title: Effects of streptozotocin-induced hyperglycemia on brain damage following transient ischemia.
abstract: Hyperglycemia is known to aggravate ischemic brain damage. The present experiments were undertaken to explore whether hyperglycemia caused by streptozotocin-induced diabetes exacerbates brain damage following transient brain ischemia as it does in animals acutely infused with glucose. Experimental diabetes was induced by injection of streptozotocin in rats which were subjected to 10 min of forebrain ischemia either 1 week (1-wk) or 4 weeks (4-wk) after the induction of diabetes. Normoglycemic 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. Postischemic seizures developed in 35.3 and 42.1% of 1-wk and 4-wk diabetic hyperglycemic animals, respectively. The incidence of seizure was not 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-and 4-wk diabetic animals. In the CA1 and in the subicular regions of hippocampus, both diabetic hyperglycemic and normoglycemic animals showed 70-80% cell death. Diabetic hyperglycemic animals had more severe neuronal necrosis in the parietal cortex than normoglycemic animals. In diabetic hyperglycemic animals, neuronal damage involved additional brain structures, e.g., cingulate cortex, thalamus nuclei, substantia nigra, 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 diabetic hyperglycemic animals frequently develop postischemic seizures and that streptozotocin-induced hyperglycemia results exacerbated postischemic brain damage of the same density and distribution as in acutely glucose-infused animals.
authors.affiliation: Center for the Study of Neurological Disease, Queen's Neuroscience Institute, Queen's Medical Center, Honolulu, Hawaii 96813, USA.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: P A
authors.initials: PA
authors.lastname: Li
authors.forename: Q P
authors.initials: QP
authors.lastname: He
authors.forename: Y B
authors.initials: YB
authors.lastname: Ouyang
authors.forename: B K
authors.initials: BK
authors.lastname: Siesjö
mesh_terms: D000818:Animals; D001925:Brain Damage, Chronic / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology; D006943:Hyperglycemia / Q000473:pathology / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D019579:Neocortex / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000473:pathology; D013378:Substantia Nigra / Q000473:pathology; D013788:Thalamus / Q000473:pathology