EFFECTS OF RECOMBINANT SUPEROXIDE-DISMUTASE ON MANGANESE SUPEROXIDE-DISMUTASE GENE-EXPRESSION IN GERBIL HIPPOCAMPUS AFTER ISCHEMIA

Background and Purpose We reported that recombinant human superoxide d ismutase ameliorates delayed neuronal death in the postischemic gerbil hippocampus. Since postischemic induction of copper-zinc superoxide d ismutase messenger RNA was abolished by this treatment, oxygen radical s generated on reperfusion may induce the expression of this gene. In the present study we examined whether oxygen radicals also induce the expression of manganese superoxide dismutase messenger RNA in the post ischemic brain. Methods We induced transient cerebral ischemia by occl uding the bilateral common carotid arteries of gerbils. Recombinant hu man superoxide dismutase (8x10(5) U/kg) or apo-superoxide dismutase wa s administered intravenously 1 minute before a 5-minute occlusion of t he carotid arteries. We analyzed both copper-zinc and manganese supero xide dismutase RNA by in situ hybridization histochemistry and by Nort hern and dot blot analyses using radioisotope-labeled oligonucleotide probes. Results Hybridization with the manganese superoxide dismutase messenger RNA occurred at the limit of detection in normal CA1 neurons . We observed striking increases in the labeling of CA1 up to 24 hours after 5 minutes of ischemia. The hybridization occurred anew in glial cells of the CA1 layer during 3 to 7 days. Pretreatment with recombin ant human superoxide dismutase had no effect on the postischemic induc tion of manganese superoxide dismutase messenger RNA, whereas the same treatment significantly attenuated (P<.01) the increase in copper-zin c superoxide dismutase messenger RNA. Conclusions Our results demonstr ated temporal postischemic induction of manganese superoxide dismutase messenger RNA. The inducer may not be superoxide radicals but may be other chemical mediators such as cytokines.