Molecular Neurobiology

, Volume 55, Issue 11, pp 8602–8611 | Cite as

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

  • Willy Chou
  • Yu-Fan Liu
  • Cheng-Hsien Lin
  • Mao-Tsun Lin
  • Chi-Chun Chen
  • Wen-Pin Liu
  • Ching-Ping Chang
  • Chung-Ching Chio


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.


Physical exercise Traumatic brain injury Heat shock protein 20 Brain-derived neurotrophic factor 


Funding Information

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).

Compliance with Ethical Standards

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

Conflict of Interest

The authors declare that they have no competing interests.

Supplementary material

12035_2018_1011_MOESM1_ESM.pdf (204 kb)
ESM 1 (PDF 204 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018
corrected publication April/2018

Authors and Affiliations

  1. 1.Department of Physical Medicine and RehabilitationChi Mei Medical CenterTainanTaiwan
  2. 2.Department of Recreation and Healthcare ManagementChia Nan University of Pharmacy and ScienceTainanTaiwan
  3. 3.Department of Medical ResearchChi Mei Medical CenterTainanTaiwan
  4. 4.Faculty of Health and Sport SciencesUniversity of TsukubaTsukubaJapan
  5. 5.Department of Leisure, Recreation, and Tourism ManagementSouthern Taiwan University of Science and TechnologyTainanTaiwan
  6. 6.Department of Electronic EngineeringNational Chin-Yi University of TechnologyTaichungTaiwan
  7. 7.Division of Neurosurgery, Department of SurgeryChi Mei Medical CenterTainanTaiwan

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