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The effect of rapamycin treatment on cerebral ischemia: A systematic review and meta-analysis of animal model studies

Citation

Beard, DJ and Hadley, G and Thurley, N and Howells, DW and Sutherland, BA and Buchan, AM, The effect of rapamycin treatment on cerebral ischemia: A systematic review and meta-analysis of animal model studies, International journal of stroke, 14, (2) pp. 137-145. ISSN 1747-4930 (2019) [Refereed Article]


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Copyright Statement

Copyright 2018 World Stroke Organization

DOI: doi:10.1177/1747493018816503

Abstract

Background: Amplifying endogenous neuroprotective mechanisms is a promising avenue for stroke therapy. One target is mammalian target of rapamycin (mTOR), a serine/threonine kinase regulating cell proliferation, cell survival, protein synthesis, and autophagy. Animal studies investigating the effect of rapamycin on mTOR inhibition following cerebral ischemia have shown conflicting results.

Aim: To conduct a systematic review and meta-analysis evaluating the effectiveness of rapamycin in reducing infarct volume in animal models of ischemic stroke.

Summary of review: Our search identified 328 publications. Seventeen publications met inclusion criteria (52 comparisons: 30 reported infarct size and 22 reported neurobehavioral score). Study quality was modest (median 4 of 9) with no evidence of publication bias. The point estimate for the effect of rapamycin was a 21.6% (95% CI, 7.6%35.7% p < 0.01) improvement in infarct volume and 30.5% (95% CI 17.2%43.8%, p < 0.0001) improvement in neuroscores. Effect sizes were greatest in studies using lower doses of rapamycin.

Conclusion: Low-dose rapamycin treatment may be an effective therapeutic option for stroke. Modest study quality means there is a potential risk of bias. We recommend further high-quality preclinical studies on rapamycin in stroke before progressing to clinical trials.

Item Details

Item Type:Refereed Article
Keywords:stroke, rapamycin, mtor, neuroprotection, blood flow
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurology and Neuromuscular Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cardiovascular System and Diseases
UTAS Author:Howells, DW (Professor David Howells)
UTAS Author:Sutherland, BA (Dr Brad Sutherland)
ID Code:131339
Year Published:2019
Funding Support:National Health and Medical Research Council (APP1137776)
Deposited By:Office of the School of Medicine
Deposited On:2019-03-13
Last Modified:2019-04-03
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