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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., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Reactive oxygen species (ROS) and the mitochondrial ATP-dependent potassium channel (mitoK(+)(-)(ATP)) play a major role in myocardial preconditioning. The same pathways seem to be involved in cerebral preconditioning. The aim of this study was to evaluate ROS involvement during the initial phase of delayed preconditioning and its relationship with mitoK(+)(-ATP) opening in a rat model of cerebral ischemia-reperfusion. Ischemia was induced by a 1-h occlusion of middle cerebral artery followed by a 24-h reperfusion period. A delayed preconditioning was induced by a 3-min ischemia (IPC), an in situ infusion of hydrogen peroxide (H(2)O(2)), or an administration of mitoK(+)(-ATP) agonist diazoxide, 72 h before the ischemia-reperfusion (I/R). IPC was performed in the presence or not of N-acetyl-cysteine (NAC) or 5-hydroxydecanoate (5-HD). A neuroprotection was induced by IPC and administration of H(2)O(2) or diazoxide. The decrease in infarct size was respectively 24.5%, 45.7% and 24.6%. IPC was abolished by 5-HD and NAC, indicating that mitoK(+)(-ATP) and ROS are involved. The protection induced by H(2)O(2) was blocked by 5-HD and diazoxide triggering was abolished by NAC. This strong relationship between ROS and mitoK(+)(-ATP) needs to be clarified as ROS might be involved both upstream and downstream of mitoK(+)(-ATP) opening.