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PMID: 10690502 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Tight junctions of the blood-brain barrier.

Cellular and molecular neurobiology ·Vol. 20 ·No. 1 ·2000-02-00 ·Pages 57-76

Kniesel U, Wolburg H

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.

MeSH Terms
Animals Blood-Brain Barrier/physiology Brain/blood supply,cytology,metabolism Cells, Cultured Humans Membrane Proteins/metabolism Second Messenger Systems/physiology Signal Transduction/physiology Tight Junctions/metabolism,ultrastructure
Chemicals
Membrane Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kniesel U
Institute of Pathology, University of Tübingen, Germany.
Wolburg H
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Article Info
Journal
Cellular and molecular neurobiology
Abbr.
Cell Mol Neurobiol
ISSN
0272-4340
DOI
10.1023/a:1006995910836
Published
2000-02-00
Pages
57-76
Language
English
Region
United States
NLM ID
8200709
Subset
IM
External Links
PubMed source DOI: 10.1023/a:1006995910836 View journal details
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