| Inhibitory Effect of Melatonin on Kainic Acid-Induced Hippocampal Neuronal Injury. |
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Seung Yun Chung, Seol Heui Han, Jae Kyun Hu, Young Hoon Kim, In Goo Lee, Kyung Tai Whang |
1Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
2Depatment of Neurology, Chungbuk National University Hospital, Chungbuk, Korea. |
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| Abstract |
PURPOSE
It has been suggested that the pineal hormone melatonin(MEL) protects neurons in vitro from excitotoxicity mediated by kainate-sensitive glutamate receptors and from oxidative stress-induced DNA damage and apoptosis. The present study evaluated the antioxidatives and anti-inflammatory effect of melatonin on kainic acid(KA)-induced neuronal injury in the hippocampus in vivo. METHODS: 30 adult male Sprague-Dawley rats were divided into two equal groups. Control group was treated with KA only and test group was treated with KA and MEL. We injected 10 mg/kg KA intraperitoneal into rats. This results in selective neuronal injury accompanied by intense microglial activation and triggers DNA damage in the hippocampus. We tested the in vivo efficacy of MEL in preventing KA-induced neuronal injury and neuroinflammation in the hippocampus. MEL(2.5 mg/kg) was injected i.p. four times : 20 min before KA, immidiately after, and 1 and 2 h after the KA. Rats were sacrificed 72 h later and their hippocampi were examined for evidence of DNA damage (in situ dUTP-end-labeling, i.e. TUNEL staining), cell viability(H&E staining), microglial (isolectin-B4 histochemistry), astroglial responses(glial fibrillary acidic protein, GFAP immunohistochemistry), and lipid peroxidation(4-hydroxynonenal immunohistochemistry). RESULTS: The cumulative dose of 10 mg/kg MEL attenuates KA-induced neuronal death as well as microglial activation and lessens DNA breaks. CONCLUSION: A possible mechanism of MEL-provided neuroprotection lies in its antioxidant and anti-inflammatory action. Present data suggest that MEL holds potential for the treatment of acute brain pathologies such as epilepsy-associated brain damage, stroke, and brain trauma. |
| Key Words:
Epilepsy, Melatonin, Kainic Acid, Hippocampus, Neuronal injury |
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