title: Hypothermia abolishes hypoxia-induced hyperpermeability in brain microvessel endothelial cells.
abstract: The effect of mild (32 degrees C) and deep (22 degrees C) hypothermia on hypoxia-induced hyperpermeability was examined using an in vitro model of brain derived microvascular endothelial cells (BMEC). It was shown that hypoxia-induced hyperpermeability to inulin across the BMEC monolayer was completely abolished at 32 degrees C and 22 degrees C for up to 24 h of hypoxia. During normoxia, no influence of hypothermia on BMEC monolayer permeability was observed. The hypoxia-induced decrease of the cyclic AMP level after 6 h was abolished at 32 degrees C as well as at 22 degrees C of hypoxia. But after 24 h of hypoxia, hypothermia did no longer prevent the hypoxia-induced decrease of the cAMP level, which suggests that the effect of hypothermia on hypoxia-induced hyperpermeability is not caused by maintenance of the cAMP level. Because vascular endothelial growth factor (VEGF) has been shown to be the mediator of hypoxia-induced permeability changes of BMEC via the release of nitric oxide (NO), the effect of hypothermia on the VEGF expression was evaluated. During normoxia, hypothermia did not change the VEGF expression significantly but the hypoxia-induced increase in VEGF mRNA and protein expression was completely abolished at 32 degrees C and 22 degrees C respectively. Accordingly, the hypoxia-induced increase of the cGMP level was depressed by hypothermia, which demonstrates that also the amount of NO released during hypoxia is decreased at lower temperatures. Results suggest that deep as well as mild hypothermia decreased hypoxia-induced hyperpermeability by lowering the expression of the permeability-increasing protein VEGF and with it the release of NO.
authors.affiliation: Max-Planck Institute for Physiological and Clinical Research, Department of Anesthesiology and Intensive Care, 61231 Bad Nauheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Fischer
authors.forename: D
authors.initials: D
authors.lastname: Renz
authors.forename: M
authors.initials: M
authors.lastname: Wiesnet
authors.forename: W
authors.initials: W
authors.lastname: Schaper
authors.forename: G F
authors.initials: GF
authors.lastname: Karliczek
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003080:Cold Temperature; D000242:Cyclic AMP / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006162:Guanylate Cyclase / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D019344:Lactic Acid / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013552:Swine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D006162:Guanylate Cyclase