sc-236 and Infarction--Middle-Cerebral-Artery

Increases in COX-2 enzymatic activity and prostaglandin production have been associated with neuronal injury in both acute and age-related degenerative neurological diseases. In this study, we tested the effects of increased COX-2 activity in a model of transient focal ischemia using a transgenic mouse model in which human COX-2 is constitutively expressed selectively in neurons of the striatum, cerebral cortex, and hippocampus. These COX-2 transgenic mice harbor elevated levels of PGE(2) that are 10-fold higher than nontransgenic levels. A significant increase in infarct volume was observed after middle cerebral artery occlusion with 4 days of reperfusion in COX-2 transgenic mice as compared with nontransgenic littermates. Pretreatment of nontransgenic mice with the selective COX-2 inhibitor SC58236 resulted in a significant reduction of infarct volume in nontransgenic mice, consistent with previous pharmacological studies. However, transgenic COX-2 mice treated with SC58236 did not show a significant reduction. This suggests that chronic increases in COX-2 expression and enzymatic activity, which can occur in aging and in pathological states characterized by oxidative stress and chronic inflammatory processes, can lead to downstream cellular changes that have a negative impact on neuronal survival in cerebrovascular disease.

Topics: Animals; Blood Gas Analysis; Blotting, Western; Body Temperature; Cerebrovascular Circulation; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Humans; Immunoenzyme Techniques; Immunohistochemistry; Infarction, Middle Cerebral Artery; Isoenzymes; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Reperfusion Injury; Sulfonamides