We tested the hypothesis that increasing durations of focal ischemia that have been shown to result in enlargement of cortical infarct will be associated with progression of behavioral dysfunction that can be measured 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 hypertensive rats underwent 45, 60, 90, or 120 min of tandem middle cerebral and common carotid artery occlusion followed by reperfusion. We then evaluated the extent of damage and its recovery for up to 21 days using nine behavioral tests aimed at analyzing strength, coordination, and bilateral asymmetry. Also using a graded bioassay that employs a curve-fitting computer program (ALLFIT) to correlate duration of ischemia with degree of behavioral dysfunction, we calculated the average of maximal behavioral dysfunction and duration of ischemia required to produce half-maximal behavioral dysfunction and compared these values in untreated controls with analogous values obtained from animals treated with CNS-1102. Three behavioral tests, forearm flex, tape (somatosensory neutralization), and foot-fault placing, were each separately and combined able to distinguish between the degrees of damage produced by increasing 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 three tests. This analysis of behavioral dysfunction represents a useful experimental model to grade efficacy of therapies aimed at protecting the brain from damage produced by acute stroke and might also be used to assess recovery from preexisting ischemic damage.

Background and Purpose This study explored the correlation between duration of focal ischemia and infarct volume in spontaneously hypertensive rats as a measure of outcome after neuroprotective intervention.Methods We used 2,3,5 -triphenyltetrazolium chloride staining to discriminate infarcted tissue and calculate infarct volume 24 hours after temporary tandem common carotid/ middle cerebral artery occlusion lasting 5 to 150 minutes. We used a graded bioassay described by logistic function and executed by computer program (ALLFIT) to evaluate changes in infarct volume after increasing durations of ischemia. The method allowed us to calculate the maximal infarct volume (VoL^) and the duration of ischemia before reperfusion producing half-maximal infarct size (T,,,). Hypothermia and the N-methyl-D-aspartate antagonist CNS-1102 begun after