Journal
INTERNATIONAL JOURNAL OF STROKE
Volume 14, Issue 2, Pages 137-145Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1747493018816503
Keywords
Experimental stroke; infarct volume; mTOR; rapamycin; systematic review; meta-analysis
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Funding
- National Health and Medical Research Council [APP1137776]
- Rebecca L Cooper Foundation
- J J Mason and H S Williams Memorial Foundation
- Brain Foundation
- Royal Hobart Hospital Research Foundation
- Oxford University Clinical Academic Graduate School, Oxford
- MRC [MR/M022757/1] Funding Source: UKRI
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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.
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