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JCS ePress online publication date 23 Dec 2002
doi: 10.1242/jcs.00264

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Research Article

Protection against hypoxia-induced increase in blood-brain barrier permeability: role of tight junction proteins and NF{kappa}B


Rachel C. Brown, Karen S. Mark, Richard D. Egleton, Jason D. Huber, Amanda R. Burroughs, and Thomas P. Davis*
* Author for correspondence (e-mail: davistp{at}u.arizona.edu)

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 NF{kappa}B.




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