title: Delayed neuroprotection induced by sevoflurane via opening mitochondrial ATP-sensitive potassium channels and p38 MAPK phosphorylation.
abstract: This study aimed to investigate the role of p38 MAPK phosphorylation and opening of the mitoK(ATP) channels in the sevoflurane-induced delayed neuroprotection in the rat brain. Adult male Sprague-Dawley rats (250-300 g) were randomly assigned into four groups: ischemia/reperfusion (Control), sevoflurane (Sevo), 5-hydroxydecanoate (5-HD) + sevoflurane (5-HD + Sevo) and 5-HD groups and were subjected to right middle cerebral artery occlusion (MCAO) for 2 h. Sevoflurane preconditioning was induced 24 h before MCAO in sevoflurane and 5-HD + sevoflurane groups by exposing the animals to 2.4% sevoflurane in oxygen for 60 min. In control and 5-HD groups: animals were exposed to oxygen for 60 min at 24 h before MCAO. A selective mitoK(ATP) channel antagonist, 5-hydroxydecanoate (5-HD, 40 mg/kg, i.p.), was administered 30 min before sevoflurane/oxygen exposure in the 5-HD + sevoflurane and 5-HD groups, respectively. Neurological deficits scores and the protein expression of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were evaluated at 24 and 72 h after reperfusion. Cerebral infarct size was evaluated at 72 h after reperfusion by 2,3,5-triphenyltetrazolium chloride staining. Sevoflurane preconditioning produced marked improvement neurological functions and a reduction in brain infarct volumes than animals with brain ischemia only. Sevoflurane treatment also caused increased phosphorylation of p38 MAPK at 24 and 72 h after reperfusion. These beneficial effects were attenuated by 5-HD. Blockade of cerebral protection with 5-HD concomitant with decrease in p38 phosphorylation suggests that mitoK(ATP) channels opening and p38 phosphorylation participate signal transduction cascade of sevoflurane preconditioning and p38 MAPK activation may be a downstream of opening mitoK(ATP) channels.
authors: Department of Anesthesioloy, The Affiliated Xiangya Hospital of Center South University, Changsha, 410078, Hunan Province, China.
authors: Zhi
authors: Z
authors: Ye
authors: Qulian
authors: Q
authors: Guo
authors: Na
authors: N
authors: Wang
authors: Pingping
authors: P
authors: Xia
authors: Yajing
authors: Y
authors: Yuan
authors: E
authors: E
authors: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D002452:Cell Count; D003652:Decanoic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D019194:Ischemic Preconditioning / Q000379:methods; D008297:Male; D008738:Methyl Ethers / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D008738:Methyl Ethers; D018696:Neuroprotective Agents; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D000077149:Sevoflurane; C052853:5-hydroxydecanoic acid; D048051:p38 Mitogen-Activated Protein Kinases