CYCLOOXYGENASE-2 INHIBITION PREVENTS DELAYED DEATH OF CA1 HIPPOCAMPAL-NEURONS FOLLOWING GLOBAL-ISCHEMIA

The inducible isoform of the enzyme cyclooxygenase-2 (COX2) is an imme diate early gene induced by synaptic activity in the brain. COX2 activ ity is an important mediator of inflammation, but it is not known whet her COX2 activity is pathogenic in brain. To study the role of COX2 ac tivity in ischemic injury in brain, expression of COX2 mRNA and protei n and the effect of treatment with a COX2 inhibitor on neuronal surviv al in a rat model of global ischemia were determined. Expression of bo th COX2 mRNA and protein was increased after ischemia in CA1 hippocamp al neurons before their death. There was increased survival of CA1 neu rons in rats treated with the COX2-selective inhibitor SC58125 {1-[(4- methylsulfonyl) phenyl]-3-trifluoro-methyl-5-[(4-fluoro)phenyl] pyrazo le} before or after global ischemia compared with vehicle controls. Fu rthermore, hippocampal prostaglandin E-2 concentrations 24 h after glo bal ischemia were decreased in drug-treated animals compared with vehi cle-treated controls. These results suggest that COX2 activity contrib utes to CA1 neuronal death after global ischemia.