title: Cyclooxygenase-2 mediates hyperbaric oxygen preconditioning in the rat model of transient global cerebral ischemia.
abstract: OBJECTIVE
  Hyperbaric oxygen (HBO) preconditioning (PC) allows brain protection against transient global ischemia. In the present study, we hypothesize that the mechanism of HBO-PC involves the induction of cyclooxygenase-2 (COX-2) in cerebral tissues before ischemia, which leads to a suppression of COX-2 and its downstream targets after global ischemic insult.
  
  
  METHODS
  One hundred twenty-nine male Sprague Dawley rats (body weight 280-300 grams) were allocated to the naive control group and the sham operation group, and 3 groups of animals were subjected to 15-minute 4-vessel occlusion: untreated, preconditioned with HBO 2.5 atmospheres absolutes for 1 hour daily for 5 days, preconditioned as mentioned and administered with COX-2 inhibitor NS-398 (1 mg/kg body weight intraperitoneal) before each preconditioning session, and normal rats preconditioned with HBO without ischemia. The mortality, the incidence of seizures, and T-maze scores were recorded. The quantitative cell count in Nissl stain and TUNEL was conducted on day 7 after ischemia. The brain expression of COX-2 was analyzed with Western blotting and immunofluorescence staining.
  
  
  RESULTS
  HBO-PC increased the number of surviving neurons in the Cornu Ammonis area 1, which was associated with the reduced COX-2 expression in the hippocampus and in the cerebral cortex at 1 and 3 days after ischemia. HBO-PC improved functional performance and tended to decrease mortality and the frequency of seizures. These beneficial effects of HBO-PC were abolished by the COX-2 selective inhibitor NS-398.
  
  
  CONCLUSIONS
  HBO-PC reduced COX-2 expression and provided brain protection after global ischemia. Administration of COX-2 inhibitor with HBO before ischemia abolished preconditioning effect, thereby implicating COX-2 as a mediator of HBO-PC in the ischemic brain.
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Oumei
authors.initials: O
authors.lastname: Cheng
authors.forename: Robert P
authors.initials: RP
authors.lastname: Ostrowski
authors.forename: Bihua
authors.initials: B
authors.lastname: Wu
authors.forename: Wenwu
authors.initials: W
authors.lastname: Liu
authors.forename: Chunhua
authors.initials: C
authors.lastname: Chen
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D006931:Hyperbaric Oxygenation / Q000379:methods*; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000378:metabolism / Q000628:therapy*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D018696:Neuroprotective Agents; D051546:Cyclooxygenase 2