1. Protection against hypoxia-induced increase in blood-brain barrier permeability: role of tight junction proteins and NFkappaB.
- Author
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Brown RC, Mark KS, Egleton RD, Huber JD, Burroughs AR, and Davis TP
- Subjects
- Actins metabolism, Animals, Astrocytes metabolism, Blood-Brain Barrier drug effects, Cattle, Claudin-1, Culture Media, Conditioned pharmacology, Endothelial Growth Factors metabolism, Endothelium, Vascular drug effects, Fibroblast Growth Factor 2 metabolism, Hypoxia, Brain genetics, Hypoxia, Brain physiopathology, Intercellular Signaling Peptides and Proteins metabolism, Lymphokines metabolism, Microcirculation drug effects, Rats, Signal Transduction drug effects, Signal Transduction physiology, Stress, Physiological genetics, Stress, Physiological metabolism, Tight Junctions drug effects, Tumor Cells, Cultured, Up-Regulation drug effects, Up-Regulation physiology, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Blood-Brain Barrier physiology, Endothelium, Vascular metabolism, Hypoxia, Brain metabolism, Membrane Proteins metabolism, Microcirculation metabolism, NF-kappa B metabolism, Tight Junctions metabolism
- 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 NFkappaB.
- Published
- 2003
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