title: Sevoflurane-induced delayed neuroprotection involves mitoK(ATP) channel opening and PKC ε activation.
abstract: There is an increasing body of evidence that a brief exposure to anesthesia induces ischemic tolerance in rat brain (anesthetic preconditioning). However, it is unknown whether preconditioning with sevoflurane, a commonly used volatile anesthetic in current clinical practice, produces a delayed window of neuroprotection against ischemia and what the mechanisms are for this protection. To address these issues, adult male Sprague-Dawley rats were subjected to middle cerebral arterial occlusion (MCAO) for 2 h. Sevoflurane preconditioning was induced 24 h before brain ischemia by exposing the animals to sevoflurane at 1.0 minimum alveolar concentration (2.4%) in oxygen for 60 min. Animals preconditioned with sevoflurane had lower neurological deficit scores and smaller brain infarct volumes than animals with brain ischemia at 6 and 24 h after MCAO, respectively. Application of a selective antagonist for mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel, 5-hydroxydecanoate (5-HD, 40 mg/kg i.p.) 30 min before sevoflurane exposure attenuated this beneficial effect. Moreover, protein kinase C ε (PKC ε) was translocated to the membrane fraction at 6 h, but not 24 h, after brain reperfusion in animals preconditioned with sevoflurane and this effect was also abolished by 5-HD. We concluded that sevoflurane preconditioning induces a delayed neuroprotection and that mitochondrial K(ATP) channels and PKC ε may be involved in this neuroprotection.
authors.affiliation: Department of Anesthesiology, The Affiliated Xiangya Hospital of Center South University, Changsha, 410078, Hunan, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ye
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Huang
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: Zhi-Yi
authors.initials: ZY
authors.lastname: Zuo
authors.forename: Qu-Lian
authors.initials: QL
authors.lastname: Guo
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects*; D019194:Ischemic Preconditioning; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D000077149:Sevoflurane
chemical_list: D008738:Methyl Ethers; D018696:Neuroprotective Agents; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D000077149:Sevoflurane; D051744:Protein Kinase C-epsilon; D010100:Oxygen