2.9 Schematic drawings illustrating the three fundamental stages of the vascular perforation of the surface of the embryonic cerebral cortex (G) by pial vessels (P). The following stages (from left to right) are illustrated: a) the early endothelial filopodia perforations; b) the endothelial cell perforation and proliferation with the in situ formation of a new intracortical vessel; and c) the establishment of the Virchow-Robin compartment (VRC). The fusion of the vascular and CNS external basal laminae around the perforating vessel and its participation in the formation of both the pial-funnel and the embryonic Virchow-Robin are also illustrated. The composition and organization of the embryonic VRC viewed in longitudinal and transverse (thick arrow) perspectives are also illustrated. The embryonic VRC represents a perivascular tissue space (ICS) formed between the vascular and the CNS basal laminae (BL). It contains the perforating vessel (E) with paravascular cells (P) enclosed within its basal lamina (curved arrows), the cytoplasmic processes of pial cells, and fine collagen fibers. The vessels within the VRCs constitute the interneural vascular territory of the CNS vasculature. At various depths into the nervous tissue the VRC closes off with the fusion of the vascular and the CNS basal laminae into a single layer which surrounds and accompanies the penetrating vessels into the CNS substance. Only capillaries arriving from the vessels of the VRC actually penetrate into the nervous tissue proper. They grow actively establishing short-link anastomotic plexuses throughout the nervous tissue. They constitute the intraneural vascular territory of the CNS vasculature. The three insert drawings (A, B, C) illustrate the type of progressive vascularization observed in the developing cerebral cortex. New pial vessels perforate the cortex between previous perforation sites, thus progressively vascularizing the expanding cerebral cortex. The ependymal cell layer (E) with its multiple mitoses is also illustrated. The composition and structural organization of both the embryonic and the adult VRC (compare with Fig 2.10) are essentially indentical.
In Situ Formation of New Intraneural Vessels
The original opening between the fused vascular and CNS basal laminae gradually enlarges, thus allowing endothelial cells to penetrate the nervous tissue (Figs 2.8, 2.9). The subsequent proliferation of the penetrating endothelial cells results in the formation in situ of a new intraneural vessel (Fig 2.8, insert). As the newly formed intraneural vessel advances into the nervous tissue, the original pial-funnel elongates downward and accompanies the vessel for a short distance (Fig 2.9). The glial endfeet under the perforating endothelial cells undergo swelling, membrane disintegration and myelin figures are often recognized in the area (Fig 2.9). As the newly formed vessel advances into the nervous tissue new glial processes start to surround it (Fig 2.8). These new perivascular glial processes become continuous with the marginal glia of the CNS surface, and are subsequently covered by basal lamina material (Figs 2.8, 2.9). Therefore, the perforating vessel becomes progressively separated from the nervous tissue by a new glial wall which is continuous with the CNS surface (Fig 2.9). Furthermore, the embryonic structure of the new glial, wall formed around the perforating vessel, is similar to that of the CNS surface. The proximal portion (near the CNS surface) of the perforating vessel is thus kept outside of and “in between” the nervous tissue proper, and hence, within the embryonic VRC. However, the leading endothelial cells of perforating vessels continue to advance freely, without recognizable basal lamina, into the developing nervous tissue (Fig 2.9).
Different stages of vascular perforations are recognized during early development in all regions of the CNS. In the cerebral cortex, new vascular perforations occur during its entire prenatal development. As the cortex expands, new perforations occur between previous ones, following a sequence which is schematically illustrated in Fig 2.9 (A,B,C, inserts). The formation of the embryonic pial-funnel and its role in the establishment of the embryonic VRC are also illustrated (Fig 2.9).
Finally, it is important to emphasize that pial vessels always perforate the external basal lamina and marginal glia of the CNS surface to enter the nervous tissue, but do not perforate them to exit. Therefore, it would seem that in the course of embryonic development the direction of the blood flow eventually determines which vessels will be transformed into entering arterioles, and which into existing venules.
Establishment of the VRC and Interneural Vascular Territory
The early pial-funnel established around the entrance of the perforating vessel, by the fusion of both basal laminae, undergoes significant modifications in the course of embryonic development (Figs 2.8, 2.9). Between the two fused basal laminae a shallow space is formed which communicates with the tissue spaces of the pia mater. This space elongates downward and accompanies the perforating vessel, for a short distance, into the nervous tissue. It is subsequently invaded by pial cellular elements, fine collagen fibers, and non-endothelial paravascular cellular elements (Figs 2.8, 2.9, arrows). Thus, the original pial-funnel is progressively transformed into a distinct perivascular compartment known as the VRC (Figs 2.8, 2.9). The embryonic VRC becomes progressively walled by new glial processes which are arranged in a manner structurally similar to that of the marginal glia of the CNS surface. Therefore, its vessels remain outside of “in between” the nervous tissue proper (Fig 2.9). The embryonic composition and structural organization of the VRC does not significantly change in the course of embryonic development (Fig 2.10). Both, the embryonic and the adult VRC (Jones 1970) have similar composition and overall organization (compare Figs 2.8 and 2.10). However, the early communication of the embryonic VCR with the pial space is eventually obliterated, as recently pointed out by some investigators (Krisch et al. 1983).
As the VRC becomes disconnected from the pial space it is transformed into a specific perivascular compartment entirely outside of the nervous tissue proper. The VRC (Figs 2.9, 2.10) is established between the vessel wall and the glial wall of the nervous tissue. Its embryonic vessels are transformed into arterioles and venules which can reach to considerable depths within the nervous tissue, without penetrating the neural parenchyma (Duvernoy et al. 1981). Although the VRC of the cerebral cortex could reach down as far as the white matter, its vessels remain outside and walled between the nervous tissue (Jones 1970). Therefore, the VRC vessels constitute an important and specific vascular territory of the CNS vasculature. This interneural vascular territory must be distinguished from the perineural and the intraneural territories. The perivascular spaces around the VRC vessels are anatomically independent from the meningeal compartments and from the perivascular glia compartment of the perineural and intraneural vascular territories, respectively. The drainage of the VRC is also independent from the meningeal compartments. It seems to be connected with the perivascular tissue spaces of the arachnoidal vasculature, and hence with the lymphatic system (Krisch and Buchheim 1984, Pile-Spellman et al. 1984). The early development of these anatomical differences undoubtedly results in the acquisition of different and specific functional roles for each of three vascular territories which characterizes the CNS vasculature. The establishment (embryonic timing) and the nature of these different functional roles have not been adequately studied.
Fig 2.10 Ultrastructural composition and organization of a fully developed Virchow-Robin compartment from the cerebral cortex of an adult cat. Its perivascular tissue space (PS) is clearly visible between the vascular and the CNS basal laminae (BM). This space contains the cytoplasmic processes of leptomeningeal (pial) cells (arrows), collagen fibers and the perforating vessels with perivascular pericytes and/or smooth muscle cells (S) enclosed within their basal laminae. Therefore, the basic composition and structural organization of the Virchow-Robin compartment remain practically unchanged in the course of embryonic development (compare with Fig 2.9). (From Jones, E. G.: J. Anat. [Lond.] 106: 507, 1970), x17000; insert) x2500.
In the course of embryonic development, as the original pial perforating vessels enlarge they become more directly
