title: Influence of oxidative stress on induced tolerance to ischemia in gerbil hippocampal neurons.
abstract: We investigated whether reversible oxidative stress induced by the administration of the superoxide dismutase inhibitor, diethyldithiocarbamate, could induce tolerance to subsequent cerebral ischemia in gerbil hippocampal neurons. Mature male gerbils received intraperitoneal injections of diethyldithiocarbamate (1.0 g/kg), which led to reduced superoxide dismutase activity and increases in thiobarbituric acid-reactive substance in the brain. Cerebral ischemia was produced by occluding the bilateral common carotid arteries for 5 min, either 2 or 4 days after diethyldithiocarbamate injection. One week after ischemia, samples from each brain were stained with hematoxylin-eosin to evaluate ischemic neuronal damage in the hippocampal CA1 sector. Diethyldithiocarbamate treatment 4 days before ischemia had significant protective effects against cerebral ischemia, while diethyldithiocarbamate 2-day pretreatment and vehicle treatment failed to show neuroprotection. Biochemical examinations showed a clear induction of heat shock protein 72 and a significant increase in manganese-containing superoxide dismutase in the hippocampus in animals treated with diethyldithiocarbamate 4 days prior to ischemia. These results suggested that the oxidative stress caused by diethyldithiocarbamate could induced tolerance to ischemia in the gerbil brain, and that the increase in the biosynthesis of manganese-containing superoxide dismutase and heat shock protein 72 could provide a biochemical explanation of the tolerance induced under these conditions.
authors.affiliation: First Department of Internal Medicine, Osaka University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohtsuki
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Kuwabara
authors.forename: K
authors.initials: K
authors.lastname: Kitagawa
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Taniguchi
authors.forename: T
authors.initials: T
authors.lastname: Kamada
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004050:Ditiocarb / Q000494:pharmacology; D005609:Free Radicals; D005849:Gerbillinae; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000502:physiology*; D006624:Hippocampus / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D005609:Free Radicals; D006360:Heat-Shock Proteins; D004050:Ditiocarb; D013482:Superoxide Dismutase