Evaluation of the anti-ischaemic effect of selective COX-2 inhibitor [rofecoxib] in permanent left middle cerebral artery occlusion [focal cerebral ischemia model] in rats

ABSTRACT

Cyclooxygenase-2 [COX-2] enzyme is induced in the central nervous system after various insults. It has been localized to neurons and in cells associated with the cerebral vasculature where the system is involved in the inflammatory component of the ischaemic cascade. COX-2 is part of the initial reaction that involves the arachidonic acid cascade, which produces molecules that involved in inflammatory response. The present of study evaluated the pharmacological effects of a specific COX-2 inhibitor [rofecoxib], in a permanent focal cerebral ischaemia model in albino rats and its effects were compared to those of calcium channel blocker [nimodipine]. Experiments were carried out on sixty male albino rats. Focal cerebral ischemia was induced by middle cerebral artery occlusion. Rofecoxib and nimodipine were administered 30 minutes after the occlusion of middle cerebral artery [MCA] and then daily IP for successive 6 days during which neurobehavioral evaluation was done. On the 7[th] day of occlusion, the infarction size, was measure and the remote hippocampal cell death were determined. Treatment with either rofecoxib or nimodipine caused significant equal improvement of the neurological score, significant attenuation of the infarction size and hippocampal cell death. While, the decrease of the infarction size was 50% by both drugs, the percentage of reduction of hippocampal degeneration was only 10% by both drugs. This difference in the percentage of improvement of infarction sizes and hippocampal degeneration may be due to presence of the hippocampus in a remote site from MCA blood supply. The present study suggests that COX-2 plays an important role in the ischaemic cascade of events. Furthermore, selective COX-2 inhibitors may be useful in the treatment of ischaemic stroke to improve motor functions