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Early Exercise Protects the Blood-Brain Barrier from Ischemic Brain Injury via the Regulation of MMP-9 and Occludin in Rats
Department of Rehabilitation of Huashan Hospital, Fudan University, Shanghai 200040, China
State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 3 April 2013; in revised form: 5 May 2013 / Accepted: 16 May 2013 / Published: 24 May 2013
Abstract: Early exercise within 24 h after stroke can reduce neurological deficits after ischemic brain injury. However, the mechanisms underlying this neuroprotection remain poorly understood. Ischemic brain injury disrupts the blood-brain barrier (BBB) and then triggers a cascade of events, leading to secondary brain injury and poor long-term outcomes. This study verified the hypothesis that early exercise protected the BBB after ischemia. Adult rats were randomly assigned to sham, early exercise (EE) or non-exercise (NE) groups. The EE and NE groups were subjected to ischemia induced by middle cerebral artery occlusion (MCAO). The EE group ran on a treadmill beginning 24 h after ischemia, 30 min per day for three days. After three-days’ exercise, EB extravasation and electron microscopy were used to evaluate the integrity of the BBB. Neurological deficits, cerebral infarct volume and the expression of MMP-9, the tissue inhibitors of metalloproteinase-1 (TIMP-1), and occludin were determined. The data indicated that early exercise significantly inhibited the ischemia-induced reduction of occludin, and an increase in MMP-9 promoted TIMP-1 expression (p < 0.01), attenuated the BBB disruption (p < 0.05) and neurological deficits (p < 0.01) and diminished the infarct volume (p < 0.01). Our results suggest that the neuroprotection conferred by early exercise was likely achieved by improving the function of the BBB via the regulation of MMP-9 and occludin.
Keywords: early exercise; cerebral ischemia and reperfusion; blood brain barrier; MMP-9; occludin
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Zhang, Y.; Zhang, P.; Shen, X.; Tian, S.; Wu, Y.; Zhu, Y.; Jia, J.; Wu, J.; Hu, Y. Early Exercise Protects the Blood-Brain Barrier from Ischemic Brain Injury via the Regulation of MMP-9 and Occludin in Rats. Int. J. Mol. Sci. 2013, 14, 11096-11112.
Zhang Y, Zhang P, Shen X, Tian S, Wu Y, Zhu Y, Jia J, Wu J, Hu Y. Early Exercise Protects the Blood-Brain Barrier from Ischemic Brain Injury via the Regulation of MMP-9 and Occludin in Rats. International Journal of Molecular Sciences. 2013; 14(6):11096-11112.
Zhang, Yuling; Zhang, Pengyue; Shen, Xiafeng; Tian, Shan; Wu, Yi; Zhu, Yulian; Jia, Jie; Wu, Junfa; Hu, Yongshan. 2013. "Early Exercise Protects the Blood-Brain Barrier from Ischemic Brain Injury via the Regulation of MMP-9 and Occludin in Rats." Int. J. Mol. Sci. 14, no. 6: 11096-11112.