Fig 2.4 Series of diagrams illustrating the prenatal developmental metamorphosis of the major arterial systems of the human brain. The illustrations are self explanatory. (From Padget, D. H.: Contr. Embryol. Carneg. Instn 32: 207, 1948.)
Fig 2.5 Series of diagrams illustrating the prenatal developmental metamorphosis of the major venous systems and sinuses of the human brain. The illustrations are self explanatory. (From Padget, D. H.: Contr. Embryol. Carneg Instn 34–79, 1957.)
In the course of embryonic development, the arachnoidal mesh is traversed by numerous vessels of various calibers linking the main arteries and veins with the pial vascular plexus (Figs 2.2, 2.3). The size, number, location and distribution of the connecting arachnoidal vessels also undergo continuous developmental modifications and rearrangements by both capillary angiogenesis and reabsorption. Early in development, these vessels are large, irregular, thin walled, and composed of several endothelial cells joined by tight junctions (Fig 2.3). There are no recognizable arteries or veins and all of them appear to be growing actively by sprouting. Later in development, the arachnoidal arteries and veins become surrounded by arachnoidal cells which isolate them from the cerebrospinal fluid (CSF) compartment. The adult arachnoidal vessels thus become enclosed within distinct perivascular tissue spaces which seem to be analogous and continuous with those of other vessels of the body (see Fig 2.13). Furthermore, according to recent observations (Casley-Smith et al. 1976, Krisch and Buchheim 1984, Pile-Spellman et al. 1984) the perivascular spaces of the adult arachnoidal vessels seem to drain independently through the lymphatic system.
The simple structural organization of the embryonic meninges is also progressively transformed to accommodate the vascular modifications (Table 2.1, see Fig 2.13). The three original lamellae of the embryonic meninges become eventually duplicated and distinct tissue spaces are formed between them (Table 2.1). The progressive establishment of different meningeal tissue spaces and their association to its vessels are indicative of the acquisition of important functional roles, some of which are not yet clearly understood. The possible functional roles of these meningeal spaces, their relationships to the perivascular spaces, to the cerebrospinal fluid (CSF) compartments, and to the CSF circulation have recently received the attention of several investigators (Andres 1967a,b, Morse and Low 1972, Nabeshina et al. 1975, Oda and Nakanishi 1984, Krisch et al. 1983, 1984). However, the embryonic timing for the establishment of the various meningeal compartments and their association to the development of the perivascular tissue spaces need to be more accurately determined.
Although, the pial vascular plexus is a component of the perineural vascular territory of the CNS vasculature, its embryonic development, composition, structural organization, and functional role will be best appreciated in conjunction with the development of the interneural vascular territory.
Interneural Vascular Territory of the CNS Vasculature
Of the three vascular strata (the dural, the arachnoidal and the pial) which constitute the perineural vascular territory of the CNS vasculature, the pial vessels play the most important role in its early intrinsic vascularization. While the main arterial and venous system of the CNS, together with the arachnoidal connecting vessels, may be considered mere conductors for the blood, the pial vessels participate directly in the intrinsic vascularization of all regions of the CNS and of the choroid plexuses.
The pial vascular plexus is recognized throughout the entire surface of the embryonic CNS. Its formation always precedes the intrinsic vascularization of any of its regions. At 50 days gestation, the human cerebral cortex, although lacking its own vasculature, is already surrounded by a prominent pial vascular plexus (Figs 2.2, 2.3). This pial plexus will provide all the vessels which perforate through the surface of the developing cortex as well as those of the tela choroidea from which the vascularization of its choroid plexuses evolves (Fig 2.2).
Three early developmental aspects of the cortical pial vascular plexus will be reviewed in detail. Its embryonic composition and structural organization will be analyzed first. The vascular perforation of the cortical surface by the pial vessels will be analyzed next, to illustrate its sequential nature. Finally, the formation of the embryonic Virchow-Robin compartment (VRC) around the perforating vessel will be analyzed. The perforating vessels within the VRC constitute the interneural vascular territory of the CNS vasculature.
Composition and Organization of the Pial Vascular Plexus
The pial vascular plexus is supplied by connecting arachnoidal vessels which link the main arteries and veins with it (Figs 2.2, 2.3). It is composed of vessels of variable caliber, ranging from small ones lined by a single endothelial cell to larger ones lined by several endothelial cells joined by tight junctions (Figs 2.6, 2.7, arrows). They constitute a extensive short-link anastomotic plexus over the entire surface of the developing cortex. The pial plexus continuously expands and adapts to the changing external morphology of the CNS surface by capillary angiogenesis and reabsorption.
The pial vessels are separated from each other by the cytoplasmic processes of pial cells, by fine collagen fibers, and by tissue spaces (Figs 2.6, 2.7, 2.9). The primitive pial cells are elongated elements lacking distinctive features. They are frequently associated with fine collagen fibers and some contain vacuoles in their cytoplasm (Figs 2.6, 2.7). Embryonic pial cells are specific meningeal elements (Andres 1967a,b, Krisch et al. 1983, 1984). They share features of fibroblasts (collagen formation), of mesodermal cells (phagocytosis), and of epithelial cells (formation of epithelial-like lamellae).
Pial vessels have a distinct but thin basal lamina which is lacking in zones of active angiogenesis. The leading endothelial cells of its growing vessels have characteristic features. They show considerable membrane activity with the formation of pseudopodia and fine filopodia which project both inside and outside of their lumina (Figs 2.6, 2.7, 2.9). They are also characterized by a prominent and abundant granular endoplasmic reticulum filled with dense and fine granular material (Figs 2.6, 2.7, 2.9). The accumulation of this dense material often causes dilation of the endoplasmic reticulum. Although, the nature of this dense material remains unknown, its association with the advancing endothelial cells of growing capillaries suggests two possibilities. First, it could represent proteinaceous secretion for the formation of the basal lamina of the newly formed vessel, second, this material could be used in the formation of the first lumina (canalization) between the advancing endothelial cells of a growing vessel (Manasek 1971). Further investigation will be necessary to elucidate the nature of this proteinaceous material and its possible role in embryonic angiogenesis.
The surface of the embryonic cerebral cortex is composed of the closely apposed glial endfeet of the marginal glia covered by CNS external basal lamina (Figs 2.6, 2.9). The CNS external basal lamina, together with the marginal glia constitute a distinct anatomical barrier which must be perforated by the pial vessels in order to penetrate the nervous tissue.
Vascular Perforation of the CNS Surface by Pial Vessels
Recent electron microscopic studies (Marin-Padilla 1985a,b) of the early vascularization of the embryonic cerebral cortex have demonstrated the sequential nature of the vascular perforation of the CNS surface by pial vessels. Three fundamental stages