Protection against hypoxia-induced increase in blood-brain barrier permeability: role of tight junction proteins and NFκB

Author:

Brown Rachel C.1,Mark Karen S.1,Egleton Richard D.1,Huber Jason D.1,Burroughs Amanda R.1,Davis Thomas P.1

Affiliation:

1. Department of Pharmacology, The University of Arizona College of Medicine, Tucson, AZ, USA

Abstract

Co-culture with glial cells and glia-conditioned media can induce blood-brain barrier properties in microvessel endothelial cells and protect against hypoxia-induced blood-brain barrier breakdown. We examined the effect of two types of glia-conditioned media on brain microvessel endothelial cell permeability and tight junction protein expression, and studied potential mechanisms of action. We found that C6-glioma-conditioned media, but not rat astrocyte-conditioned media, protected against an increase in permeability induced by exposure to 1% oxygen for 24 hours. This hypoxic stress caused an increase in the expression of tight junction proteins claudin-1 and actin,particularly in cells treated with C6-conditioned media. We found that C6-conditioned media has a significantly higher level of both basic fibroblast growth factor and vascular endothelial growth factor. Treatment with C6-conditioned media for 1 or 3 days protects against hypoxia-induced permeability increases, and this protective effect may be mediated by signal transduction pathways terminating at the transcription factor NFκB.

Publisher

The Company of Biologists

Subject

Cell Biology

Reference49 articles.

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