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• W2082425573 abstract "In order to further explore the mechanisms by which activation of mitochondrial ATP-sensitive potassium channels (mitoKATP) confers neuroprotection, we investigated the role of the mitochondrial permeability transition pore (MPTP) in in vivo and in vitro models. Adult male Sprague-Dawley rats were exposed to 90 min of middle cerebral artery occlusion (MCAO) followed by reperfusion for 22 h, when neurological scores and infarct volumes were evaluated. Activating mitoKATP by infusion of 2 mmol/L diazoxide into the ventricles 20 min before MCAO or inhibiting the MPTP by infusion of 1 μmol/L cyclosporin A 15 min before reperfusion significantly increased functional score and reduced infarction volume. Subsequent intracerebroventricular infusion of 2 mmol/L atractyloside, the MPTP opener, 10 min before reperfusion significantly attenuated the neuroprotective effects of diazoxide and cyclosporin A. The swelling of mitochondria isolated from brain was evaluated by spectrophotometry and served as a measure of MPTP opening. In isolated mitochondria, 100 μmol/L atractyloside attenuated the decrease of mitochondrial swelling induced by 30 μmol/L diazoxide or cyclosporin A (0.5 or 1 μmol/L). Furthermore, 100 μmol/L diazoxide or 1 μmol/L cyclosporin A both attenuated the fluorescence intensity in isolated mitochondria loaded with rhod-2 acetoxymethylester, and 100 μmol/L atractyloside abolished the effects of diazoxide and cyclosporin A. These results suggest that activation of mitoKATP protects the brain against injury, and this is probably mediated by attenuating mitochondrial Ca2+ overload and thus inhibiting MPTP opening during brain ischemia and reperfusion." @default.
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• W2082425573 date "2006-07-01" @default.
• W2082425573 modified "2023-10-14" @default.
• W2082425573 title "The neuroprotection conferred by activating the mitochondrial ATP-sensitive K+ channel is mediated by inhibiting the mitochondrial permeability transition pore" @default.
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• W2082425573 doi "https://doi.org/10.1016/j.neulet.2006.04.001" @default.
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