrous trabeculae. The large sinuses are disposed mainly in the anterior half of the granulation—where the latter lies in contact with the wall of the great vein of Galen (Text-fig. 7). From this description it will be apparent that in its general appearance the whole structure shows some resemblance to typical erectile tissues. It does not, however, contain any elastic or plain muscle tissue.1
- 1 Some of the spaces seen in this arachnoid structure are evidently subarachnoid spaces containing cerebrospinal fluid, and are to be distinguished from the endothelial-lined blood spaces.
Text-fig. 7. Sagittal section of the pineal gland, vena magna cerebri and adjacent tissues from a human brain. The suprapineal arachnoid body, containing many blood sinuses, is seen projecting up from the surface of the superior cerebellar vermis to abut against the opening of the straight sinus. In adjacent sections the body is seen to be attached directly to the dura mater.
x9. c¢. superior vermis of cerebellum; c.c. space occupied by the splenium of the corpus callosum ; @. great vein of Galen; ”.n. nervus conarii; P. tip of pineal gland; S. commencement of straight sinus; S.P. suprapineal arachnoid body; 7’. tentorium cerebelli.
The functional significance of this vascular arachnoidal granulation can, at the moment, only be tentatively inferred from its anatomical appearance and disposition. In Text-fig. 7 it will be seen that the blood sinuses within the granulation of this particular specimen are partly empty and collapsed. Yet, even in this condition, the structure appears to elevate the floor of the anterior end of the straight sinus and to narrow the opening of the vein of Galen. If it is recognized that the straight sinus is held rigidly in the taut tentorium cerebelli, it seems more than probable that, in a distended state with the sinusoidal cavities filled, the granulation will force up the dural wall of the straight sinus where this forms the lower lip of its opening until it becomes approximated to the upper lip (which here forms rather a sharp angle with the dorsal wall of the vein of Galen). In other words, the granulation seems to provide a ball-valve mechanism which controls the entry of venous blood from the great vein of Galen into the straight sinus. For descriptive convenience the granulation may be termed the “suprapineal arachnoid body”, because of its topographical position above and behind the pineal gland.
Text-fig. 8. Diagram (constructed from serial sections) showing the course of the nervus conarii in the human brain. G. great vein of Galen; J. inferior sagittal sinus; n. nervus conarii; P. pineal gland; S. straight sinus; S.P. suprapineal arachnoid body.
The nervus conarii enters the base of the suprapineal body at a distance of 6-5 mm. from the tip of the pineal gland. It runs a winding course through the body without (so it appears from the sections) giving off any branches, and it actually traverses the cavity of one of the blood sinuses, being ensheathed here with a fine investment of pial tissue. At the summit of the body the nerve runs into the dura mater. Here, after passing through the cavity of a venous lacuna, it turns backwards and courses in a subendothelial position in the floor of the straight sinus (Text-fig. 8). The sections allow it to be followed in this position for 6 mm.; its further course has not yet been followed. The whole length of the nervus conarii, so far as it can be followed in these serial sections, is just 20 mm.
It may be noted that the nervus conarii is accompanied into the dura mater by a minute arteriole (derived from one of the chorioidal vessels), but this is considerably smaller than the nerve. It is therefore quite accessory to the latter. In the whole course of the nerve no evidence was found for the existence of the ‘“‘ganglion conarii” of Pastori.
In silver-impregnated serial sections of the pineal gland and adjacent tissues of another human brain (male, aet. 25), the suprapineal arachnoidal body is particularly obtrusive, for the channels of its sinusoidal plexus are filled with blood. Its relation to the straight sinus and the great vein of Galen, however, are not so clear, since the tissues have become somewhat disorientated in the process of fixation and embedding. Also, the granulation has been sectioned more or less transversely to its long axis. It appears as an ovate body, measuring 2-5 by 1-0 mm., and it can be seen to be insinuated among the dense fibrous strands of the dura mater which form the floor of the straight sinus (PI. II, fig. 4). From the convex surface of the main part of the granulation a small secondary lobule is seen to project. As in the first specimen already described, the pial tissue forming the matrix of the granulation is more dense and less cellular than usual, and it is permeated by a network of irregular blood vessels of a sinusoidal appearance, showing frequent dilatations. In addition, there are to be seen in the granulation a few arterioles of small calibre with a thin muscular wall. The suprapineal body is outlined by a narrow subdural space which, however, is not everywhere distinct. In the dural tissue which immediately surrounds it is a conspicuous bundle of nerve fibres, which is evidently the nervus conarii already described in the previous specimen. In the present case, however, its relation to the pineal gland is not ascertainable since the serial sections do not cover all the field necessary for following its course. This is partly due to the fact that the pineal gland has been considerably distorted by the presence of a large cystic cavity. At one level in the serial sections, however, the nerve can be followed across the subdural space to enter the substance of the suprapineal body. Here it bears a close relation to the sinusoidal plexus, and traverses the cavity of one of the blood sinuses. In sections where the nerve has been cut transversely it is possible to enumerate about 150 nerve fibres in it. Following the nervus conarii section by section through this silverimpregnated material, it was not found to branch, nor did any individual fibres leave the main fasciculus to enter the surrounding tissues either in the suprapineal arachnoid body or in the dura mater in the floor of the straight sinus. In the latter situation (as in the previous specimen) it was seen to traverse the cavity of a venous lacuna.
