碩士 / 國立陽明大學 / 生理學研究所 / 90 / Kainic acid (KA、kainate) is a structural analog of glutamate. It is well known that both systemic and intracerebral administrations of KA induce persistent seizures and seizure-mediated brain damage via a selective degeneration of neurons, especially in hippocampal area. One of the possible mechanisms underlying KA-induced neurotoxicity is via oxidative stress. Hypoxic pretreatment (HP) has been reported to reduce oxidative injuries in heart, kidney and brain. In the present study, the neuroprotective effect of HP on KA-induced neurotoxicity was investigated. HP was performed by placing female Wistar rats (weighing 200 to 250g) in an altitude chamber at 5500m (380mmHg) for 15 hours/day for 4 weeks. The age-matched rats under normoxic condition (760mmHg) were used as controls. Our salicylate-trapping study showed that KA induced hydroxyl radical formation in normoxic rats and HP attenuated KA-induced hydroxyl radical formation In chronic experiments, KA (0.6、0.2、0.06μg/5μl) was locally infused in hippocampus of chloral hydrate-anesthetized rats. Seven days after the infusion, KA increased lipid peroxidation in the infused hippocampus in normoxic rats. HP attenuated KA-induced lipid peroxidation. Moreover, HP decreased KA-induced hippocampal CA3 neuronal death. In the neurotransmitter study, KA did not change NE and 5-HT contents but increased 5-HIAA content in the infused hippocampus in normoxic rats. HP did not alter basal NE, 5-HT but increased 5-HIAA content. Furthermore, HP potentiated KA-induced increase in 5-HIAA. In GSH/GSSG system, KA depleted GSH content and decreased GSH/GSSG ratio in the infused hippocampus. HP attenuated the KA-induced reductions in GSH content and GSH/GSSG ratio. In antioxidative defensive enzyme system, KA decreased superoxide dismutase (SOD) activity, increased glutathione peroxidase (GPx) and had no effect on catalase activity in the infused hippocampus of normoxic group. A 4-wk hypoxic pretreatment prevented KA-induced increase in GPx and did not alter catalase activity. HP actually attenuated KA-induced reduction in SOD activity. Our results showed that local application of KA-induced oxidative injuries in rat hippocampus. Furthermore, HP prevented KA-induced neurotoxicity in rat hippocampus via up-regulation of antioxidative defense mechanisms.
| Identifer | oai:union.ndltd.org:TW/090YM000116009 |
| Date | January 2002 |
| Creators | Cheng-Hao Wang, 王證豪 |
| Contributors | Tsai-Hsien Chiu, Anya Maan-Yuh Lin, 邱蔡賢, 林滿玉 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 80 |
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