Exercise reduces infarct volume and facilitates neurobehavioral recovery: results from a systematic review and meta-analysis of exercise in experimental models of focal ischemia

Kieren J. Egan, Heidi Janssen, Emily S. Sena, Lesa Longley, Sally Speare, David W. Howells, Neil J. Spratt, Malcolm R. Macleod, Gillian E. Mead*, Julie Bernhardt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Background. Regular exercise reduces the risk of a first-ever stroke and is associated with smaller infarcts. Although evidence has suggested that therapeutic exercise following stroke is beneficial, we do not yet know whether exercise reduces stroke severity and improves functional recovery. The mechanisms underlying any benefit remain unclear.

Objective. To conduct a systematic review and meta-analysis of studies testing exercise in animal models of ischemic stroke where outcomes were measured as infarct volume, neurobehavioral score, neurogenesis, or a combination of these. We also sought evidence of publication bias.

Methods. We searched 3 online databases for publications reporting the use of exercise in focal cerebral ischemia. We used DerSimonian and Laird normalized random-effects meta-analysis and meta-regression to determine the impact of study quality and design on the efficacy of exercise.

Results. Overall, exercise reduced infarct volume by 25.2% (95% confidence interval [CI] = 19.0%-31.3%; 65 experiments and 986 animals) and improved neurobehavioral score by 38.2% (95% CI = 29.1%-47.3%; 42 experiments; n = 771). For both outcomes, larger effects were seen when exercise preceded ischemia rather than came after it. For neurobehavioral scores, we found evidence of publication bias. Reported study quality was moderate (median score 5/10). Both model-specific (eg, type of ischemia) and exercise-specific characteristics influenced reported outcome.

Conclusion. Exercise, either before or after ischemia, reduced infarct volume and improved neurobehavioral score. However, overall estimates of efficacy were higher in studies at risk of bias, and for neurobehavioral outcomes, there was evidence of a substantial publication bias.

Original languageEnglish
Pages (from-to)800-812
Number of pages13
JournalNeurorehabilitation and Neural Repair
Volume28
Issue number8
DOIs
Publication statusPublished - 1 Jan 2014

Funding

Exercise improves outcome in animal models of stroke. Reported study quality was good, but there was evidence of publication bias. The most effective intensity and timing of and motivational drive for exercise might usefully be addressed in future well-conducted animal studies. Authors’ Note KJE and HJ contributed equally to this work. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: KE and MM are supported by the MRC Trials Methodology Hub. NS was supported by an Australian NHMRC career development fellowship (APP1035465). HJ was supported by a Postgraduate Scholarship from the National Heart Foundation, Australia and the Emlyn and Jennie Thomas Post Graduate Medical Research Scholarship. LL was supported by a PhD studentship from The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704). Funding from the Biotechnology and Biological Sciences Research Council (BBSRC), Engineering and Physical Sciences Research Council (EPSRC), Economic and Social Research Council (ESRC), and Medical Research Council (MRC) is gratefully acknowledged.

Keywords

  • exercise
  • exercise preconditioning
  • focal ischemia
  • meta-analysis
  • stroke
  • systematic review

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