title: Postconditioning in focal cerebral ischemia: role of the mitochondrial ATP-dependent potassium channel.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Lille Medical School, University of Lille 2, Lille, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Robin
authors.forename: Malika
authors.initials: M
authors.lastname: Simerabet
authors.forename: Sidi Mohammed
authors.initials: SM
authors.lastname: Hassoun
authors.forename: Sebastien
authors.initials: S
authors.lastname: Adamczyk
authors.forename: Benoit
authors.initials: B
authors.lastname: Tavernier
authors.forename: Benoit
authors.initials: B
authors.lastname: Vallet
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.forename: Gilles
authors.initials: G
authors.lastname: Lebuffe
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D057775:Ischemic Postconditioning; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D020768:Middle Cerebral Artery / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D009048:Motor Skills; D009422:Nervous System Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D010101:Oxygen Consumption / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control
chemical_list: D003652:Decanoic Acids; D006880:Hydroxy Acids; D054086:KATP Channels; D026902:Potassium Channel Blockers; C052853:5-hydroxydecanoic acid; D002118:Calcium