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

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Ye Z, Guo Q, Wang N, Xia P, Yuan Y, Wang E

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

Neurol Sci. 2012 Apr;33(2):239-49. doi: 10.1007/s10072-011-0665-6. Epub 2011 Jul 1.

PubMed ID

21720900 [ View in PubMed

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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.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sevoflurane	Mitochondrial potassium channel	Protein	Humans	Yes	Activator	Details