The vascularization of the developing CNS begins at the myelencephalon and ascends progressively through the metencephalon, mesencephalon, diencephalon, striatum and telencephalon (cerebral cortex) which is the last region to be vascularized (Streeter 1918, Bar and Wolff 1972, Marin-Padilla 1985b). Therefore, it follows an ascending sequential gradient which keep pace with the CNS ascending differentiation and maturation. By the 7th gestational week of human development early vascularization of the medulla (Fig 2.2A), the pons (Fig 2.2B), the diencephalon, and the striatum (Fig 2.2C) is already underway. However, the cerebral cortex (Fig 2.2D) still lacks its intrinsic vasculature. The human cerebral cortex does not start to vascularize until around the 8th week of embryonic age. Its vascularization follows a ventro-lateral-medial sequential gradient which is synchronous with its advancing differentiation and maturation.
The cephalic region of the developing CNS is surrounded by the embryonic meninges. They constitute a prominent and quite large tissue compartment (Fig 2.2). The embryonic meninges are well vascularized before the vascularization of the CNS begins (Figs 2.2, 2.3). Three distinct primordial lamellae: the dura, the arachnoid and the pia mater are recognizable (Fig 2.3). However, there are no distinct separations or tissue spaces between them. The blood vessels of the embryonic meninges can also be separated into three distinct strata (Figs 2.2, 2.3). The outer stratum (Fig 2.3) carries the dural vessels from which the venous sinuses of the CNS evolve. The intermediate stratum, which is the largest, carries the arachnoidal vessels from which the main arterial and venous systems of the CNS evolve. The inner stratum carries the pial vessels from which the pial vascular plexus evolves. The embryonic pial plexus covers the entire surface of the developing CNS, and adapts intimately to its variable external morphology (Figs 2.2, 2.3). Its formation always precedes the intrinsic vascularization of any of the CNS regions (Fig 2.2). All perforating vessels which enter into the various regions of the developing CNS originate from their overlying pial vascular plexus. All meningeal vessels, including the dural, the arachnoidal and the pial vessels, constitute together the perineural vascular territory of the CNS vasculature.
Fig 2.1 Reconstruction of the cephalic vascular plexus of a 21 mm human embryo of about 50 days illustrating the organization and distribution of its embryonic vessels. Many of the main arteries, veins and venous sinuses which characterize the adult brain can already be recognized. All vessels illustrated are components of the perineural vascular territory of the CNS vasculature. However, the pial vascular plexus is not illustrated. A portion of the cerebral cortex has been removed to demonstrate the vascularization of its choroid plexus, the anterior cerebral artery and the sinus rectus. The thin embryonic cerebral cortex still has no intrinsic vasculature at this age. (From Streeter, G. L: Contr. Embryol. Carneg. Instn 8: 5, 1918.)
The subsequent development of the head vascular plexus (Fig 2.1) is complex because it actually comprises the concomitant formation of three different but interrelated vascular systems, dural, arachnoidal and pial – strata. The sequential embryonic development of the main arteries, veins and venous sinuses of the perineural vascular territory of the brain has been studied in great detail by several investigators (Streeter 1918, Padget 1948, 1957, Bär and Wolff 1972, Wolff et al. 1975). These studies represent the most complete account of the vasculogenesis of any region of the developing CNS.
Figs 2.4 and 2.5 are reproduced from the original works of Padget (1948, 1957). In these diagrams the complete prenatal development of each of the main vessels of the brain can be analyzed and followed in detail. It should be emphasized that the illustrations (Figs 2.4, 2.5) only represent the prenatal development of the main arterial and venous systems of the brain. They do not supply information regarding the development of the arachnoidal connecting vessels nor of the pial vascular plexus, which are also important components of the perineural vascular territory of the CNS vasculature.
Fig 2.2 Composite figure illustrating a parasagittal section (1) of the head of a 50 day human embryo, and a coronal section (2) of the anlage of the cortical choroid plexuses from a younger, 43 day old, human embryo. The parasagittal section illustrates the major regions of the developing brain, the abundant and well vascularized arachnoidal tissue (a), and the pial vascular plexus (p). The lateral (LV), third (III), and fourth (IV) ventricles; and, aqueduct of Sylvius (S) identify the embryonic cerebral cortex, the diencephalon, the cerebellar primordium and the mesencephalon, respectively. The intrinsic vascularization of the medulla (A), the pons (B) and the striatum (C) is already underway while that of the cerebral cortex (D) has not yet started. The abundant arachnoidal tissue (a) and the pial vascular plexus (p) are also illustrated in these four CNS regions. The coronal section illustrates the dural (d), the arachnoidal (a) and the pial (p) vessels around the still unvascularized embryonic cerebral cortex (cc). The cortical pial vascular plexus (p) extends into the anlage of the choroid plexuses (cp) establishing its tela choroidea from which its vascularization will evolve. (From Hamby, W. B.: J. Neurosurg. 15: 65–75, 1958.) H&E preparations, parasagittal section, x20.
Fig 2.3 Camera lucida drawings of the embryonic meninges covering the cerebral cortex of a 50 day human embryo, illustrating its composition and structural organization. Three primordial lamellae are recognized in it. The outer or dural lamella (D) is composed of closely arranged elongated cells which congregate below the developing membranous neurocranium. The intermediate or arachnoidal lamella (A) is composed of loosely arranged stellate cells with long fine cytoplasmic processes with apparently empty spaces between them. The inner or pial lamella (P) has fewer cells and more vessels than the other two and is in contact with the surface of the cerebral cortex. The surface of the cerebral cortex is composed of the closely apposed endfeet (G) of the marginal glia covered by the CNS external basal lamina. Some meningeal vessels have attachments of non-endothelial cells (arrows), which might represent precursors of pericytes and smooth muscle cells, and have circulating blood cells in their lumina. The thickness of the cortical meninges illustrated is approximately 100 micrometers. (Compare with Fig 2.13.)
The perineural vasculature undergoes an integrative development continuously adapting to the changing external morphology of the growing brain. The extraordinary development of the human cerebral cortex represents perhaps the most significant single factor underlying the remarkable developmental metamorphosis of the intracranial vasculature (Figs 2.4, 2.5). The cerebral cortex evolves from a small vesicle at the anterior end of the brain (Fig 2.2) to a large structure which comes to occupy practically the entire cranial cavity (Figs 2.4, 2.5). The adaptative metamorphosis of arteries and veins to the expanding cerebral cortex are clearly demonstrated in the accompanying illustrations (Figs 2.4, 2.5). It is quite obvious from these illustrations that in the course of embryonic development the location and distribution of the different blood vessels change continuously. This adaptative vascular metamorphosis is the result of continuous and concomitant capillary angiogenesis and capillary reabsorption. The original anastomotic plexus formed by the perineural vessels undergoes continuous remodelling by the addition of new links (angiogenesis) around growing or expanding regions and by the elimination of others (reabsorption) when no longer needed. Undoubtedly, the loose structural organization of the embryonic arachnoidal mesh and its abundance (Figs 2.2, 2.3) provide an ideal tissue substratum for these vascular adaptations. In