GRADED BIOASSAY FOR DEMONSTRATION OF BRAIN RESCUE FROM EXPERIMENTAL ACUTE-ISCHEMIA IN RATS

Background and Purpose This study explored the correlation between dur ation of focal ischemia and infarct volume in spontaneously hypertensi ve rats as a measure of outcome after neuroprotective intervention. Me thods We used 2,3,5-triphenyltetrazolium chloride staining to discrimi nate infarcted tissue and calculate infarct volume 24 hours after temp orary tandem common carotid/middle cerebral artery occlusion lasting 5 to 150 minutes. We used a graded bioassay described by logistic funct ion and executed by computer program (ALLFIT) to evaluate changes in i nfarct volume after increasing durations of ischemia. The method allow ed us to calculate the maximal infarct volume (Vol(max)) and the durat ion of ischemia before reperfusion producing half-maximal infarct size (T-50). Hypothermia and the N-methyl-D-aspartate antagonist CNS-1102 begun after the onset of ischemia were tested for their ability to red uce Vol(max) and prolong T-50 as analyzed by ALLFIT. Results Vol(max) was 180.6+/-22.4 mm(3) and T-50 was 45.9+/-5.8 minutes in control rats . Hypothermia (30 degrees C) applied during ischemia reduced Vol(max) by 66 mm(3) and extended T-50 by 50% (P<.05 for each comparison). CNS- 1102 like hypothermia, extended T-50 by 44% but did not have an effect on Vol(max). Conclusions Analysis of the changes of infarct size afte r increasing durations of ischemia indicates that although both were p rotective, the two treatments tested may exhibit different profiles of efficacy. This method of analyzing ischemia-induced damage may be ver y sensitive for studying the efficacy and possible clinical use of neu ronal protective therapies for hyperacute stroke.