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Tight Junctions and the Blood-Brain Barrier

  • Chapter
Tight Junctions

Abstract

The blood-brain barrier protects the neural microenvironment from changes of the blood composition. It is located in the endothelium which is both seamless and interconnected by tight junctions. The restrictive paracellular diffusion barrier goes along with an extremely low rate of transcytosis and the expression of a high number of channels and transporters for such molecules which cannot enter or leave the brain paracellularly.

Many tight junction molecules have been identified and characterized including claudins, occludin, ZO-1, ZO-2, ZO-3, cingulin, 7H6, JAM and ESAM. Signaling pathways involved in tight junction regulation include G-proteins, serine-, threonine-, and tyrosine-kinases, extra- and intracellular calcium levels, cAMP levels, proteases, and cytokines Most of these pathways modulate the connection of the cytoskeletal elements to the tight junction transmembrane molecules. Additionally, crosstalk between components of the tight junction- and the cadherin-catenin-system of the adherens junction suggests a close functional interdependence of the two cell-cell-contact systems.

The blood-brain barrier endothelial cells are situated on top of a basal lamina which contains various molecules of the extracellular matrix. Pericytes and astrocytes directly contact this basal lamina; however, little is known about the signaling pathways between these cell types and the endothelium which possibly are mediated by components of the basal lamina. To understand the interplay between astrocytes, pericytes, the basal lamina and the endothelial cells is a big challenge for understanding the blood-brain barrier in the future.

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Authors and Affiliations

  1. Institute of Pathology, University of Tübingen, Tübingen, Germany

    Hartwig Wolburg

  2. Max Delbrück-Center Berlin-Buch Department of Neurology, Schering AG Berlin, Berlin, Germany

    Andrea Lippoldt

  3. Institute of Cell Biology ZMBE, University of Münster, Münster, Germany

    Klaus Ebnet

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  1. Hartwig Wolburg
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  2. Andrea Lippoldt
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  3. Klaus Ebnet
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Wolburg, H., Lippoldt, A., Ebnet, K. (2006). Tight Junctions and the Blood-Brain Barrier. In: Tight Junctions. Springer, Boston, MA. https://doi.org/10.1007/0-387-36673-3_13

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