A cyclooxygenase-2 inhibitor attenuates white matter damage in chronic cerebral ischemia

The effects of nimesulide, a cyclooxygenase-2 inhibitor, were examined during chronic cerebral hypoperfusion. After bilateral ligation of the common carotid arteries in 30 rats, 21 received dosages of 2 or 5 mg/kg nimesulide daily and nine received vehicle daily for 14 days. The serum was then analyzed biochemically, and pathological changes were estimated in the white matter by the emergence of major histocompatibility complex (MHC) antigen-immunoreactive activated microglia and white matter lesions. In the vehicle-treated animals, activated microglia and white matter lesions were observed. Following treatment with either 2 or 5mg/kg nimesulide, the magnitude of these changes was reduced (p < 0.001) without significant side effects. These results indicate a potential use for cyclooxygenase-2 inhibitors in cerebrovascular disease.