Investigating the neurological function and anti-inflammatory effects of resveratrol in small mammal spinal cord injury models: A systematic review and meta-analysis

Background: Spinal cord injury (SCI) produces serious neurological and medical problems. Resveratrol (RES), a natural polyphenol, possesses anti-inflammatory and antioxidant characteristics and has revealed neuroprotective ability in central nervous system diseases. This study investigated the therapeutic potential of RES in rat, mouse, and rabbit SCI models. Methods: Articles were identified from Medline, Embase, Scopus, and Web of Science until April 25, 2025. Studies evaluating RES with SCI models were included. Main results were locomotor function, inflammation, oxidative stress, apoptosis, and neuronal survival. Random-effects meta-analysis showed standardized mean differences (SMDs) and their p -values. SYRCLE’s risk of bias tool and I 2 statistic were used for study quality and heterogeneity, respectively. Results: Twenty-six studies were included. RES improved locomotor function (SMD = 3.41, p < 0.0001). RES was associated with anti-inflammatory signaling, including decreased tumor necrosis factor-alpha (SMD = −4.64, p < 0.0001), interleukin (IL)-6 (SMD = −3.19, p < 0.0001), and IL-1β (SMD = −4.10, p < 0.0001). RES was associated with antioxidant signaling, including increased superoxide dismutase (SMD = 4.74, p < 0.0001) and glutathione (SMD = 3.21, p < 0.0001) and decreased malondialdehyde (SMD = −2.41, p < 0.0001). RES had significant effects on apoptotic signaling, including increased B-cell Lymphoma 2 (Bcl-2) (SMD = 3.55, p < 0.0001) and decreased Bcl-2-associated X protein (Bax) (SMD = −3.71, p = 0.010), Bax/Bcl-2 ratio (SMD = −6.83, p < 0.0001), and cleaved caspase-3 (SMD = −4.39, p < 0.0001), and terminal deoxynucleotidyl transferase dUTP nick end labeling (SMD = −3.81, p < 0.0001). RES treatment was associated with improved neuronal survival markers, including Nissl (SMD = 3.39, p < 0.0001), neuronal nuclei (SMD = 2.00, p < 0.0001), and growth-associated protein 43 (SMD = 3.13, p < 0.0001). Conclusion: In preclinical SCI models, RES is a promising neuroprotective agent. This suggests that further research is warranted regarding the potential role of RES in SCI treatment.