Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats

Candelario-Jalil, Eduardo and Gonzalez-Falcon, Armando and Garcia-Cabrera, Michel and Leon, Olga Sonia and Fiebich, Bernd (2007) Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats. [Journal (Paginated)]

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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.

Item Type:Journal (Paginated)
Keywords:Cyclooxygenase; prostaglandin E2; stroke; blood-brain barrier; leukocyte infiltration; cerebral ischemia; vasogenic edema; cerebral infarct; neuroprotection; prostanoids; COX-2; COX-1; neurodegeneration
Subjects:Neuroscience > Neurochemistry
ID Code:5393
Deposited By:Candelario-Jalil, Dr Eduardo
Deposited On:19 Feb 2007
Last Modified:11 Mar 2011 08:56

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