%0 Journal Article
%T The effect of rapamycin treatment on cerebral ischemia: A systematic review and meta
%A Alastair M Buchan
%A Brad A Sutherland
%A Daniel J Beard
%A David W Howells
%A Gina Hadley
%A Neal Thurley
%J International Journal of Stroke
%@ 1747-4949
%D 2019
%R 10.1177/1747493018816503
%X 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. To conduct a systematic review and meta-analysis evaluating the effectiveness of rapamycin in reducing infarct volume in animal models of ischemic stroke. 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%¨C35.7% p£¿<£¿0.01) improvement in infarct volume and 30.5% (95% CI 17.2%¨C43.8%, p£¿<£¿0.0001) improvement in neuroscores. Effect sizes were greatest in studies using lower doses of rapamycin. 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
%K Experimental stroke
%K infarct volume
%K mTOR
%K rapamycin
%K systematic review
%K meta-analysis
%U https://journals.sagepub.com/doi/full/10.1177/1747493018816503