Neuroprotection by the selective cyclooxygenase-2 inhibitor SC-236 results in improvements in behavioral deficits induced by reversible spinal cord ischemia

Stroke; a Journal of Cerebral Circulation
P A LapchakJ A Zivin

Abstract

Cyclooxygenase-2 (COX-2), an enzyme that is induced in the central nervous system after various insults, has been localized to neurons and in cells associated with the cerebral vasculature, where it may be involved in the inflammatory component of the ischemic cascade. COX-2 is part of the initial reaction that involves the arachidonic acid cascade, which produces molecules that support an inflammatory response. The present study evaluated the pharmacological effects of a specific long-acting COX-2 inhibitor, SC-236, in a reversible rabbit spinal cord ischemia model using clinical rating scores (behavioral analysis) as the primary end point. SC-236 was administered (10 to 100 mg/kg SC) 5 minutes after the start of occlusion to groups of rabbits exposed to ischemia induced by temporary (10 to 40 minutes) occlusion of the infrarenal aorta. Behavioral analysis, which allowed for the calculation of an ET(50) value representing the duration of ischemia (minutes) associated with a 50% probability of resultant permanent paraplegia, was conducted 18 and 48 hours later. A drug was determined to be neuroprotective if it prolonged the ET(50) significantly compared with the appropriate control group. Since SC-236 is not readily soluble in ...Continue Reading

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