Tight junctions of the blood-brain barrier

1. The blood-brain barrier is essential for the maintenance and regulation of the neural microenvironment. The blood-brain barrier endothelial cells c omprise an extremely low rate of transcytotic vesicles and a restrictive pa racellular diffusion barrier. The latter is realized by the tight junctions between the endothelial cells of the brain microvasculature, which are sub ject of this review. Morphologically, blood-brain barrier-tight junctions a re more similar to epithelial tight junctions than to endothelial tight jun ctions in peripheral blood vessels. 2. Although blood-brain barrier-tight junctions share many characteristics with epithelial tight junctions, there are also essential differences. Howe ver, in contrast to tight junctions in epithelial systems, structural and f unctional characteristics of tight junctions in endothelial cells are highl y sensitive to ambient factors. 3. Many ubiquitous molecular constituents of tight junctions have been iden tified and characterized including claudins, occludin, ZO-1, ZO-2, ZO-3, ci ngulin, and 7H6. Signaling pathways involved in tight junction regulation c omprise, among others, G-proteins, serine, threonine, and tyrosine kinases, extra- and intracellular calcium levels, cAMP levels, proteases, and TNF a lpha. Common to most of these pathways is the modulation of cytoskeletal el ements which may define blood-brain barrier characteristics. Additionally, cross-talk between components of the tight junction- and the cadherin-calen in system suggests a close functional interdependence of the two cell-cell contact systems. 4. Recent studies were able to elucidate crucial aspects of the molecular b asis of tight junction regulation. An integration of new results into previ ous morphological work is the central intention of this review.