AN ALTERNATIVE METHOD FOR THE QUANTITATION OF NEURONAL DAMAGE AFTER EXPERIMENTAL MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS - ANALYSIS OF BEHAVIORAL DEFICIT

We tested the hypothesis that increasing durations of focal ischemia t hat have been shown to result in enlargement of cortical infarct will be associated with progression of behavioral dysfunction that can be m easured by a battery of tests sufficiently sensitive and reproducible to detect a positive effect of pharmacotherapy. Untreated or N-methyl- D-aspartate receptor antagonist (CNS-1102)-treated spontaneously hyper tensive rats underwent 45, 60, 90, or 120 min of tandem middle cerebra l and common carotid artery occlusion followed by reperfusion. We then evaluated the extent of damage and its recovery for up to 21 days usi ng nine behavioral tests aimed at analyzing strength, coordination, an d bilateral asymmetry. Also using a graded bioassay that employs a cur ve-fitting computer program (ALLFIT) to correlate duration of ischemia with degree of behavioral dysfunction, we calculated the average maxi mal behavioral dysfunction and duration of ischemia required to produc e half-maximal behavioral dysfunction and compared these values in unt reated controls with analogous values obtained from animals treated wi th CNS-1102. Three behavioral tests, forearm flex, tape (somatosensory neutralization), and foot-fault placing, were each separately and com bined able to distinguish between the degrees of damage produced by in creasing durations of ischemia, The behavioral abnormalities assessed using the tape test were reversible within a week, whereas those using forearm flex or foot-fault tests persisted for at least 21 days. CNS- 1102 significantly reduced behavioral dysfunction measured by all thre e tests. This analysis of behavioral dysfunction represents a useful e xperimental model to grade efficacy of therapies aimed at protecting t he brain from damage produced by acute stroke and might also be used t o assess recovery from preexisting ischemic damage.