Leptin-induced neuroprotection in ischemic stroke: a comprehensive systematic review and meta-analysis elucidating...

This systematic review and meta-analysis critically evaluates preclinical evidence on leptin's efficacy and mechanistic actions in rodent models of focal cerebral ischemia.

Comprehensive searches of PubMed, EMBASE, Scopus, and Google Scholar (1995-2024) identified 17 eligible studies (n = 1,383 animals), following PRISMA 2020 guidelines and PROSPERO registration (CRD42023461569). Data extraction and risk of bias assessment (SYRCLE tool) were conducted independently by dual reviewers. Pooled standardized mean differences (SMD) were calculated using a random-effects model.

Leptin administration significantly reduced infarct volume (SMD = -2.76; 95% CI: -3.65 to -1.86; p < 0.001) and ameliorated neurological deficits (SMD = -4.37; 95% CI: -5.80 to -2.95; p < 0.001), with pronounced effects in murine models. Mechanistically, leptin mitigated apoptosis - indicated by lowered cleaved Caspase-3 and TUNEL-positive cells - and promoted the upregulation of proteins involved in neuroprotection, including BCL-2, p-STAT, TRPV1, and the leptin receptor.

Although this meta-analysis demonstrates the promising neuroprotective properties of leptin, the substantial heterogeneity among studies and the resulting lower certainty of evidence highlight the critical need for future research employing standardized methodologies, rigorous study designs, and sufficient statistical power to validate these findings and support their translation into clinical settings.