In the substance of the pineal gland fine nerve plexuses are to be seen on the walls of some of the blood-vessels, but within the too narrow limits covered by the serial sections no continuity could be established between these and the fibres of the nervus conarii within the suprapineal granulation. No dense mass of nerve fibres similar to that observed in the substance of the macaque epiphysis is present in the part of the gland preserved, nor are any nerve cells seen. Also, a careful scrutiny of the sections failed to disclose a “ganglion conarii”.
It has already been noted that, except for the capillary network pervading the central core of neuropil in the rhesus macaque, the pineal gland of this species is not conspicuous for its vascularity. An examination of frozen sections of macaque material, stained by the nitroprusside-benzidene method, was made in order to determine whether the gland is connected with groups of nerve cells in the epithalamus by a vascular mechanism similar to that which has been described by some authorities as existing between the pituitary gland and the hypothalamus. No such vascular connexion appears to exist—indeed the peduncle of the pineal gland contains only a few small capillary vessels.
The observation that in the pineal gland of monkeys there exists a central core of neuropil containing an abundant number of large ganglion cells again raises the question of the relation of this organ to the nervous system. It must be emphasized that this neural component seems to be a pithecoid peculiarity, and the only structure which might be comparable to it in other mammals is the ‘‘ ganglion conarii” as described by Pastori. According to him the ganglion is to be found in the pial tissue close to the tip of the pineal gland in a variety of mammals, including Man. These observations have not been confirmed, however (apart from an isolated observation previously made by Marburg in the brain of a new-born human infant), and in the present study such a ganglion was not found in serial sections of two human pineal glands and adjacent tissues, nor in any of the macaque material. In any case, according to Pastori the ganglion is extremely small, for he states that in Man it consists of about twenty cells only. On the other hand, in the monkey the nerve cells within the pineal gland may amount to over two thousand (Levin, 1938), and they are relatively large and provided with numerous processes. It seems improbable, therefore, that they represent the “ganglion conarii” of other mammals which in this instance has become incorporated within the pineal substance instead of being situated near its apex.
The possible significance of Pastori’s “ganglion conarii” is quite obscure. He describes the cells as giving off two sets of processes—one set proceeding distally to ramify and terminate in the wall of the vena magna cerebri, and the other entering the pineal gland at its tip in company with some small blood vessels. This disposition of the main fibres suggests a vascular reflex mechanism specifically related to the vessels of the pineal gland on the one side and to the great vein of Galen on the other. It remains possible, also, that if the “ganglion conarii” really exists it may be a functional centre for the control of a vascular mechanism such as that which has been described in the present report in the human brain under the name of the suprapineal arachnoid body. It has yet to be shown, however, that a vascular arachnoid granulation of this type exists in relation to the straight sinus in other mammals. Investigations along these lines are now proceeding. In connexion with this discussion it is relevant to note that a few ganglion cells have been observed elsewhere in the pial tissues covering the surface of the brain (S. L. Clark, 1931), while the presence of nerve plexuses in relation to pial vessels generally is well established, the fibres being particularly numerous on the chorioidal arteries.
It has been shown in the present communication that, while the fibres of the nervus conarii extend along the wall of the vena magna cerebri, there is no evidence that they terminate there; on the contrary, they actually run an uninterrupted course to enter the dura mater, and then run backwards, occupying a subendothelial position, in the floor of the straight sinus. In the monkey they are closely related to branches of chorioidal arteries which ramify in the wall of the straight sinus. Itis possible, therefore, that in this animal they may be vasomotor nerves of the ordinary type.
