title: Isoflurane enhanced hemorrhagic transformation by impairing antioxidant enzymes in hyperglycemic rats with middle cerebral artery occlusion.
abstract: OBJECTIVE
  Because the potential neuroprotective effect of isoflurane is controversial, we attempted to study whether isoflurane after treatment provides neuroprotection in a rat model of hyperglycemia-induced ischemic hemorrhagic transformation.
  
  
  METHODS
  Rats received an injection of 50% dextrose (6 mL/kg intraperitoneally) and had a middle cerebral artery occlusion 30 minutes later. Four groups were included: sham-operated, ischemia/reperfusion, isoflurane treatment, and vehicle groups. In the treatment group, after 2 hours of ischemia, 2% isoflurane was administered at the onset of reperfusion. We measured the level of blood glucose at 0, 2.5, 4.5, and 6.5 hours after dextrose injection. Infarct and hemorrhagic volumes, neurological scores, oxidative stress (malondialdehyde, 4-hydroxy-2-nonenal, and nitrotyrosine) and the activities of superoxide dismutase and catalase were measured at 24 hours after ischemia.
  
  
  RESULTS
  Isoflurane had no effects on blood glucose, it failed to reduce infarct, hemorrhage volume, and brain edema, and it enhanced neurobehavioral deficits when compared with the ischemia/reperfusion group at 24 hours after middle cerebral artery occlusion. On the contrary, isoflurane exacerbated these parameters compared with the vehicle group. In addition, it increased the expressions of malondialdehyde, 4-hydroxy-2-nonenal, and nitrotyrosine, and it decreased the activities of superoxide dismutase and catalase compared to the vehicle group.
  
  
  CONCLUSIONS
  Isoflurane after treatment worsened physiological and neurological outcomes in this ischemia hyperglycemia-induced hemorrhagic transformation possibly by impairing the antioxidant defense system.
authors.affiliation: Department of Anatomy and Embryology, Peking University Health Science Center, Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhan
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: He
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.forename: Changman
authors.initials: C
authors.lastname: Zhou
authors.forename: John
authors.initials: J
authors.lastname: Zhang
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications / Q000209:etiology; D002374:Catalase / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D006943:Hyperglycemia / Q000150:complications / Q000503:physiopathology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy*; D007530:Isoflurane / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D000975:Antioxidants; D018696:Neuroprotective Agents; D007530:Isoflurane; D002374:Catalase; D013482:Superoxide Dismutase