title: Sevoflurane Preconditioning Confers Neuroprotection via Anti-apoptosis Effects.
abstract: Neuroprotection against cerebral ischemia afforded by volatile anesthetic preconditioning (APC) has been demonstrated both in vivo and in vitro, yet the underlying mechanism is poorly understood. We previously reported that repeated sevoflurane APC reduced infarct size in rats after focal ischemia. In this study, we investigated whether inhibition of apoptotic signaling cascades contributes to sevoflurane APC-induced neuroprotection. Male Sprague-Dawley rats were exposed to ambient air or 2.4 % sevoflurane for 30 min per day for 4 consecutive days and then subjected to occlusion of the middle cerebral artery (MCAO) for 60 min at 24 h after the last sevoflurane intervention. APC with sevoflurane markedly decreased apoptotic cell death in rat brains, which was accompanied by decreased caspase-3 cleavage and cytochrome c release. The apoptotic suppression was associated with increased ratios of anti-apoptotic Bcl-2 family proteins over pro-apoptotic proteins and with decreased activation of JNK and p53 pathways. Thus, our data suggest that suppression of apoptotic cell death contributes to the neuroprotection against ischemic brain injury conferred by sevoflurane preconditioning.
authors.affiliation: Department of Anesthesiology, Huashan Hospital, Shanghai, China.|State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors.forename: Hailian
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology of Shanghai Pulmonary Hospital, Tongji University, Shanghai, 200433, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology, Huashan Hospital, Shanghai, China.|State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.|Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China. ZhanFx2@upmc.edu.|Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA. ZhanFx2@upmc.edu.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China. yqgao@shmu.edu.cn.|Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA. yqgao@shmu.edu.cn.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Gao
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D019194:Ischemic Preconditioning; D048670:MAP Kinase Kinase 4 / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects; D051020:bcl-X Protein / Q000187:drug effects / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; C000617196:Bcl2 protein, rat; C494813:Bcl2l1 protein, rat; D008738:Methyl Ethers; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D000077149:Sevoflurane; D048670:MAP Kinase Kinase 4
keywords: Apoptosis; Cerebral ischemia; Neuroprotection; Sevoflurane; Volatile anesthetic preconditioning