Protective effect and possible mechanisms of resveratrol in animal models of spinal cord injury: a preclinical systematic review and meta-analysis

Background Resveratrol has shown potential neuroprotective effects in experimental spinal cord injury (SCI), but its overall efficacy has not been systematically evaluated. This study aimed to assess the effects of resveratrol on locomotor recovery and related pathological and biochemical outcomes in animal models of SCI. Methods A systematic review and meta-analysis was conducted on controlled in vivo studies of resveratrol in experimentally induced SCI models, including traumatic and ischemia-reperfusion models. Major locomotor, oxidative stress, inflammatory, apoptotic, and edema-related outcomes were pooled as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results In total, 38 studies were included. Resveratrol significantly improved locomotor recovery, as reflected by higher BBB scores at 3, 7, 14, 21, and 28 days after injury (SMDs ranging from 2.56 to 5.23) and higher BMS scores at the corresponding time points (SMDs ranging from 1.40 to 3.37). It also attenuated oxidative stress, with reduced MDA levels at 24 h, 3 days, and 7 days, and increased SOD and GSH levels. Inflammatory responses were suppressed, as shown by lower MPO, TNF-α, IL-1β, and IL-6 levels, while IL-10 showed a borderline increase at 7 days. In addition, resveratrol reduced the TUNEL-positive rate and spinal cord water content, suggesting a possible reduction in apoptotic cell death and a potential effect on spinal cord edema based on spinal cord water content. However, apoptosis-related molecular markers showed heterogeneous results, with no significant changes in BCL-2 and caspase-3 at some time points and an increased BAX level at 7 days. Conclusions Current preclinical evidence supports that resveratrol exerts neuroprotective effects in SCI animal models by improving locomotor recovery and modulating oxidative stress, inflammation, apoptosis-related changes, and edema, although molecular evidence for apoptosis-related pathways remains heterogeneous. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420261289830.