Morphology and molecular properties of cellular components of normal cerebral vessels.

Abstract

The blood-brain barrier (BBB) includes anatomical, physicochemical, and biochemical mechanisms that control the exchange of materials between blood and brain and cerebrospinal fluid (CSF). Thus two distinct systems, the BBB and the blood-CSF barrier systems, control cerebral homeostasis. However, both systems are unique, the BBB having a 5000-fold greater surface area than the blood-CSF barrier (,). The concentrations of substances in brain interstitium, which is determined by transport through the BBB, can differ markedly from concentrations in CSF, the composition of which is determined by secretory processes in the choroid plexus epithelia (). This review will focus on cellular components of cerebral vessels with emphasis on endothelium, basement membrane, and pericytes as well as the perivascular macrophage (Figs. 1 and 2 A), which in light of new information is distinct from pericytes. This review deals less with pathogenesis and more with some of the molecules that have been discovered in these cell types in the past decade. Although astrocytes invest 99% of the brain surface of the capillary basement membrane and are important in induction and maintenance of the BBB, this topic will not be discussed and readers are referred to reviews in the literature (, , , , , , , ). Open image in new window Fig. 1. Segment of normal cerebral cortical capillary wall consists of endothelium (e) and a pericyte (p) separated by basement membrane. This rat was injected with ionic lanthanum, which has penetrated the interendothelial space upto the tight junction (arrowhead). ×70,000. Open image in new window Fig. 2. (see facing page) (A) A cryostat section shows perivascular macrophages using anti-ED2 antibody. The inset shows these cells at higher magnification. Note that these cells are associated with vessels, which have the caliber of veins and not capillaries. (C,D) Merged confocal images of normal rat brain dual labeled for Ang-1 and Ang-2 proteins. Normal vessels show endothelial localization of Ang-1 (green) only in rat brain (B) and choroid plexuses (C) and there is no detectable localization of Ang-2. Note the granular immunostaining in choroid plexus epithelial cells indicating colocalization of Ang-1 and Ang-2 (yellow). (D) Cultured cells derived from cerebral microvessels show adherance of antibody-coated ox red blood cells forming rosettes indicating presence of Fc receptors. Note that many of these cells contain Factor VIII indicating that they are endothelial cells (arrowheads). (E) Electron micrograph demonstrating that the cells to which antibody-coated ox red cells have adhered also show cytoplasmic Factor VIII immunostaining indicating its endothelial nature. Scale bar A−C=50 μm; Inset=25 μm; D×100; E×8000.