Forced, not voluntary, exercise effectively induces neuroprotection in stroke

Katherine Hayes, Shane Sprague, Miao Guo, William Davis, Asher Friedman, Ashwini Kumar, David F. Jimenez, Yuchuan Ding

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


Previous treadmill exercise studies showing neuroprotective effects have raised questions as to whether exercise or the stress related to it may be key etiologic factors. In this study, we examined different exercise regimens (forced and voluntary exercise) and compared them with the effect of stress-only on stroke protection. Adult male Sprague-Dawley rats (n = 65) were randomly assigned to treatment groups for 3 weeks. These groups included control, treadmill exercise, voluntary running wheel exercise, restraint, and electric shock. Levels of the stress hormone, corticosterone, were measured in the different groups using ELISA. Animals from each group were then subjected to stroke induced by a 2-h middle cerebral artery (MCA) occlusion followed by 48-h reperfusion. Infarct volume was determined in each group, while changes in gene expression of stress-induced heat shock proteins (Hsp) 27 and 70 were compared using real-time PCR between voluntary and treadmill exercise groups. The level of corticosterone was significantly higher in both stress (P < 0.05) and treadmill exercise (P < 0.05) groups, but not in the voluntary exercise group. Infarct volume was significantly reduced (P < 0.01) following stroke in rats exercised on a treadmill. However, the amelioration of damage was not duplicated in voluntary exercise, even though running distance in the voluntary exercise group was significantly (P < 0.01) longer than that of the forced exercise group (4,828 vs. 900 m). Furthermore, rats in the electric shock group displayed a significantly increased (P < 0.01) infarct volume. Expression of both Hsp 27 and Hsp 70 mRNA was significantly increased (P < 0.01) in the treadmill exercise group as compared with that in the voluntary exercise group. These results suggest that exercise with a stressful component, rather than either voluntary exercise or stress alone, is better able to reduce infarct volume. This exercise-induced neuroprotection may be attributable to up-regulation of stress-induced heat shock proteins 27 and 70.

Original languageEnglish (US)
Pages (from-to)289-296
Number of pages8
JournalActa Neuropathologica
Issue number3
StatePublished - Mar 2008
Externally publishedYes


  • Hsp27
  • Hsp70
  • Ischemia/reperfusion
  • Running wheel
  • Stress
  • Treadmill
  • Voluntary

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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