Melatonin for Spinal Cord Injury in Animal Models: A Systematic Review and Network Meta-Analysis

Spinal cord injury (SCI) leads to loss of function below the lesion and affects individuals worldwide. An increasing number of experimental studies support the effectiveness of melatonin (MT) for SCI. Our objectives were to investigate neurological recovery and anti-oxidant effects of MT in animal models of SCI, and to explore the appropriate dose. Published MT studies in SCI animal models described in six databases were searched. Two practiced investigators selected the studies, extracted the data, and independently evaluated the quality of the included studies. A meta-analysis evaluated the effect of MT in SCI and a network meta-analysis was performed to explore the appropriate MT dose for SCI models. Thirteen studies were analyzed, of which three were high quality. The results of the meta-analysis manifested that the behavioral evaluation (Basso, Beattie, and Bresnahan scales, n=90, p=0.003; motor function scores, n=92, p=0.004; Tarlov's criteria, n=150, p=0.002; inclined plane test, n=150, p=0.001) and biochemical outcomes (malondialdehyde, n=121, p=0.0010; glutathione levels, n=64, p<0.0001; and myeloperoxidase activity, n=32, p<0.00001) were improved, compared with the control group, after MT administration. A dose of 12.5mg/kg was most effective in SCI rat models. Studies indicated that MT administration significantly improved neurological recuperation and anti-oxidant effects in rat models of SCI. The appropriate dose of MT was 12.5mg/kg for SCI rat models. The majority of included studies were low quality; however, optimal MT treatment in SCI still requires high quality studies.