Tight junctions brain capillary endothelium

Unlike adherens junctions, which form homophilic intercellular adhesion sites, tight junctions are complex structures recognized as being the molecular site of pericellular transport and its regulation. In addition to adherens and tight junctions, brain capillary endothelial cells have transmembrane receptors for matrix proteins (e.g., integrins). Impairment of either cell-cell or cell-matrix interactions can disrupt the BBB, in processes that parallel those of the peripheral endothelium. However, such impairments occur much less frequently in the brain. 

The brain capillary endothelium comprises the lumenal and ablumenal membranes of capillaries, which are separated by approximately 300 ran of endothelial cytoplasm (Figure 13.2). The structural differences between brain capillary endothelium and non-brain capillary endothelium are associated with the endothelial tight junctions. The non-brain capillaries have fenestrations (openings) between the endothelial cells through which solutes can move readily via passive diffusion. In brain capillaries, the endothelium has epithelial-like tight junctions which preclude movement via paracellular diffusion pathways. There is also minimal pinocytosis across brain capillary endothelim, which further limits transport of moieties from blood to brain. 

The main component of the blood-brain barrier is the brain endothelium, which exhibits a physical, an efflux and a metabolic barrier for the transport of drugs into the CNS. The physical barrier, an efflux, is a result of the tight junctions between adjacent endothelial cells, which are around 50-100 times tighter than in the peripheral endothelium, so that penetration across the endothelium is effectively confined to transcellular mechanisms [26, 27]. These junctions significantly restrict even the movement of small ions such as Na" " and Cl , so that the transendothelial electrical resistance (TEER), which is typically 2-20 2 cm in peripheral capillaries, can be over 1000 1 cm in brain endothelium [28]. 

Fig. 1 Anatomical makeup of the blood-brain barrier. Endothelial cells of the cerebral capillaries are tightly joined by complexes of tight junctions. Pericytes are found surrounding the capillary endothelium and are continuous with the basement membrane of the endothelium. The astrocytic endfeet are wrapped tightly around both pericytes and endothelial cells. Together, these cells work together to tightly regulate the influx/efflux and metabolism of molecules important for optimal brain function. Figure was reprinted, with permission [243]...

---