Cyclooxygenase-2 mediates hyperbaric oxygen preconditioning in the rat model of transient global cerebral ischemia.

Abstract

BACKGROUND AND PURPOSE:

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: Oumei Cheng, Robert P Ostrowski, Bihua Wu, Wenwu Liu, Chunhua Chen, John H Zhang
• Journal: Stroke (Stroke) Vol. 42 Issue 2 Pg. 484-90 (Feb 2011) ISSN: 1524-4628 [Electronic] United States
• PMID: 21164135 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Neuroprotective Agents
• Cyclooxygenase 2

Topics

• Animals
• Brain (blood supply, drug effects, enzymology)
• Cyclooxygenase 2 (physiology)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Disease Models, Animal
• Hyperbaric Oxygenation (methods)
• Ischemic Attack, Transient (enzymology, metabolism, therapy)
• Ischemic Preconditioning (methods)
• Male
• Neuroprotective Agents (administration & dosage, pharmacology)
• Rats
• Rats, Sprague-Dawley