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Abstract

1. The blood-brain barrier is essential for the maintenance and regulation of the neural microenvironment. The blood-brain barrier endothelial cells comprise an extremely low rate of transcytotic vesicles and a restrictive paracellular diffusion barrier. The latter is realized by the tight junctions between the endothelial cells of the brain microvasculature, which are subject of this review. Morphologically, blood-brain barrier-tight junctions are more similar to epithelial tight junctions than to endothelial tight junctions in peripheral blood vessels. 2. Although blood-brain barrier-tight junctions share many characteristics with epithelial tight junctions, there are also essential differences. However, in contrast to tight junctions in epithelial systems, structural and functional characteristics of tight junctions in endothelial cells are highly sensitive to ambient factors. 3. Many ubiquitous molecular constituents of tight junctions have been identified and characterized including claudins, occludin, ZO-1, ZO-2, ZO-3, cingulin, and 7H6. Signaling pathways involved in tight junction regulation comprise, among others, G-proteins, serine, threonine, and tyrosine kinases, extra- and intracellular calcium levels, cAMP levels, proteases, and TNF alpha. Common to most of these pathways is the modulation of cytoskeletal elements which may define blood-brain barrier characteristics. Additionally, cross-talk between components of the tight junction- and the cadherin-catenin 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 basis of tight junction regulation. An integration of new results into previous morphological work is the central intention of this review.

A Transmembrane Tight Junction Protein Selectively Expressed on Endothelial Cells and Platelets

“…Paracellular permeability across endothelial or epithelial cell layers is determined by tight junctions that seal the intercellular space (6). Tight junctions show ion and size selectivity, and their barrier function varies in tightness between epithelial and endothelial cells and also between endothelia in different types of blood vessels and different tissues (7). To understand how the paracellular permeability of tight junctions is regulated and how they are formed, we need to know their molecular composition.…”

<b><i>Panax notoginseng</i></b> Saponins Ameliorate Leukocyte Adherence and Cerebrovascular Endothelial Barrier Breakdown upon Ischemia-Reperfusion in Mice

“…The endothelial tight junction helps maintain brain homeostasis via allowing the essential molecules through and preventing potentially dangerous substances from crossing the BBB [23]. Occludin, claudins, junctional adhesion molecules, ZOs, and other proteins constitute the tight junction complex, among which ZO-1, occludin, and claudin-5 are tightly associated with BBB disruption induced by leucocyte recruitment in ischemic stroke [6].…”

The Blood–Brain Barrier: An Introduction to Its Structure and Function

“…Brain capillaries exhibit some fundamental differences compared to peripheral capillaries. Whereas peripheral capillaries are fenestrated with gaps up to 50 nm wide the endothelial cells of brain capillaries are closely connected to each other by tight junctions and zonulae occludentes [40,41]. In addition, the number of mitochondria is about five to ten times higher than in cells of peripheral microvessels, indicating a high metabolic activity [42][43][44].…”

“…Three types of junctions are found: Adherens junctions [106], tight junctions [41,107,108], and possibly gap junctions [80,[109][110][111].…”