title: Sevoflurane Postconditioning Reduces Apoptosis by Activating the JAK-STAT Pathway After Transient Global Cerebral Ischemia in Rats.
abstract: BACKGROUND
  The antiapoptotic effects of sevoflurane postconditioning are responsible for neuroprotection against cerebral ischemia-reperfusion injury. Phosphorylation of the Janus family tyrosine kinases (JAK) 2-signal transducers and activators of transcription (STAT) 3 pathway is linked to antiapoptosis. Here, we determined whether the antiapoptotic effects of sevoflurane postconditioning are associated with activation of the JAK2-STAT3 pathway after global transient cerebral ischemia in rats.
  
  
  METHODS
  Forty-five rats were randomly assigned to 5 groups: sham (n=5), control (10 min of ischemia, n=10), sevoflurane postconditioning (2 periods of sevoflurane inhalation after ischemia for 10 min, n=10), AG490 (a JAK2 selective inhibitor, intraperitoneal administration of 40 mg/kg before ischemia, n=10), and sevoflurane postconditioning plus AG490 group (n=10). The number of apoptotic cells as well as the expression of JAK2, phosphorylated JAK2 (P-JAK2), STAT3, phosphorylated STAT3 (P-STAT3), Bcl-2 (antiapoptotic protein), and Bax (proapoptotic protein) were evaluated 3 days after ischemia.
  
  
  RESULTS
  The apoptotic cell count was significantly lower in the sevoflurane postconditioning group than in the control, AG490, and sevoflurane postconditioning plus AG490 groups. JAK2 and STAT3 levels were comparable among all 5 groups. P-JAK2, P-STAT3, and Bcl-2 levels were higher and Bax levels were lower in the sevoflurane postconditioning group relative to the control, AG490, and sevoflurane postconditioning plus AG490 groups.
  
  
  CONCLUSIONS
  Sevoflurane postconditioning reduced apoptosis by increasing P-JAK and P-STAT expression after transient global ischemia in rats, and AG490 reversed the beneficial antiapoptotic effects of sevoflurane postconditioning, suggesting that the JAK-STAT pathway may be involved in the antiapoptotic mechanism of sevoflurane postconditioning.
authors.affiliation: *Department of Anesthesiology and Pain Medicine, Keimyung University Dongsan Hospital, Keimyung University College of Medicine †Department of Anesthesiology and Pain Medicine, Hospital of Catholic University of Daegu, Daegu ‡Department of Anesthesiology and Pain Medicine, Seoul National University Hospital ∥Department of Anesthesiology and Pain Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul §Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
authors.forename: Hyun-Chang
authors.initials: HC
authors.lastname: Kim
authors.forename: Eugene
authors.initials: E
authors.lastname: Kim
authors.forename: Jung Il
authors.initials: JI
authors.lastname: Bae
authors.forename: Kook Hyun
authors.initials: KH
authors.lastname: Lee
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Jeon
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Hwang
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Lim
authors.forename: Seong-Won
authors.initials: SW
authors.lastname: Min
authors.forename: Hee-Pyoung
authors.initials: HP
authors.lastname: Park
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D053614:Janus Kinase 2 / Q000187:drug effects* / Q000235:genetics; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D050796:STAT3 Transcription Factor / Q000187:drug effects* / Q000235:genetics; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D018696:Neuroprotective Agents; D050796:STAT3 Transcription Factor; D000077149:Sevoflurane; D053614:Janus Kinase 2