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Melatonin combined with exercise cannot alleviate cerebral injury in a rat model of focal cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2012年第13期7卷 993-999页

作者： Seunghoon Lee jinhee shin Minkyung Lee Yunkyung Hong Sang-Kil Lee Youngjeon Lee Tserentogtokh Lkhagvasuren Dong-Wook Kim Young-Ae Yang Kyu-Tae Chang Yonggeun Hong Department of Rehabilitation Science in Interdisciplinary Ph.D.Program Inje UniversityGimhae 621-749Republic of Korea Cardiovascular & Metabolic Disease Center College of Biomedical Science & EngineeringGimhae 621-749Republic of Korea Department of Smart Foods & Drugs School of Food & Life SciencesInje UniversityGimhae 621-749Republic of Korea Department of Pharmaceutical Engineering College of EngineeringInje UniversityGimhae 621-749Republic of Korea National Primate Research Center Korea Research Institute of BiotechnologyOchang 363-883Republic of Korea

Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also alleviate ischemic brain damage. In this study, adult rats were subjected to right middle cerebral artery occlusion after receiving 10 mg/kg melatonin or vehicle subcutaneously twice daily for 14 days. Forced exercise using an animal treadmill was performed at 20 m/min for 30 minutes per day for 6 days prior to middle cerebral artery occlusion. After middle cerebral artery occlusion, each rat received melatonin combined with exercise, melatonin or exercise alone equally for 7 days until sacrifice. Interestingly, rats receiving melatonin combined with exercise exhibited more severe neurological deficits than those receiving melatonin or exercise alone. Hypoxia-inducible factor la mRNA in the brain tissue was upregulated in rats receiving melatonin combined with exercise. Similarly, microtubule associated protein-2 mRNA expression was significantly upregulated in rats receiving melatonin alone. Chondroitin sulfate proteoglycan 4 （NG2） mRNA expression was significantly decreased in rats receiving melatonin combined with exercise as well as in rats receiving exercise alone. Furthermore, neural cell loss in the primary motor cortex was significantly reduced in rats receiving melatonin or exercise alone, but the change was not observed in rats receiving melatonin combined with exercise. These findings suggest that excessive intervention with melatonin, exercise or their combination may lead to negative effects on ischemia/reperfusion-induced brain damage.

关键词： wfocal cerebral ischemiaJreperfusion melatonin exercise neurological function brain tissue loss microtubule associated protein-2 chondroitin sulfate proteoglycan 4 NG2 hypoxia-inducible factor1 alpha neural regeneration

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