Apoptosis Occurs in the Penumbra Zone during Short-Duration Focal Ischemia in the Rat

Abstract

To investigate the appearance of apoptosis in short-duration focal ischemia, the authors induced left middle cerebral artery (MCA) occlusion in male rats by insertion of an intraluminal suture. The total number of apoptotic cells was determined by hematoxylin-eosin staining and TUNEL labeling and confirmed by gel electrophoresis. The data indicate that the total number of apoptotic cells increased with ischemia duration (P = 0.0006), with most apoptotic cells located in the striatum of the ischemic hemisphere. As the duration of ischemia lengthened, necrosis became more prevalent and apoptosis receded to the periphery of the infarct. Using iodo[14C]-antipyrine to correlate the distribution of apoptosis to regional CBF (rCBF), the authors found that rCBF in the ischemic dorsolateral striatum was compatible with penumbra flow and significantly lower than the ventromedial striatum and frontoparietal cortex. This difference disappeared after 45 minutes of reperfusion. The authors conclude that focal ischemia of short duration results in changes compatible with apoptosis in regions of low rCBF, and this can occur without necrosis. This model is relevant to transient ischemic attack in the human and may suggest that, in addition to being a harbinger of stroke, transient ischemic attacks may cause histopathologic changes not yet clinically detectable.