Effect of astroglial cells on hypoxia-induced permeability in PBMEC cells.
An in vitro model of the blood-brain barrier (BBB), consisting of porcine brain-derived microvascular endothelial cells (PBMEC), was used to evaluate the effect of astrocytes in the BBB disruption during hypoxia. Hypoxia-induced hyperpermeability was decreased significantly in a coculture model of astroglia cells, either astrocytes or C6 glioma cells, with PBMEC and, to the same extent, when glia cell-conditioned medium was used. Corresponding to effects on hypoxia-induced hyperpermeability, astrocyte- and C6 cell-conditioned medium diminished hypoxia-induced vascular endothelial growth factor (VEGF) mRNA and protein expression, which recently was shown to be responsible for hypoxia-induced permeability changes in vitro. The effect on hypoxia-induced hyperpermeability and VEGF expression was specific for astroglia cells because conditioned medium from bovine smooth muscle cells (BSMC) did not show any effect. Immunocytochemistry revealed that 24 h of hypoxia disrupted the continuity of the tight junction protein, zonula occludens-1 (ZO-1), which lines the cytoplasmic face of intact tight junctions. These changes were prevented when hypoxia was performed in glia cell-conditioned medium. Results suggest that astrocytes protect the BBB from hypoxia-induced paracellular permeability changes by decreasing hypoxia-induced VEGF expression in microvascular endothelial cells.
Fischer
S
S
Department of Anesthesiology and Intensive Care, Max-Planck Institute for Physiological and Clinical Research, D-61231 Bad Nauheim, Germany. s.fischer@kerckhoff.mpg.de
Wobben
M
M
Kleinstück
J
J
Renz
D
D
Schaper
W
W
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply* / Q000166:cytology; D015687:Cell Hypoxia / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D008833:Microcirculation / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013552:Swine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D062826:Zonula Occludens-1 Protein
D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D008222:Lymphokines; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D062826:Zonula Occludens-1 Protein; D009569:Nitric Oxide