Apoptosis in the adult striatum after transient forebrain ischemia and the effects of ischemic severity.

The mechanisms of neuronal injury after cerebral ischemia have been under active investigation. The medium-size neurons in the dorsal striatum die within 24 h after transient cerebral ischemia. Using electron microscopy, the present study examined the nature of neuronal death in the striatum of adult rats following transient forebrain ischemia and tested the hypothesis that the ischemic severity might influence the nature of cell death. After severe ischemia (approximately 21 min ischemic depolarization), most neurons in the dorsal striatum died with swollen organelles and small irregular chromatin clumps resembling necrosis. The tissue damage in the dorsomedial striatum was less severe than that in the dorsolateral striatum and approximately 5% of the neurons in this region died with large chromatin clumps and relatively intact organelles resembling apoptosis. Some neurons displayed a mixture of necrotic- and apoptotic-like appearance. In contrast, the neurons with large somata only exhibited mild ultrastructural changes. After moderate ischemia (approximately 15 min ischemic depolarization), the tissue damage was less severe and the process of necrosis was temporally prolonged compared with that after severe ischemia. The apoptotic-like neuronal death was observed not only in the dorsomedial (approximately 6%) but also in the dorsolateral striatum (approximately 7%). The neurons in the striatum showed transient reversible changes after mild ischemia (approximately 10 min ischemic depolarization). The present study demonstrates that both apoptosis and necrosis occur in the adult striatum following transient forebrain ischemia and apoptosis occurs in the regions with less severe ischemia. These results suggest that ischemic severity might be one of the contributing factors to necrosis or apoptosis following transient global ischemia.