MORPHOMETRIC STUDY OF FOCAL CEREBRAL-ISCHEMIA IN RATS - A STEREOLOGICAL EVALUATION

An efficient, unbiased stereological method for estimating and evaluat ing volumetric parameters of cortical infarction is presented. Long-Ev ans rats were subjected to a standard procedure for achieving focal ce rebral ischemia, consisting of permanent ligation of the right middle cerebral artery and temporary occlusion of both common carotid arterie s. Animals were killed 24 h later by perfusion fixation and the brains were embedded in celloidin, serially sectioned at 60 mu m and stained with Cresyl violet. All cases showed identifiable areas of infarction of variable extent within the territory of the right middle cerebral artery. Involvement of allocortical or subcortical structures was vari able and in three cases there were small foci of infarct in the contra lateral hemisphere. The absolute volumes of the infarcted tissue and o f the spared cortex of both hemispheres were obtained by means of an u nbiased estimator of volume based on Cavalieri's principle. The best e stimate of the actual amount of infarcted cortex was found to be given by the volume ratio between the spared cortex of the right (infarcted ) hemisphere and the total cortex of the left (control) hemisphere. Th is approach avoided the error introduced by the accompanying edema and decreased the observed interanimal variance. Sample size predictions for therapeutic-pharmacological trials show that relatively few animal s would be needed using the model of ischemia and quantitative morphom etry presented here to detect a 30-40% change in infarct volume.