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: Zhi Ye, Qulian Guo, Na Wang, Pingping Xia, Yajing Yuan, E Wang
• Journal: Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology (Neurol Sci) Vol. 33 Issue 2 Pg. 239-49 (Apr 2012) ISSN: 1590-3478 [Electronic] Italy
• PMID: 21720900 (Publication Type: Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Decanoic Acids
• Hydroxy Acids
• Methyl Ethers
• Neuroprotective Agents
• Potassium Channels
• mitochondrial K(ATP) channel
• Sevoflurane
• 5-hydroxydecanoic acid
• p38 Mitogen-Activated Protein Kinases

Topics

• Analysis of Variance
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Brain Infarction (etiology, prevention & control)
• Cell Count
• Decanoic Acids (pharmacology)
• Disease Models, Animal
• Gene Expression Regulation (drug effects)
• Hydroxy Acids (pharmacology)
• Infarction, Middle Cerebral Artery (drug therapy)
• Ischemic Preconditioning (methods)
• Male
• Methyl Ethers (therapeutic use)
• Neuroprotective Agents (therapeutic use)
• Phosphorylation (drug effects)
• Potassium Channels (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sevoflurane
• Time Factors
• p38 Mitogen-Activated Protein Kinases (metabolism)