The origin of the fibres of the nervus conarii still remains in doubt. In the macaque monkey they can be traced along small blood-vessels into the central mass of neuropil in the pineal gland, and possibly they arise from the ganglion cells situated here. The general appearance of the nerve and its branchings as these are seen in dissected specimens certainly suggests that the nerve is efferent with respect to the pineal gland. Also, as already remarked by Levin, the fact that a proportion of the fibres leaving the pineal gland in the monkey are rather heavily myelinated suggests that they are unlikely to be postganglionic fibres derived ultimately from cervical sympathetic ganglia. In this connexion it is relevant to note that pial blood-vessels in general may be accompanied by nerve bundles of which some fibres are myelinated, and that nerve fibres have been observed to enter the pia mater directly from cranial and spinal nerve roots (S. L. Clark, 1929, 1981). Further, it has been demonstrated by Chorobski & Penfield (1932) that the perivascular nerve bundles related to cerebral blood-vessels are not appreciably affected by a complete removal of all the sympathetic fibres which accompany the carotid and vertebral arteries into the skull, and also of the greater superficial petrosal nerves. In other words, “‘it is not possible to denervate the cerebral vessels by removing both sympathetic and parasympathetic innervation”.1
- 1 It is certain that by omitting to take into account this important fact some physiologists have been led in the past to underestimate the efficacy of the vasomotor control of the cerebral arteries.
From the central mass of neuropil in the macaque pineal gland, strands of fibres can also be traced to the more proximal part of the gland in relation to blood-vessels, and here they intermingle with bundles of nerve fibres which enter the lateral aspect of the gland with branches of the chorioidal arteries. At the base of the epiphysis these plexiform fibres come into relation and freely intermingle with fibres from the habenular and posterior commissures which can be seen entering the pineal stalk. It is this intermingling which makes so difficult or impossible the tracing in serial sections of fibres from the commissures. There has never been any doubt that the pineal gland contains nerve fibres derived from perivascular plexuses accompanying chorioidal vessels, and these have commonly been regarded as derivatives of the sympathetic nerves accompanying the carotid and vertebral arteries. On the other hand, there has been considerable divergence of opinion regarding the contribution of the habenular and posterior commissures to intrapineal plexuses. In the present study it has been established that at least a proportion of these commissural fibres enter the gland on one side of the peduncle, only to leave it by the other side and rejoin the commissures. Moreover, the component fibres of these aberrant fasciculi may become splayed apart and then run a tortuous course among the parenchymatous cells of the pineal gland, so that the fasciculi give an appearance in single sections of breaking up into a spray of terminal fibres. It is not possible, of course, to affirm that all the commissural fibres which enter the pineal parenchyma behave in this way, but these observations allow a fair presumption that this may be the case.
The unusual course of the chorioidal vessels related to the pineal gland of the rhesus macaque, whereby they extend actually into the wall of the straight sinus and there break up into terminal ramifications, is evidently associated functionally with the nervus conarii, for the fibres of the latter run in close relation with their branches. In the human brain no macroscopically visible branches of the chorioidal arteries have such an intradural extension. On the other hand, a microscopic arteriole follows the nervus conarii of Man into the floor of the straight sinus, and a fine plexus of blood-vessels can also be followed up in the tunica adventitia of the vena magna cerebri.
The existence, in relation to the opening of the great vein of Galen into the straight sinus, of an arachnoidal formation filled with blood sinusoids, and with an intrinsic structure recalling that of erectile tissue, is an observation which has not apparently been made before in the human brain}. It has been pointed out that this peculiar formation (here termed the suprapineal arachnoid body) possibly constitutes a neurovascular mechanism whereby the venous return through the great vein of Galen is regulated. The pial vessels in the neighbourhood of the suprapineal body are innervated by abundant nerve fibres, and the latter could supply the means whereby the filling of the blood sinuses is controlled. It has been shown that the nervus conarii in its course to the floor of the straight sinus traverses the cavity of one of the blood sinuses within the suprapineal body, but the material has shown no evidence that any of the fibres of this nerve end here. It may be noted that when the brain is removed in the ordinary way from the intracranial cavity the suprapineal arachnoid body will be torn through at its attachment to the dura mater of the tentorium cerebelli; consequently its real nature will escape detection in such material. Those who are accustomed to the examination of human brains in anatomical or pathological departments, however, will be familiar with the small patch of dense and opaque pia-arachnoid tissue which is always to be seen on the superior vermis of the cerebellum where this lies in relation to the anterior end of the straight sinus. This patch marks the position of the suprapineal arachnoid body, and there are frequently found in relation to it a few small arachnoid granulations of the usual type.
- 1 This structure has been observed histologically in four specimens. It is perhaps hardly necessary to say that its constancy can only be determined by the examination of many more brains.
