Neuroprotective effects of adiponectin in experimental models of ischemic stroke: A systematic review and meta-analysis

Adiponectin, a pleiotropic adipokine, exerts neuroprotective actions in ischemic stroke through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. This systematic review and meta-analysis synthesized preclinical evidence on the effects of adiponectin in experimental models of cerebral ischemia. A comprehensive search of PubMed, EMBASE, Scopus, and Google Scholar (1995–2024) identified rodent studies employing the middle cerebral artery occlusion (MCAO) model and reporting infarct volume or neurological outcomes. Following PRISMA 2020 guidelines and PROSPERO registration (CRD42023460289), two independent reviewers performed data extraction and risk-of-bias assessment. Eighteen eligible studies (n = 1,309 animals) demonstrated that adiponectin markedly reduced infarct volume (SMD = –3.18; 95% CI: –4.12 to –2.25; p < 0.001; I² = 86%) and improved neurological scores (SMD = –2.17; 95% CI: –2.84 to –1.51; p < 0.001; I² = 82%), indicating a reduction in ischemic injury. Molecular analyses revealed lower levels of apoptotic (cleaved caspase-3, BAX, TUNEL-positive cells), inflammatory (IL-1β, TNF-α), and oxidative stress markers (ROS, MDA, 8-OHdG), alongside increased expression of neuroprotective proteins (BCL-2, SOD, p-AMPK, BDNF, VEGF, eNOS). Collectively, preclinical evidence supports the neuroprotective potential of adiponectin against ischemic brain injury. Nevertheless, study heterogeneity and low-to-moderate certainty of evidence highlight the need for standardized, adequately powered animal studies before translation to clinical settings.