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The prostaglandin synthesizing enzyme cyclooxygenase-2 (COX-2) is up-regulated in the brain of rodents during cerebral ischemia and contributes to ischemic brain injury. This study sought to determine whether COX-2 is also up-regulated in the human brain in the acute stages of cerebral ischemic infarction. Paraffin-embedded sections from patients who died 1-2 days following infarction in the middle cerebral artery territory were processed for COX-2 immunohistochemistry. COX-2 immunoreactivity was observed in infiltrating neutrophils, in vascular cells and in neurons located at the border of the infarct. The data suggest that COX-2 up-regulation is also relevant to cerebral ischemia in humans and raise the possibility that COX-2 reaction products participate in the mechanisms of ischemic injury also in the human brain.

Interferon regulatory factor-1 (IRF-1), a transcription factor that controls the expression of genes related to inflammation and injury, may be involved in the mechanisms of cerebral ischemia. In this study, we used immunohistochemistry to determine whether IRF-1 protein is up-regulated after cerebral ischemia, and to define the identity of the cells that express IRF-1 in the postischemic brain. In mice, IRF-1 immunoreactivity was present in intravascular neutrophils 24 h after middle cerebral artery occlusion. At 96 h, immunoreactivity was observed in neutrophils infiltrating the ischemic tissue and in neurons at the outer border of the ischemic territory. IRF-1 immunoreactivity was also found in neurons and inflammatory cells in the brain of patients who died 1-2 days after ischemic stroke. The neuronal expression of IRF-1, in conjunction with the finding that IRF-1 deletion is beneficial to the post-ischemic brain, suggests that expression of IRF-1-dependent genes in neurons plays a role in ischemic neuronal death.