title: Sevoflurane postconditioning attenuates cerebral ischemia-reperfusion injury via protein kinase B/nuclear factor-erythroid 2-related factor 2 pathway activation.
abstract: Oxidative damage plays a critical role in many diseases of the central nervous system. This study was conducted to determine the molecular mechanisms involved in the putative anti-oxidative effects of sevoflurane against experimental stroke. Focal cerebral ischemia was performed via 1h of middle cerebral artery occlusion followed by reperfusion. At the onset of reperfusion, rats were subjected to postconditioning with sevoflurane or without sevoflurane for 1h. Neurological deficit score was assessed at different time points after reperfusion. Cerebral infarct volume, oxidative stress level and the binding activity of Nrf2 to antioxidant response element were assessed, meanwhile the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), quinine oxidoreductase 1 (NQO1), protein kinase B (Akt) and phosphor-Akt was examined by Western blot at 72h after reperfusion. Sevoflurane postconditioning administration significantly reduced neurological deficit score, infarct volume and oxidative stress levels, while increased the expression of phosphorylation Akt, NQO1, Nrf2 and the binding activity of Nrf2 to ARE in middle cerebral artery occlusion rats. These neuroprotective effects were all suppressed by LY294002, a selective PI3K blocker. Taken together, these findings provided evidence that sevoflurane postconditioning protects brain against ischemic/reperfusion injury, and this neuroprotective effect involves the Akt/Nrf2 pathway.
authors.affiliation: Department of Anesthesiology, The Second Hospital of TianJin Medical University, Tianjin 300211, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Hospital of TianJin Medical University, Tianjin 300211, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, The Second Hospital of TianJin Medical University, Tianjin 300211, PR China.
authors.forename: Guoyi
authors.initials: G
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, General Hospital of TianJin Medical University, Tianjin 300052, PR China. Electronic address: sanpi1020@sina.com.
authors.forename: Yonghao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, General Hospital of TianJin Medical University, Tianjin 300052, PR China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, General Hospital of TianJin Medical University, Tianjin 300052, PR China.
authors.forename: Keliang
authors.initials: K
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology, General Hospital of TianJin Medical University, Tianjin 300052, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Anesthesiology, General Hospital of TianJin Medical University, Tianjin 300052, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008738:Methyl Ethers / Q000627:therapeutic use*; D050983:NF-E2 Transcription Factor / Q000378:metabolism; D009460:Neurologic Examination; D018384:Oxidative Stress / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects*; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D008738:Methyl Ethers; D050983:NF-E2 Transcription Factor; D010975:Platelet Aggregation Inhibitors; D000077149:Sevoflurane; D051057:Proto-Oncogene Proteins c-akt
keywords: Ischemia-reperfusion injury; Nrf2; P-Akt; Sevoflurane postconditioning