title: Sevoflurane pre- and post-conditioning protect the brain via the mitochondrial K ATP channel.
abstract: BACKGROUND
  This study aimed to evaluate whether exposure to sevoflurane at the onset of reperfusion provides protection similar to sevoflurane preconditioning and whether the effect depends on mitochondrial potassium ATP-dependent channel (mitoK(ATP)) in a rat model of focal cerebral ischaemia.
  
  
  METHODS
  Adult Wistar male rats were subjected to focal cerebral ischaemia for 1 h followed by 24 h or 7 days of reperfusion. Preconditioning consisted of 15 min exposure to sevoflurane at 1 minimum alveolar concentration (2.6%) 72 h before ischaemia. Post-conditioning was performed by exposure to sevoflurane immediately at the onset of reperfusion or by a delayed exposure 5 min after the onset of reperfusion. The role of the mitoK(ATP) channel was assessed by i.p. injection of the selective blocker 5-hydroxydecanoate before each sevoflurane administration or by the mitoK(ATP) channel opener, diazoxide (DZX), given in place of sevoflurane. Cerebral infarct size, neurological deficit score, and motor coordination were evaluated 24 h and 7 days after reperfusion.
  
  
  RESULTS
  Sevoflurane preconditioning and early post-conditioning reduced both cerebral infarct size and neurological defect score at 24 h of reperfusion whereas the sole sevoflurane post-conditioning improved motor coordination. At 7 days, only infarct volume remained lower in pre- and post-conditioned animals. Neuroprotection mediated by sevoflurane was lost when it was given 5 min after the onset of reperfusion and was abolished by inhibition of mitoK(ATP). DZX alone mimicked sevoflurane-induced pre- and post-conditioning.
  
  
  CONCLUSIONS
  The pretreatment with sevoflurane or its early administration at reperfusion provides neuroprotection via mitoK(ATP) in a rat model of focal cerebral ischaemia.
authors.affiliation: Department of Pharmacology, Lille 2 University Medical School, France.
authors.forename: S
authors.initials: S
authors.lastname: Adamczyk
authors.forename: E
authors.initials: E
authors.lastname: Robin
authors.forename: M
authors.initials: M
authors.lastname: Simerabet
authors.forename: E
authors.initials: E
authors.lastname: Kipnis
authors.forename: B
authors.initials: B
authors.lastname: Tavernier
authors.forename: B
authors.initials: B
authors.lastname: Vallet
authors.forename: R
authors.initials: R
authors.lastname: Bordet
authors.forename: G
authors.initials: G
authors.lastname: Lebuffe
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D002245:Carbon Dioxide / Q000097:blood; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D006439:Hemodynamics / Q000187:drug effects; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D018696:Neuroprotective Agents; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D002245:Carbon Dioxide; D000077149:Sevoflurane; D010100:Oxygen