The effects of melatonin supplementation on neurobehavioral outcomes and clinical severity in rodent models of multiple sclerosis; a systematic review and meta-analysis

Background Through the antioxidant and anti-inflammation pathways, melatonin is proposed as a safe and effective intervention in neurological diseases. This study aims to evaluate the effects of melatonin supplementation on the neurobehavioral and clinical outcomes in animal models of multiple sclerosis (MS). Methods This study was conducted following the PRISMA statement. Animal studies that reported the effects of melatonin in preclinical MS models, including the experimental autoimmune encephalomyelitis (EAE) and cuprizone model for demyelination are included in this study. A systematic search in PubMed, Web of Science, Embase, and Scopus up was conducted in April 2023. The collaborative Approach to Meta-Analysis and Review of Animal Experimental Studies (CAMARADES) critical appraisal tool was used for the quality assessment of the studies and the quantitative synthetizes were conducted using the comprehensive meta-analysis software. Results Out of 542 studies, finally 21 studies, including 14 studies in the EAE model and 7 studies of the toxic demyelination method with cuprizone were included. The route of administration was intraperitoneal in 18 studies, oral in 2 studies, and subcutaneous in 1 study. The quantitative synthesis of the EAE clinical severity scale was associated with significant differences (standardized mean difference [SDM]: − 2.52; − 3.61 to − 1.42; p value < 0.01). In subgroup analyses, the difference was statistically significant in the mouse subgroup (SMD: − 2.60; − 3.74 to − 1.46; p value < 0.01). Discussion This study encountered that melatonin may be associated with improved behavioral and cognitive outcomes of preclinical models of MS with acceptable safety profiles. Funding The research was supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71005).