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The effect of rapamycin treatment on cerebral ischemia: A systematic review and meta-analysis of animal model studies
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 2018 World Stroke Organization
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 Type:||Refereed Article|
|Keywords:||stroke, rapamycin, mtor, neuroprotection, blood flow|
|Research Division:||Biomedical and Clinical Sciences|
|Research Field:||Neurology and neuromuscular diseases|
|Objective Division:||Expanding Knowledge|
|Objective Group:||Expanding knowledge|
|Objective Field:||Expanding knowledge in the biomedical and clinical sciences|
|UTAS Author:||Howells, DW (Professor David Howells)|
|UTAS Author:||Sutherland, BA (Associate Professor Brad Sutherland)|
|Funding Support:||National Health and Medical Research Council (APP1137776)|
|Web of Science® Times Cited:||17|
|Downloads:||42 View Download Statistics|
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