| First Author | Doré S | Year | 2003 |
| Journal | Ann Neurol | Volume | 54 |
| Issue | 2 | Pages | 155-62 |
| PubMed ID | 12891667 | Mgi Jnum | J:156166 |
| Mgi Id | MGI:4418924 | Doi | 10.1002/ana.10612 |
| Citation | Dore S, et al. (2003) Neuronal overexpression of cyclooxygenase-2 increases cerebral infarction. Ann Neurol 54(2):155-62 |
| abstractText | 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. |
