The roles of cyclooxygenase-1 in microglial activation

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Previously, we reported that ¹¹C-labeled ketoprofen-methyl ester (KTP-Me), a derivative of COX-1 selective inhibitor, could visualize the activation of microglia in rat model of neuroinflammation. In order to assess the hypothesis that COX-1 may play a crucial role in neuroinflammation, we evaluated the involvement of COX-1 in neuronal damages after transient middle cerebral artery occlusion (t-MCAO) in mice and rats. PET images with [¹¹C]KTP-Me were well correlated with the time-dependent changes of activated microglia in ischemic region after t-MCAO. The studies using COX-1 knockout mice revealed that the deficiency of COX-1 reduced neuroinflammation but exacerbated neurotoxicity induced by t-MCAO. These results raise the possibility that COX-1 may be involved in the neuroprotective functions after focal cerebral ischemia.