Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice

Cyclooxygenase-2 (COX-2), a prostanoid-synthesizing enzyme that contributes to the toxicity associated with inflammation, has recently emerged as a pr omising therapeutic target for several illnesses, ranging from osteoarthrit is to Alzheimer's disease. Although COX-2 has also been linked to ischemic stroke, its role in the mechanisms of ischemic brain injury remains controv ersial. We demonstrate that COX-2-deficient mice have a significant reducti on in the brain injury produced by occlusion of the middle cerebral artery, The protection can be attributed to attenuation of glutamate neurotoxicity , a critical factor in the initiation of ischemic brain injury, and to abro gation of the deleterious effects of postischemic inflammation, a process c ontributing to the secondary progression of the damage. Thus, COX-2 is invo lved in pathogenic events occurring in both the early and late stages of ce rebral ischemia and may be a valuable therapeutic target for treatment of h uman stroke.