Effect of Vitamin E on Cerebral Hypoxia-Ischemia in Neonatal Rats

PURPOSE: In order to evaluate the hypoxia-ischemia induced neurotoxic effect and the protective effect of vitamin E as an antioxidant, cell number and cell viability were measured in cerebral neurons and astrocytes derived in neonatal rats. METHODS: 7-day old neonatal rats were subjected to unilateral common carotid artery occlusion, and exposed to hypoxic condition for 3 hours. The protective effect of vitamin E, as an antioxidant was examined by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-(phenylami-nocarbonyl) 12H-tetrazolium hydroxide] assay and cell number on 14 days after hypoxia-ischemia when the rats received an intraperitoneal injection of vitamin E immediately following hypoxia-ischemia. RESULTS: Hypoxic-ischemic condition positively decreased the cell number and cell viability of rat cerebral neurons in a time-dependent manner when rats were killed 72 hours after hypoxia- ischemia. 72 hours after hypoxia-ischemia, the cell number and viability of astrocytes were slightly decreased, compared with the saline treated group. In rats treated with vitamin E, the cell number and cell viability of neurons were significantly increased compared with those of the saline- or non-treated group. In hypoxic-ischemic treated rats after 14 days from hypoxia- ischemia, astrocytes were significantly proliferated, but vitamin E showed the protective effect on hypoxic-ischemia induced cell proliferation and cell viability. CONCLUSION: It is suggested that hypoxic-ischemic condition is more toxic in neurons than astrocytes, and selective antioxidants such as vitamin E, especially when it was administered within two hours after hypoxia-ischemia, is highly effective in preventing the cell death of neurons and astrocytes from hypoxia-ischemic condition in neonatal rats.

Neurotoxic effect of 11?-dehydrocorticosterone on hippocampal neuron and its mechanism / 第二军医大学学报

Objective:To study the toxicity of 11 dehydrocorticosterone on hippocampal neurons and to determine whether 11? hydroxysteroid dehydrogenase (11? HSD1) is involved in the neurotoxity. Methods:Western blotting, radiometric enzyme activity assay and MTT assay were employed in this study. Results:Both 11? HSD1 protein and bioactivity were positive in the hippocampal neurons as demonstrated by Western blotting and radiometric enzyme activity assay. At concentration of 10 -6 mol/L, 11 dehydrocorticosterone was neurontoxic to hippocampal neurons cultured in serum free DMEM medium. This neurotoxic effect of 11 dehydrocorticosterone was blocked by 11? HSD1 inhibitor carbenoxolone (CBX) and glucocorticoid receptor (GR) antagonist RU38486, but not by mineralcocorticoid receptor (MR) antagonist spironolatone. Corticosterone and its derivative 11 dehydrocorticosterone up regulated 11? HSD1 level. Conclusion:11 dehydrocorticosterone has toxicity on hippocampal neurons, and it can be blocked by CBX, suggesting 11? HSD1 may convert biologically inactive 11 dehydrocorticosterone to active corticosterone. The up regulation of 11? HSD1 by glucocorticoids in return exaggerates the neurotoxic effect of corticosterone, which may play a positive role in the delayed neuron death during stress.