Efficacy of bumetanide in animal models of ischemic stroke: a systematic review and meta-analysis

Abstract

This meta-analysis aimed to describe the efficacy of bumetanide in improving infarct volume, brain edema, and behavioral outcomes in animal models of cerebral ischemia. Embase, PubMed and Web of Science databases were searched from their inception to February 2024 (INPLASY:202430023). Data on the animal species, stroke model, drug dose, time of treatment, method of administration, study quality, and outcomes were extracted and pooled in a meta-analysis. The combined standardized mean difference (SMD) or mean difference (MD) estimates and 95% confidence intervals (CIs) were calculated using random-or fixed-effects models. Thirteen eligible studies involving >200 animals fulfilled the inclusion criteria and were included in this metaanalysis. Meta-analyses demonstrated that bumetanide treatment significantly reduced cerebral infarct volume (SMD: −0.42; 95% CI: −0.75, −0.09; p < 0.01; n = 186 animals) and consistently relieved brain edema (SMD: −1.39; 95% CI: −2.06, −0.72; p < 0.01; n = 64 animals). Subgroup analyses demonstrated that bumetanide treatment reduced infarct volume in transient but not permanent cerebral ischemia models. When administered after the stroke, it was more effective than treatment initiation before the stroke. Eight studies assessed the effect of bumetanide on behavioral function and the results showed that bumetanide treatment significantly improved neurobehavioral deficits (SMD: −2.35; 95% CI: −2.72, −1.97; p < 0.01; n = 250 animals). We conclude that bumetanide appears to be effective in reducing infarct volume and brain edema and improving behavioral recovery in animal models of cerebral ischemia. This mechanism needs to be confirmed through further investigation.