In the monkey a suprapineal body comparable to that of the human brain has not been identified. On the other hand, recurrent twigs from the artery accompanying the nervus conarii form a rich plexus in the pial tissue on the ventral surface of the great vein of Galen, and it is possible that these form part of a neurovascular mechanism which may play a role similar to that suggested for the suprapineal body. In this connexion it may be recalled that among the vessels in this pial tissue some sections show a globular skein of nerve fibres resembling a sensory nerve ending. It is also possible that the terminal branches of the chorioidal artery, which ramify in a curiously tortuous manner in the wall of the anterior end of the straight sinus (and which are accompanied by fibres of the nervus conarii), may be related to a reflex mechanism concerned with the venous return through the vein of Galen. These are problems which now require investigation.
- The pineal gland of the rhesus macaque contains a central core of neuropil in which are embedded numerous large ganglion cells with branching processes.
- Contributing to this network of nerve fibres are perivascular plexuses accompanying branches of the chorioidal arteries which penetrate the pineal gland from its lateral aspect, and also a conspicuous fasciculus which can be traced to the apex of the pineal gland where it emerges as the nervus conarii.
- Fibres from the habenular and posterior commissures enter the substance of the pineal gland through its peduncle, but on tracing these through serial sections many are found to be merely aberrant commissural fibres which enter the peduncle on one side and leave it on the other. It is considered not improbable that all the fibres from the commissures which have been followed into the parenchyma of the pineal gland may be of a similar nature.
- Some of the fibres of the posterior commissure certainly terminate in relation to the ependymal epithelium lining the posterior wall of the pineal recess, and here show regular beading and minute end-bulbs.
- The central core of neuropil in the macaque epiphysis is pervaded by a rich capillary plexus. Elsewhere the gland shows no great vascularity.
- No system of blood-vessels is present which links the pineal gland with cell collections in the epithalamus comparable to that which has been described in relation to the hypophysis and the hypothalamus.
- In the monkey a chorioidal vessel extends up into the wall of the straight sinus, where it ramifies in a sub-endothelial position. From this vessel recurrent twigs descend to enter the pineal gland at its apex.
- The nervus conarii in the monkey has been traced from the central core of neuropil in the pineal gland into the wall of the straight sinus. Here it ramifies in a plexiform manner in a sub-endothelial position, its fasciculi usually bearing a close topographical relation to branches of the chorioidal artery which are also found here.
- Some sections show a globular skein of nerve fibres in the pial tissue between the pineal gland and the straight sinus, resembling a sensory nerve ending.
- In the human pineal] gland the nervus conarii has been recognized. It emerges from the tip of the gland and runs an uninterrupted and apparently unbranched course to reach the dura mater of the tentorium cerebelli. Here it runs back in the floor of the straight sinus occupying a subendothelial position. The nerve has been followed in serial sections for a distance of 20 mm. Its destination (in a peripheral direction) has not been determined.
- A formation of the arachnoid has been described in relation to the floor of the straight sinus where the great vein of Galen opens into it. This structure somewhat resembles a large arachnoid granulation of the usual type, but its stroma consists of dense pial tissue containing a sinusoidal plexus of blood vessels and several large blood sinuses. It has been termed the suprapineal arachnoid body.
- From its structure and disposition it is suggested that the suprapineal body may provide a ball-valve mechanism whereby the venous return from the great vein of Galen is regulated and controlled.
- On its way to the dural floor of the straight sinus the nervus conarii in the human brain was found in two specimens to pass through the suprapineal body and traverse one of the blood sinuses therein.
- No evidence was found, either in macaque or human material, for the existence of the “‘ganglion conarii” as described by Pastori.
I wish to acknowledge the valuable assistance of my technician, Mr E. A. Thompson, in the preparation of the histological material and particularly in completing the beautiful series of sections through the human pineal gland and adjacent tissues of which Text-fig. 7 represents one section. I would also thank Mr W. Chesterman for the examples of his skill in photomicrography.
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EXPLANATION OF PLATES I AND II
Fig. 1. Sagittal section of the tip of the pineal gland of a rhesus macaque, stained by Bodian’s protargol technique. The nervus conarii is seen emerging from the gland and passing along the ventral wall of the vena magna cerebri. x 118. Fig. 2. Section of the pineal gland of the rhesus macaque, showing the central core of neuropil and nerve-cells. Stained by Bodian’s protargol method. x 160.
Fig. 3. Section of the pineal gland of the rhesus macaque, showing two ganglion cells. Stained by Bodian’s protargol method. x 500.
Fig. 4. Section through the suprapineal arachnoid body of a human brain, stained by Bodian’s protargol method. The body is filled with sinusoidal blood-vessels containing blood corpuscles. In the dura mater surrounding the body is seen the nervus conarii, cut in two portions (n.n.). Above is seen a lobule of the suprapineal body which in this section has the appearance of being detached from the main part. GNVIS IVANId AAT—MUVIO SOUD AT
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