Treadmill Pre-Training Ameliorates Brain Edema in Ischemic Stroke via Down-Regulation of Aquaporin-4: An MRI Study in Rats |
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| Authors: | Zhijie He Xiaolou Wang Yi Wu Jie Jia Yongshan Hu Xiaojiao Yang Jianqi Li Mingxia Fan Li Zhang Jinchun Guo Mason C P Leung |
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| Institution: | 1. Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai, China.; 2. Shanghai Key Laboratory of Magnetic Resonance, Department of Physics, East China Normal University, Shanghai, China.; 3. State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China.; 4. Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, SAR, China.; National University of Singapore, Singapore, |
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| Abstract: | ObjectiveTreadmill pre-training can ameliorate blood brain barrier (BBB) dysfunction in ischemia-reperfusion injury, however, its role in ischemic brain edema remains unclear. This study assessed the neuroprotective effects induced by treadmill pre-training, particularly on brain edema in transient middle cerebral artery occluded model.MethodsTransient middle cerebral artery occlusion to induce stroke was performed on rats after 2 weeks of treadmill pre-training. Magnetic resonance imaging (MRI) was used to evaluate the dynamic impairment of cerebral edema after ischemia-reperfusion injury. In addition, measurements of wet and dry brain weight, Evans Blue assay and Garcia scores were performed to investigate the cerebral water content, BBB permeability and neurologic deficit, respectively. Moreover, during ischemia-reperfusion injury, the expression of Aquaporin 4 (AQP4) was detected using immunofluorescence and Western bloting analyses.ResultsTreadmill pre-training improved the relative apparent diffusion coefficient (rADC) loss in the ipsilateral cortex and striatum at 1 hour and 2.5 hours after cerebral ischemia. In the treadmill pre-training group, T2W1 values of the ipsilateral cortex and striatum increased less at 7.5 hours, 1 day, and 2 days after stroke while the brain water content decreased at 2 days after ischemia. Regarding the BBB permeability, the semi-quantitative amount of contrast agent leakage of treadmill pre-training group significantly decreased. Less Evans Blue exudation was also observed in treadmill pre-training group at 2 days after stroke. In addition, treadmill pre-training mitigated the Garcia score deficits at 2 days after stroke. Immunofluorescence staining and Western blotting results showed a significant decrease in the expression of AQP4 after treadmill ischemia following pre-training.ConclusionsTreadmill pre-training may reduce cerebral edema and BBB dysfunction during cerebral ischemia/reperfusion injury via the down-regulation of AQP4. |
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