Delayed neuroprotection induced by sevoflurane via opening mitochondrial ATP-sensitive potassium channels and p38 MAPK phosphorylation

• Published in: Neurological sciences 2012-04, Vol.33 (2), p.239-249
• Main Authors: Ye, Zhi, Guo, Qulian, Wang, Na, Xia, Pingping, Yuan, Yajing, Wang, E.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Anti-Arrhythmia Agents - pharmacology; Brain; Brain Infarction - etiology; Brain Infarction - prevention & control; Cell Count; Cerebral blood flow; Cerebral infarction; Channel opening; Chloride; Decanoic Acids - pharmacology; Disease Models, Animal; Gene Expression Regulation - drug effects; Hydroxy Acids - pharmacology; Infarction, Middle Cerebral Artery - drug therapy; Ischemia; Ischemic Preconditioning - methods; Male; MAP kinase; Medicine; Medicine & Public Health; Methyl Ethers - therapeutic use; Mitochondria; Neurological diseases; Neurology; Neuroprotection; Neuroprotective Agents - therapeutic use; Neuroradiology; Neurosciences; Neurosurgery; Original Article; Oxygen; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Phosphorylation - drug effects; Potassium channels; Potassium Channels - metabolism; Psychiatry; Rats; Rats, Sprague-Dawley; Reperfusion; Sevoflurane; Signal transduction; Time Factors
• ISSN: 1590-1874; 1590-3478
• DOI: 10.1007/s10072-011-0665-6

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.