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Exercise Rehabilitation Attenuates Cognitive Deficits in Rats with Traumatic Brain Injury by Stimulating the Cerebral HSP20/BDNF/TrkB Signalling Axis

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Abstract

Physical exercise (PE) is an effective method for improving cognitive function among patients with traumatic brain injury (TBI). We previously demonstrated that PE with an infrared-sensing running wheel (ISRW) system provides strong neuroprotection in an experimental animal model of stroke. In this study, we used fluid percussion injury in rats to simulate mild TBI. For rats, we used both passive avoidance learning and the Y-maze tests to evaluate cognitive function. We investigated whether PE rehabilitation attenuated cognitive deficits in rats with TBI and determined the contribution of hippocampal and cortical expression of heat shock protein 20 (HSP20) to PE-mediated cognitive recovery. In addition to increasing hippocampal and cortical expression of HSP20, brain-derived neurotrophic factor (BDNF), and the tropomyosin receptor kinase B (TrkB) ratio, PE rehabilitation significantly attenuated brain contusion and improved cognitive deficits in the rat model. Furthermore, reducing hippocampal and cortical expression of HSP20 with an intracerebral injection of pSUPER hsp20 small interfering RNA significantly diminished the PE-induced overexpression of hippocampal and cortical BDNF and the TrkB ratio and also reversed the beneficial effect of PE in reducing neurotrauma and the cognitive deficits. A positive Pearson correlation was found between HSP20 and BDNF, as well as between HSP20 and TrkB, in the hippocampal and cortical tissues. We thus conclude that post-ischaemic ISRW exercise rehabilitation attenuates cognitive deficits, as well as brain contusions, in TBI rats by stimulating the cerebral HSP20/BDNF/TrkB signalling axis.

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Funding

This work was supported by the Ministry of Science and Technology (Taiwan) grants MOST 104-2314-B-384-003-MY3 (to C.C. Chio), MOST 106-2314-B-384-001-MY3 (to C.C. Chio), and Chi Mei Medical Center (Taiwan) grant CMFHT 10504 (to C.P. Chang).

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Authors and Affiliations

  1. Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, Tainan, 710, Taiwan

    Willy Chou

  2. Department of Recreation and Healthcare Management, Chia Nan University of Pharmacy and Science, Tainan, 71710, Taiwan

    Willy Chou

  3. Department of Medical Research, Chi Mei Medical Center, Tainan, 710, Taiwan

    Yu-Fan Liu, Cheng-Hsien Lin, Mao-Tsun Lin, Wen-Pin Liu & Ching-Ping Chang

  4. Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, 305-8574, Ibaraki, Japan

    Yu-Fan Liu

  5. Department of Leisure, Recreation, and Tourism Management, Southern Taiwan University of Science and Technology, Tainan, 710, Taiwan

    Cheng-Hsien Lin

  6. Department of Electronic Engineering, National Chin-Yi University of Technology, Taichung, 41170, Taiwan

    Chi-Chun Chen

  7. Division of Neurosurgery, Department of Surgery, Chi Mei Medical Center, Tainan, 710, Taiwan

    Chung-Ching Chio

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  1. Willy Chou
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Correspondence to Ching-Ping Chang or Chung-Ching Chio.

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The Institutional Animal Care and Use Committee at Chi Mei Medical Center approved all experimental procedures (IACUC approved number 105110328).

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Chou, W., Liu, YF., Lin, CH. et al. Exercise Rehabilitation Attenuates Cognitive Deficits in Rats with Traumatic Brain Injury by Stimulating the Cerebral HSP20/BDNF/TrkB Signalling Axis. Mol Neurobiol 55, 8602–8611 (2018). https://doi.org/10.1007/s12035-018-1011-2

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