Neural - Ventricular System Development

Introduction

The ventricular system develops from the single cavity formed from the hollow neural tube. This fluid-filled space is separated from the amnion following fusion of the neural tube and closure of neuropores. At different regions sites within the wall (floor of lateral ventricle and roof of the third and fourth ventricles) differentiate to form choroid plexus a modified vascular structure which will produce Cerebrospinal fluid (CSF)

In development and the space within the spinal cord (central canal) and the brain (ventricles) was derived from the same space within the neural tube. In the adult these 2 spaces remain connected containing the same CSF.

Early in development the cavity within the neural tube (which will form the ventricular space) is filled with amniotic fluid. As the brain and spinal cord grow, this fluid filled space makes up the majority of the nervous system (by volume). Upon closure of the neuropores and development of the embryonic vasculature, this fluid is then synthesized by the choroid plexus, a specialized vascular epithelium. In mammals, the choroid plexuses develop at four sites in the roof of the neural tube shortly after its closure, in the order forth (IV, lateral, and third (III) ventricles.

The choroid plexuses form one region of the blood-brain barrier that regulates the brain's internal environment.

Normal CSF contains high amounts of salts, sugars and lipids and low amounts of protein (0.3-0.7 microg/microL), though there appears to be 60+ proteins as identified by 2D gel. Presence of some protein in the CSF can be indicative of disruption of or incomplete blood/brain barrier.

Development Overview

Ventricles and Central Canal

Stage 11 - appearance of the optic ventricle. The neural groove/tube space is initially filled with amniotic fluid.

Stage 12 - closure of the caudal neuropore, onset of the ventricular system and separates the ependymal from the amniotic fluid

Stage 13 - cavity of the telencephalon medium is visible

Stage 14 - cerebral hemispheres and lateral ventricles begin, rhomboid fossa becomes apparent.

Stage 15 - medial and lateral ventricular eminences cause indentations in the lateral ventricle

Stage 16 - hypothalamic sulcus is evident

Stages 17-18 - interventricular foramina are becoming relatively smaller, and cellular accumulations indicate the future choroid villi of the fourth and lateral ventricles

Stage 18 - areae membranaceae rostralis and caudalis are visible in the roof of the fourth ventricle, and the paraphysis is appearing.

Stage 19 - choroid villi are visible in the fourth ventricle, and a mesencephalic evagination (blindsack) is visible

Stage 20 - choroid villi are visible in the lateral ventricle

Stage 21 - olfactory ventricle is visible

Stages 21-23 - lateral ventricle has become C-shaped (anterior and inferior horns visible). Recesses develop in the third ventricle (optic, infundibular, pineal).

Fetal Period - posterior horn of the lateral ventricle, choroid plexus of the third ventricle, suprapineal recess, interthalamic adhesion, aqueduct, and apertures in the roof of the fourth ventricle.

(Data from: O'Rahilly R, Müller F., 1990)

Choroid Plexus Development

Epithelium from the neural tube epithelium.

Mesenchyma from the meninges.

Enzymes required for CSF production are Na+/K+ ATPase and carbonic anhydrase.

Subarachnoid Space Development

Stage 14 (33 days) - initially as irregular spaces on the ventral surface of the spinal cord.

Stage 18 (44 days) - dura mater is formed and spaces surround the circumference of the spinal cord, which coalesce and contain many blood vessels.

(Data from: Patelska-Banaszewska M, Wozniak W., 2005)

CSF Synthesis

Two key enzymes are required to produce CSF they are the Na+/K+ ATPase and carbonic anhydrase.

Other known chorid plexus enzymes include: alkaline and acid phosphatases, magnesium-dependent ATPase, glucose-6-phosphatase, thiamine pyrophosphatase, adenylate cyclase, oxidoreductase, esterases, hydrolases, cathepsin D, and glutathion S-transferase. (More? Catala M., 1998)

"The epithelial cells of the choroid plexus secrete cerebrospinal fluid (CSF), by a process that involves the movement of Na(+), Cl(-) and HCO(3)(-) from the blood to the ventricles of the brain. This creates the osmotic gradient, which drives the secretion of H(2)O. The unidirectional movement of the ions is achieved due to the polarity of the epithelium, i.e., the ion transport proteins in the blood-facing (basolateral) are different to those in the ventricular (apical) membranes."

(text from: Speake T, Whitwell C, Kajita H, Majid A, Brown PD. Mechanisms of CSF secretion by the choroid plexus. Microsc Res Tech. 2001 Jan 1;52(1):49-59. Review.)

CSF Reabsorption

Arachnoid Granulation (image: Gray's Anatomy)

CSF drainage (absorption or reabsorption) into the venous system is through arachnoid granulations.

CSF in the subarachnoid space extends into the arachnoid granulations, which then project through the dura into the superior sagittal sinus.

See also note in CSF Circulation section, point 3.

Adult CSF Normal Values

(Lumbar CSF)

Opening pressure: 50–200 mm H2O CSF

Color: Colorless

Turbidity: Crystal clear

Mononuclear cells: less than 5 / mm3

Polymorphonuclear leukocytes: 0

Total protein: 22–38 mg/dl Range 9–58 mg/dl (mean ± 2.0 SD)

Glucose: 60–80% of blood glucose

(Data from: Clinical Methods, 3rd ed, Table 74.1)

CSF Circulation

Greitz D. Cerebrospinal fluid circulation and associated intracranial dynamics. A radiologic investigation using MR imaging and radionuclide cisternography. Acta Radiol Suppl. 1993;386:1-23. (modified text below from this reference abstract)

1. CSF-circulation is propelled by a pulsating flow, which causes an effective mixing. Flow is produced by the alternating pressure gradient, which is a consequence of the systolic expansion of the intracranial arteries causing expulsion of CSF into the compliant and contractable spinal subarachnoid space.
2. No bulk flow is necessary to explain the transport of tracers in the subarachnoid space.
3. Main absorption of the CSF is not through the Pacchionian granulations (arachnoid granulations), but a major part of the CSF transportation to the blood-stream is likely to occur via the paravascular and extracellular spaces of the central nervous system. (MH- Note this statement conflicts with previous CSF Reabsorption in literature)
4. The intracranial dynamics may be regarded as the result of an interplay between the demands for space by the four components of the intracranial content (arterial blood, brain volume, venous blood and CSF). # # Interaction has a time offset within the cerebral hemispheres in a fronto-occipital direction during the cardiac cycle (the fronto-occipital "volume wave").
5. Outflow from the cranial cavity to the cervical subarachnoid space (SAS) is dependent in size and timing on the intracranial arterial expansion during systole.