"5393","Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats","Several studies suggest that cyclooxygenase (COX)-2 plays a pivotal role in the progression of ischemic brain damage. In the present study, we investigated the effects of selective inhibition of COX-2 with nimesulide (12 mg/kg) and selective inhibition of COX-1 with valeryl salicylate (VAS, 12-120 mg/kg) on prostaglandin E2 (PGE2) levels, myeloperoxidase (MPO) activity, Evans Blue (EB) extravasation and infarct volume in a standardized model of transient focal cerebral ischemia in the rat. Postischemic treatment with nimesulide markedly reduced the increase in PGE2 levels in the ischemic cerebral cortex 24 h after stroke and diminished infarct size by 48 % with respect to vehicle-treated animals after 3 days of reperfusion. Furthermore, nimesulide significantly attenuated the blood-brain barrier (BBB) damage and leukocyte infiltration (as measured by EB leakage and MPO activity, respectively) seen at 48 h after the initial ischemic episode. These studies provide the first experimental evidence that COX-2 inhibition with nimesulide is able to limit BBB disruption and leukocyte infiltration following transient focal cerebral ischemia. Neuroprotection afforded by nimesulide is observed even when the treatment is delayed until 6 h after the onset of ischemia, confirming a wide therapeutic window of COX-2 inhibitors in experimental stroke. On the other hand, selective inhibition of COX-1 with VAS had no significant effect on the evaluated parameters. These data suggest that COX-2 activity, but not COX-1 activity, contributes to the progression of focal ischemic brain injury, and that the beneficial effects observed with non-selective COX inhibitors are probably associated to COX-2 rather than to COX-1 inhibition. ","http://cogprints.org/5393/","Candelario-Jalil, Eduardo and Gonzalez-Falcon, Armando and Garcia-Cabrera, Michel and Leon, Olga Sonia and Fiebich, Bernd","Murphy, Prof. Sean and Turner, Prof. Anthony","       <span class=\"person_name\">Candelario-Jalil, Eduardo</span> and <span class=\"person_name\">Gonzalez-Falcon, Armando</span> and <span class=\"person_name\">Garcia-Cabrera, Michel</span> and <span class=\"person_name\">Leon, Olga Sonia</span> and <span class=\"person_name\">Fiebich, Bernd</span>     (2007)  <a href=\"http://cogprints.org/5393/\"><em>Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats.</em></a>       [Journal (Paginated)]           ","","2007-02"