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Pre-Ischemic Treadmill Training for Prevention of Ischemic Brain Injury via Regulation of Glutamate and Its Transporter GLT-1
Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China
State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China
Department of Sports Medicine and Rehabilitation, Medical College of Fudan University, Shanghai 200032, China
The Third Teaching Hospital of Xinxiang Medical University, Xinxiang 453003, China
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 10 May 2012; in revised form: 14 July 2012 / Accepted: 19 July 2012 / Published: 26 July 2012
Abstract: Pre-ischemic treadmill training exerts cerebral protection in the prevention of cerebral ischemia by alleviating neurotoxicity induced by excessive glutamate release following ischemic stroke. However, the underlying mechanism of this process remains unclear. Cerebral ischemia-reperfusion injury was observed in a rat model after 2 weeks of pre-ischemic treadmill training. Cerebrospinal fluid was collected using the microdialysis sampling method, and the concentration of glutamate was determined every 40 min from the beginning of ischemia to 4 h after reperfusion with high-performance liquid chromatography (HPLC)-fluorescence detection. At 3, 12, 24, and 48 h after ischemia, the expression of the glutamate transporter-1 (GLT-1) protein in brain tissues was determined by Western blot respectively. The effect of pre-ischemic treadmill training on glutamate concentration and GLT-1 expression after cerebral ischemia in rats along with changes in neurobehavioral score and cerebral infarct volume after 24 h ischemia yields critical information necessary to understand the protection mechanism exhibited by pre-ischemic treadmill training. The results demonstrated that pre-ischemic treadmill training up-regulates GLT-1 expression, decreases extracellular glutamate concentration, reduces cerebral infarct volume, and improves neurobehavioral score. Pre-ischemic treadmill training is likely to induce neuroprotection after cerebral ischemia by regulating GLT-1 expression, which results in re-uptake of excessive glutamate.
Keywords: glutamate; glutamate transporter-1 (GLT-1); pre-ischemic treadmill training; ischemia; neuroprotection
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Yang, X.; He, Z.; Zhang, Q.; Wu, Y.; Hu, Y.; Wang, X.; Li, M.; Wu, Z.; Guo, Z.; Guo, J.; Jia, J. Pre-Ischemic Treadmill Training for Prevention of Ischemic Brain Injury via Regulation of Glutamate and Its Transporter GLT-1. Int. J. Mol. Sci. 2012, 13, 9447-9459.
Yang X, He Z, Zhang Q, Wu Y, Hu Y, Wang X, Li M, Wu Z, Guo Z, Guo J, Jia J. Pre-Ischemic Treadmill Training for Prevention of Ischemic Brain Injury via Regulation of Glutamate and Its Transporter GLT-1. International Journal of Molecular Sciences. 2012; 13(8):9447-9459.
Yang, Xiaojiao; He, Zhijie; Zhang, Qi; Wu, Yi; Hu, Yongshan; Wang, Xiaolou; Li, Mingfen; Wu, Zhiyuan; Guo, Zhenzhen; Guo, Jingchun; Jia, Jie. 2012. "Pre-Ischemic Treadmill Training for Prevention of Ischemic Brain Injury via Regulation of Glutamate and Its Transporter GLT-1." Int. J. Mol. Sci. 13, no. 8: 9447-9459.