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Postconditioning in focal cerebral ischemia: role of the mitochondrial ATP-dependent potassium channel.

Abstract：

INTRODUCTION:Ischemic postconditioning (IpostC) has been described in both heart and brain. The first aim of this study was to evaluate the effects of IpostC on brain infarct size and neurological function in the middle cerebral artery occlusion (MCAO) model. The second aim was to determine the involvement of the mitochondrial potassium ATP-dependent channel (mitoK(ATP)) opening and its capacity to improve mitochondrial dysfunction induced by ischemia-reperfusion. METHODS:Wistar rats were subjected to 60min MCAO followed by 24-h reperfusion. Postconditioning was performed by 3 cycles of 30-s occlusion-reperfusion at the onset of reperfusion. Three behavioral tests were performed following 24h of reperfusion. Involvement of mitoK(ATP) was determined by the modulation of IpostC effects by 5-hydroxydecanoate (5-HD) and diazoxide. Mitochondrial function after 24h of reperfusion on isolated mitochondria was assessed through mitochondrial oxygen consumption, mitochondrial membrane potential and calcium retention capacity to evaluate impact of IpostC on mitochondrial permeability transition pore (MPTP) opening. RESULTS:IpostC resulted in a 40% decrease in infarct size and improved neurological outcome. These effects were lost when IpostC was delayed by 5min. The administration of diazoxide resulted in a 60% in infarct size. The beneficial effects of IpostC and diazoxide were blocked by 5-HD. Furthermore, 5-HD also blocked the inhibition of MPTP opening by IpostC and diazoxide. The hyperpolarization induced by ischemia-reperfusion was corrected by IpostC without any effect on oxidative phosphorylation. CONCLUSION:Our results confirm ischemic postconditioning-induced neuroprotection. They also support the involvement of mitoK(ATP) opening and its role in inhibiting the opening of MTPT induced by postconditioning.

journal_name

Brain Res

journal_title

Brain research

authors

Robin E,Simerabet M,Hassoun SM,Adamczyk S,Tavernier B,Vallet B,Bordet R,Lebuffe G

doi

10.1016/j.brainres.2010.12.054

subject

Has Abstract

pub_date

2011-02-23 00:00:00

pages

137-46

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(10)02741-1

journal_volume

1375

pub_type

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