EFFECTS OF STREPTOZOTOCIN-INDUCED HYPERGLYCEMIA ON BRAIN-DAMAGE FOLLOWING TRANSIENT ISCHEMIA

Hyperglycemia is known to aggravate ischemic brain damage. The present experiments were undertaken to explore whether hyperglycemia caused b y streptozotocin-induced diabetes exacerbates brain damage following t ransient brain ischemia as it does in animals acutely infused with glu cose. Experimental diabetes was induced by injection of streptozotocin in rats which were subjected to in min of forebrain ischemia either 1 week(1-wk) or 4 weeks (4-wk) after the induction of diabetes. Normogl ycemic rats exposed to the same duration of ischemia and sham-operated diabetic rats served as controls. The animals underwent evaluation of clinical outcome and histopathological analysis of brain damage. Post ischemic seizures developed in 35.3 and 42.1% of l-wk and 4-wk diabeti c hyperglycemic animals, respectively. The incidence of seizure was no t different between the two groups. None of the diabetic animals with plasma glucose concentrations below 12 mM exhibited seizure activity. The extent and distribution of brain damage were similar between 1- an d 4-wk diabetic animals. In the CA1 and in the subicular regions of hi ppocampus, both diabetic hyperglycemic and normoglycemic animals showe d 70-80% cell death. Diabetic hyperglycemic animals had more severe ne uronal necrosis in the parietal cortex than normoglycemic animals. In diabetic hyperglycemic animals, neuronal damage involved additional br ain structures, e.g., cingulate cortex, thalamus nuclei, substantia ni gra, pars reticulata, and the hippocampal CA3 sector, i.e., structures in which neurons were not affected in normoglycemic ischemic subjects at this duration of ischemia. These findings demonstrate that diabeti c hyperglycemic animals frequently develop postischemic seizures and t hat streptozotocin-induced hyperglycemia results in exacerbated postis chemic brain damage of the same density and distribution as in acutely glucose-infused animals. (C) 1998 Academic Press.