Melatonin combined with exercise cannot alleviate cerebral injury in a rat model of focal cerebral ischemia/reperfusion injury.
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 1α 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.
Department of Rehabilitation Science in Interdisciplinary Ph.D. Program, Inje University, Gimhae 621-749, Republic of Korea.
Seunghoon
S
Lee
Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Gimhae 621-749, Republic of Korea.
Jinhee
J
Shin
Department of Rehabilitation Science in Interdisciplinary Ph.D. Program, Inje University, Gimhae 621-749, Republic of Korea.
Minkyung
M
Lee
Department of Rehabilitation Science in Interdisciplinary Ph.D. Program, Inje University, Gimhae 621-749, Republic of Korea.
Yunkyung
Y
Hong
Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Gimhae 621-749, Republic of Korea.
Sang-Kil
SK
Lee
Department of Rehabilitation Science in Interdisciplinary Ph.D. Program, Inje University, Gimhae 621-749, Republic of Korea.
Youngjeon
Y
Lee
Department of Smart Foods & Drugs, School of Food & Life Sciences, Inje University, Gimhae 621-749, Republic of Korea.
Tserentogtokh
T
Lkhagvasuren
Department of Pharmaceutical Engineering, College of Engineering, Inje University, Gimhae 621-749, Republic of Korea.
Dong-Wook
DW
Kim
Department of Rehabilitation Science in Interdisciplinary Ph.D. Program, Inje University, Gimhae 621-749, Republic of Korea.
Young-Ae
YA
Yang
National Primate Research Center, Korea Research Institute of Biotechnology, Ochang 363-883, Republic of Korea.
Kyu-Tae
KT
Chang
Department of Rehabilitation Science in Interdisciplinary Ph.D. Program, Inje University, Gimhae 621-749, Republic of Korea ; Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Gimhae 621-749, Republic of Korea ; National Primate Research Center, Korea Research Institute of Biotechnology, Ochang 363-883, Republic of Korea.
Yonggeun
Y
Hong
NG2; brain tissue loss; chondroitin sulfate proteoglycan 4; exercise; focal cerebral ischemia/reperfusion; hypoxia-inducible factor 1 alpha; melatonin; microtubule associated protein-2; neural regeneration; neurological function