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Astrocyte mediated modulation of blood-brain barrier permeability does not correlate with a loss of tight junction proteins from the cellular contacts

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Abstract

In the central nervous system (CNS) complex endothelial tight junctions (TJs) form a restrictive paracellular diffusion barrier, the blood-brain barrier (BBB). Pathogenic changes within the CNS are frequently accompanied by the loss of BBB properties, resulting in brain edema. In order to investigate whether BBB leakiness can be monitored by a loss of TJ proteins from cellular borders, we used an in vitro BBB model where brain endothelial cells in co-culture with astrocytes form a tight permeability barrier for 3H-inulin and 14C-sucrose. Removal of astrocytes from the co-culture resulted in an increased permeability to small tracers across the brain endothelial cell monolayer and an opening of the TJs to horseradish peroxidase as detected by electron microscopy. Strikingly, opening of the endothelial TJs was not accompanied by any visible change in the molecular composition of endothelial TJs as junctional localization of the TJ-associated proteins claudin-3, claudin-5, occludin, ZO-1 or ZO-2 or the adherens junction-associated proteins β-catenin or p120cas did not change. Thus, opening of BBB TJs is not readily accompanied by the complete loss of the junctional localization of TJ proteins.

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Acknowledgements

We thank Urban Deutsch, Friedemann Kiefer and Dietmar Vestweber for helpful discussions with the manuscript.

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Author notes

  1. Stefan Hamm

    Present address: Wyeth Vaccine Research, Pearl River, NY, USA

Authors and Affiliations

  1. Max Planck Institute for Physiological and Clinical Research, Bad Nauheim, Germany

    Stefan Hamm, Bénédicte Dehouck, Jörg Kraus, Karen Wolburg-Buchholz & Britta Engelhardt

  2. Max Planck Institute for Vascular Biology, Münster, Germany

    Jörg Kraus & Britta Engelhardt

  3. Unité mixte Institut Pasteur de Lille-Université d’Artois, U.A. 2465-Faculté des Sciences Jean Perrin, Lens, France

    Bénédicte Dehouck, Roméo Cecchelli & Marie-Pierre Dehouck

  4. Theodor Kocher Institute, University of Bern, Freiestrasse 1, 3012, Bern, Switzerland

    Britta Engelhardt

  5. Institute for Pathology, Tübingen, Germany

    Karen Wolburg-Buchholz & Hartwig Wolburg

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  1. Stefan Hamm
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  2. Bénédicte Dehouck
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Correspondence to Britta Engelhardt.

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This work is dedicated to the memory of Werner Risau (died 13.12.1998), who initiated this collaboration

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Hamm, S., Dehouck, B., Kraus, J. et al. Astrocyte mediated modulation of blood-brain barrier permeability does not correlate with a loss of tight junction proteins from the cellular contacts. Cell Tissue Res 315, 157–166 (2004). https://doi.org/10.1007/s00441-003-0825-y

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  • DOI: https://doi.org/10.1007/s00441-003-0825-y

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