title: Activation of K(2)P channel-TREK1 mediates the neuroprotection induced by sevoflurane preconditioning.
abstract: BACKGROUND
  Preconditioning with volatile anaesthetic agents induces tolerance to focal cerebral ischaemia, although the underlying mechanisms have not been clearly defined. The present study analyses whether TREK-1, a two-pore domain K(+) channel and target for volatile anaesthetics, plays a role in mediating neuroprotection by sevoflurane.
  
  
  METHODS
  Differentiated SH-SY5Y cells were preconditioning with sevoflurane and challenged by oxygen-glucose deprivation (OGD). Cell viability and expression of caspase-3 and TREK-1 were evaluated. Rats that were preconditioned with sevoflurane were subjected to middle cerebral artery occlusion (MCAO), and the expression of TREK-1 protein and mRNA was analysed. Neurological scores were evaluated and infarction volume was examined.
  
  
  RESULTS
  Sevoflurane preconditioning reduced cell death in differentiated SH-SY5Y cells challenged by OGD. Sevoflurane preconditioning reduced infarct volume and improved neurological outcome in rats subjected to MCAO. Sevoflurane preconditioning increased levels of TREK-1 mRNA and protein. Knockdown of TREK-1 significantly attenuated sevoflurane preconditioning-induced neuroprotective effects in vitro and in vivo.
  
  
  CONCLUSIONS
  Sevoflurane preconditioning-induced neuroprotective effects against transient cerebral ischaemic injuries involve TREK-1 channels. These results suggest a novel mechanism for sevoflurane preconditioning-induced tolerance to focal cerebral ischaemia.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Xi'an, Shanxi 710032, China.
authors.forename: L
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Xi'an, Shanxi 710032, China.
authors.forename: M
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Xi'an, Shanxi 710032, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Xi'an, Shanxi 710032, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Xi'an, Shanxi 710032, China.
authors.forename: B
authors.initials: B
authors.lastname: Su
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Xi'an, Shanxi 710032, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Xi'an, Shanxi 710032, China hldong6@hotmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Dong
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000517:prevention & control*; D002248:Carbon Monoxide / Q000097:blood; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D055785:Gene Knockdown Techniques; D006801:Humans; 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; D024683:Potassium Channels, Tandem Pore Domain / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D000077149:Sevoflurane; D014407:Tumor Cells, Cultured
chemical_list: D008738:Methyl Ethers; D018696:Neuroprotective Agents; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C103742:potassium channel protein TREK-1; D000077149:Sevoflurane; D002248:Carbon Monoxide; D010100:Oxygen
keywords: TREK-1; anaesthetics volatile, sevoflurane; brain, ischaemia; neuroprotection; preconditioning