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Title: Treadmill pre-training ameliorates brain edema in ischemic stroke via down-regulation of aquaporin-4 : an MRI study in rats
Authors: He, Z
Wang, X
Wu, Y
Jia, J
Hu, Y
Yang, X
Li, J
Fan, M
Zhang, L
Guo, J
Leung MCP 
Issue Date: 2014
Publisher: Public Library of Science
Source: PLoS one, 2014, v. 9, no. 1, e84602, p. 1-11 How to cite?
Journal: PLoS one 
Abstract: Objective: Treadmill 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.
Methods: Transient middle cerebral artery occlusion to induce stroke was performed on rats after 2 weeks of treadmill pretraining. 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.
Results: Treadmill 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.
Conclusions: Treadmill pre-training may reduce cerebral edema and BBB dysfunction during cerebral ischemia/reperfusion injury via the down-regulation of AQP4.
EISSN: 1932-6203
DOI: 10.1371/journal.pone.0084602
Rights: © 2014 He et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The following publication He, Z., Wang, X., Wu, Y., Jia, J., Hu, Y., Yang, X., . . . Leung, M. C. P. (2014). Treadmill pre-training ameliorates brain edema in ischemic stroke via down-regulation of aquaporin-4: An MRI study in rats. PLoS ONE, 9(1), e84602, 1-11 is available at
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