General Anesthetics Inhibit Erythropoietin Induction under Hypoxic Conditions in the Mouse Brain 英文参考文献.docVIP

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General Anesthetics Inhibit Erythropoietin Induction under Hypoxic Conditions in the Mouse Brain 英文参考文献.doc

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General Anesthetics Inhibit Erythropoietin Induction under Hypoxic Conditions in the Mouse Brain 英文参考文献

GeneralAnestheticsInhibitErythropoietinInduction underHypoxicConditionsintheMouseBrain TomoharuTanaka1*,ShinichiKai1,TomohiroKoyama1,HirokiDaijo1,TakehikoAdachi2 ,Kazuhiko Fukuda1,KiichiHirota1* 1Department of Anesthesia, Kyoto University Hospital, Kyoto, Japan, 2Department of Anesthesia, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan Abstract Background:Erythropoietin(EPO),originallyidentifiedasahematopoieticgrowthfactorproducedinthekidneyandfetal liver,isalsoendogenouslyexpressedinthecentralnervoussystem(CNS).EPOintheCNS,mainlyproducedinastrocytes,is induced under hypoxic conditions in a hypoxia-inducible factor (HIF)-dependent manner and plays a dominant role in neuroprotectionandneurogenesis.WeinvestigatedtheeffectofgeneralanestheticsonEPOexpressioninthemousebrain andprimaryculturedastrocytes. Methodology/Principal Findings: BALB/c mice were exposed to 10% oxygen with isoflurane at various concentrations (0.10–1.0%). Expression of EPO mRNA in the brain was studied, and the effects of sevoflurane, halothane, nitrous oxide, pentobarbital, ketamine, and propofol were investigated. In addition, expression of HIF-2a protein was studied by immunoblotting. Hypoxia-induced EPO mRNA expression in the brain was significantly suppressed by isoflurane in a concentration-dependent manner. A similar effect was confirmed for all other general anesthetics. Hypoxia-inducible expressionofHIF-2aproteinwasalsosignificantlysuppressedwithisoflurane.Intheexperimentsusingprimarycultured astrocytes, isoflurane, pentobarbital, and ketamine suppressed hypoxia-inducible expression of HIF-2a protein and EPO mRNA. Conclusions/Significance: Taken together, our results indicate that general anesthetics suppress activation of HIF-2 and inhibithypoxia-inducedEPOupregulationinthemousebrainthroughadirecteffectonastrocytes. Citation:TanakaT,KaiS,KoyamaT,DaijoH,AdachiT,etal.(2011)GeneralAnestheticsInhibitErythropoietinInductionunderHypoxicConditionsintheMouse Brain.PLoSON