الفهرس 
AcknowledgmentOnly 14 pages are availabe for public view
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Abstract
Ischaemic cerebrovascular disease is one of the leading causes of death or longtime disability. A number of studies have reported that COX2 may be a crucial component in ischaemiainduced neurodegeneration.This experimental study was carried to evaluate the effect of selective COX2 inhibitor rofecoxib in a rat model of permanent focal cerebral ischaemia, and to compare its protective effect with the already used neuroprotective drug calcium channel blocker nimodipine. Also, to detect and to quantify early postischaemic pathophysiological markers using the transient global cerebral ischaemia rat model. Furthermore, we tried to intensify the probable antiischaemic effect of selective COX2 inhibitor by its combination with selective blockers of other detrimental pathways involved in cerebral ischaemia. First group: Evaluation of the antiischaemic effect of selective COX2 inhibitor (rofecoxib) in permenant focal cerebral ischaemia model: The animals in this group were subjected for the following tests: 1Neurobehavioral tests. 2 Reflex plasma renin activity 3Delineation of the infarction areas using 2,3,5 tripheny1 tetrazolium chloride (TTC) stain or histopathological changes in the ipsilateral hippocampus by modified Glees method Our results indicated that both the selective COX2 inhibitor rofecoxib and the calcium channel blocker nimodipine showed nearly equal improvement in the neurological score, decrease in the infarction size and hippocampal degenerative changes in this model of MCA occlusion. Also, they decreased the reflex PRA to a level below that of sham group suggesting the important role of COX2 in reflex basal renin secretion. This may provide a basis for new therapeutic strategies for the COX2 inhibitor in the prevention and treatment of stroke. So, further clinical trials with the COX2 inhibitor in stroke is recommended. Second group: Testing the intensification of the antiischaemic effect of selective COX 2 inhibitor (rofecoxib) in transient global cerebral ischaemia model: 24 hours after induction of global ischaemia and reperfusion. The rats were decapitated. The forebrain of both hemispheres from each rat was removed and divided to equal three thirds for assay of. 1 Nitric oxide 2 Prostaglandin E2 3 Malondialdehyde Rofecoxib caused significant attenuation of all the raised ischaemic parameters in the forebrain tissue as PGE2, NO and MDA 24 hours of reperfusion.The combinations between rofecoxib and nimodipine or cerestat showed significant attenuation of the brain PGE2, NO and MDA levels 24 hours of reperfusion following transient global cerebral ischemia in comparison to that of groups treated with rofecoxib alone.