title: Neuroprotection of Sevoflurane Against Ischemia/Reperfusion-Induced Brain Injury Through Inhibiting JNK3/Caspase-3 by Enhancing Akt Signaling Pathway.
abstract: In this study, we investigated the neuroprotective effect of sevoflurane against ischemic brain injury and its underlying molecular mechanisms. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. The rats were pretreated with sevoflurane alone or sevoflurane combined with LY294002/wortmannin (selective inhibitor of PI3K) before ischemia. Cresyl violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. Immunoblotting and immunoprecipitation were performed to measure the phosphorylation of Akt1, PRAS40, ASK1, and JNK3 and the expression of cleaved-caspase-3. The results demonstrated that a moderate dose of sevoflurane inhalation of 2% for 2 h had significant neuroprotective effects against ischemia/reperfusion induced hippocampal neuron death. Sevoflurane significantly increased Akt and PRAS40 phosphorylation and decreased the phosphorylation of ASK1 at 6 h after reperfusion and the phosphorylation of JNK3 at 3 days after reperfusion following 15 min of transient global brain ischemia. Conversely, LY294002 and wortmannin significantly inhibited the effects of sevoflurane. Taken together, the results suggest that sevoflurane could suppress ischemic brain injury by downregulating the activation of the ASK1/JNK3 cascade via increasing the phosphorylation of Akt1 during ischemia/reperfusion.
authors: Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.|School of Basic Education Sciences, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Xiang-Ru
authors: XR
authors: Wen
authors: Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.|Department of Genetics, Research Center for Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Yan-Yan
authors: YY
authors: Fu
authors: Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Hong-Zhi
authors: HZ
authors: Liu
authors: Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.|Department of Genetics, Research Center for Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Jian
authors: J
authors: Wu
authors: School of Public Health, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Xiao-Ping
authors: XP
authors: Shao
authors: School of Public Health, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Xun-Bao
authors: XB
authors: Zhang
authors: Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Man
authors: M
authors: Tang
authors: School of Public Health, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Yue
authors: Y
authors: Shi
authors: Department of Medical Information, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Kai
authors: K
authors: Ma
authors: Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Fang
authors: F
authors: Zhang
authors: School of Public Health, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Yi-Wen
authors: YW
authors: Wang
authors: School of Public Health, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Hui
authors: H
authors: Tang
authors: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China.
authors: Dong
authors: D
authors: Han
authors: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, 221002, People's Republic of China.
authors: Pu
authors: P
authors: Zhang
authors: Department of Respiratory Medicine, The Affiliated Municipal Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, 221002, People's Republic of China.
authors: Shu-Ling
authors: SL
authors: Wang
authors: School of Basic Education Sciences, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China. xuzhou@xzmc.edu.cn.
authors: Zhou
authors: Z
authors: Xu
authors: Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, People's Republic of China. biosongyuanjian@126.com.|Department of Genetics, Research Center for Neurobiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People's Republic of China. biosongyuanjian@126.com.
authors: Yuan-Jian
authors: YJ
authors: Song
mesh_terms: D000730:Androstadienes / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use; D004789:Enzyme Activation / Q000187:drug effects; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology / Q000627:therapeutic use*; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000066829:Neuroprotection / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002867:Chromones; D008738:Methyl Ethers; D009025:Morpholines; D018696:Neuroprotective Agents; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000077149:Sevoflurane; D048057:Mitogen-Activated Protein Kinase 10; D048848:MAP Kinase Kinase Kinase 5; D053148:Caspase 3; D000077191:Wortmannin
keywords: Akt1; Caspase-3; Ischemia/reperfusion; JNK3; Sevoflurane