FIG. 2.

The mammalian blood–brain barrier (BBB) and structural components of endothelial tight junctions (TJs). (A) The BBB in development. Mouse embryo (day 13 after conception), microperfused with Trypan blue and fixed with PFA. The dye (bound to plasma proteins) stains all parts of the body with exception of the brain and the spinal cord. This suggests that at this early stage of development the BBB is functional at least for proteins (10). The arrow indicates a slight staining in the developing choroid plexus. (B) Schematic drawing of the neurovascular unit. Cerebral endothelial cells are tightly connected by tight junctions. Pericytes are in close contact with the endothelial cells. A basal lamina surrounds both endothelial cells and pericytes. Capillary walls are ensheathed by astrocytic end feet. Occasionally, neurites are also in direct contact with capillaries and so are microglia. Afp, astrocytic foot process; BL, basal lamina; cEC, cerebral endothelial cell; CL, capillary lumen; MG, microglia; n, nucleus; PC, pericyte, TJ, tight junction. (C) Integral proteins locating at endothelial TJs. Peripheral junctional proteins may be subdivided into three classes: i) Adaptors and scaffolding proteins, ii) regulatory and signaling proteins, and iii) transcriptional and posttranscriptional regulators. AJs, adherens junctions; ESAM (endothelial cell-specific adhesion molecule); JAMs, junctional adhesion molecules; TJs, tight junctions. (To see this illustration in color, the reader is referred to the web version of this article at www.liebertonline.com/ars).