Effect of Electrical Stimulation on Remyelination in Preclinical Models of Multiple Sclerosis: A Systematic Review

Different types of electrical stimulations (ES), transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), and peripheral nerve stimulation (PNS) have emerged as neuromodulatory treatments to promote remyelination in multiple sclerosis (MS). Although preclinical evidence continues to accumulate, a systematic review assessing the effect of ES on remyelination across MS-relevant models has not been undertaken.

PubMed-MEDLINE, Embase, and Scopus databases were systematically searched up to January 2026 for in vivo studies investigating ES in demyelinating animal models. Two reviewers independently extracted data on study design, stimulation parameters, and quantitative measures of myelin integrity, including visual evoked potential (VEP) latency, and histological myelin content outcomes. Risk of bias was assessed using SYRCLE's tool.

Six eligible studies met the inclusion criteria, comprising EAE, cuprizone, and lysolecithin lesion models. Across these studies, ES was associated with improvements in indices of remyelination, evidenced by reduced VEP latency, and increased myelin protein expression. Effects of tDCS depended on polarity and timing, with anodal stimulation supporting oligodendrocyte maturation during recovery and cathodal stimulation attenuating glial activation during inflammation. VNS promoted remyelination through anti-inflammatory and trophic signaling, and PNS supported spinal remyelination via peripheral to central neuroimmune modulation.

Limited but convergent preclinical evidence suggests ES may enhance remyelination by modulating neuronal and inflammatory pathways. However, standardized protocols of stimulation and multimodal imaging studies are needed for clinical translation in MS.