Neuroprotective effect and possible mechanism of edaravone in rat models of spinal cord injury: a protocol for a systematic review and meta-analysis

Abstract Background: Spinal cord injury (SCI) is one of the most disabling and devastating neurological conditions, afflicting individuals and societies widely. Edaravone, a well-known synthetic ROS scavenger, is approved in the treatment of amyotrophic lateral sclerosis. In recent years, the role of edaravone in the treatment of SCI has been investigated in a growing number of studies. Methods: The systematic review will include the controlled studies evaluating the neurological roles of edaravone on experiment rat models following SCI. The primary outcome is the 21-point Basso, Beattie, and Bresnahan locomotor rating scale, and preservation of white matter areas and malondialdehyde will be employed as the secondary outcomes. Two researchers will search PubMed, Embase, Web of Science, Scopus and Cochrane Library from their inception date independently. Following study selection, data extraction, and assessment of methodological quality in the included studies using the SYRCLE’s RoB tool, data from eligible studies will be pooled and analyzed using random‑effects models with RevMan 5.3 software. In case of sufficient data, subgroup analyses with respect to species, age, sex, duration of intervention, dose or route of administration will be carried out to explore the factors modifying on BBB scores. For exploring the appropriate dose of edaravone, a network meta-analysis approach will be conducted based on the Bayesian method. Importantly, the proposed mechanisms and changes of related molecules will be also extracted from included studies for comprehensively investigating the neuroprotective mechanism behind edaravone. Discussion: In this study, we will quantitatively analyze the role of edaravone in locomotor recovery and tissue damage in SCI rat model. Besides, the efficacy of edaravone in distinct scenarios will be investigated by subgroups, and we plan to predict the candidate dose that exerts the greater neuroprotective effect with network meta-analyses. Moreover, we will provide comprehensive overview on the mechanisms underlying the emerging neuroprotective effects of edaravone in SCI. This study will provide implications for future preclinical studies and clinical applications of SCI.