Effect and mechanisms of resveratrol in animal models of ischemic stroke: A systematic review and Bayesian meta-analysis

Resveratrol (RSV) holds promise as cerebroprotective treatment in cerebral ischemia. This systematic review aims to assess the effects and mechanisms of RSV in animal models of ischemic stroke. We searched Medline, Embase and Web of Science to identify 75 and 57 eligible rodent studies for qualitative and quantitative syntheses, respectively. Range of evidence met 10 of 13 STAIR criteria. Median (Q1, Q3) quality score was 7 (5, 8) on the CAMARADES 15-item checklist. Bayesian meta-analysis showed SMD estimates (95% CI) favoring RSV: infarct size (-1.72 [-2.03; -1.41]), edema size (-1.61 [-2.24; -0.98]), BBB impairment (-1.85 [-2.54; -1.19]), neurofunctional impairment (-1.60 [-1.92; -1.29]), and motor performance (1.39 [0.64; 2.08]); and less probably neuronal survival (0.63 [-1.40; 2.48]) and apoptosis (-0.96 [-2.87; 1.02]). Species (rat vs mouse) was associated to a larger benefit. Sensitivity analyses confirmed robustness of the estimates. Reduction of oxidative stress, inflammation, and apoptosis underlie these effects. Our results quantitatively state the beneficial effects of RSV on structural and functional outcomes in rodent stroke models, update the evidence on the mechanisms of action, and provide an exhaustive list of targeted signaling pathways. Current evidence highlights the need for conducting further high-quality preclinical research to better inform clinical research.