Multiple sclerosis (MS), the most common disabling neurologic disease in young adults, results in demyelination within the central nervous system, decrements in functional ability, and progressive accumulation of disability. Electrical stimulation of the vagus nerve (VNS) has been shown to provide clinical benefits for disorders including rheumatoid arthritis, epilepsy, depression, and Crohn’s disease. In this report, we demonstrate that VNS decreases both clinical symptoms and molecular pathology in a standard rat model of MS, experimental autoimmune encephalomyelitis. We further show that VNS modulates gene expression, including those encoding inflammatory mediators, inflammatory reflex components, and oligodendrocyte differentiation and myelin synthesis. These data indicate that VNS may be a promising approach to treat MS and possibly impact remyelination.

Multiple sclerosis (MS) is a demyelinating central nervous system (CNS) disorder that is associated with functional impairment and accruing disability. There are multiple U.S. Food and Drug Administration (FDA)-approved drugs that effectively dampen inflammation and slow disability progression. However, these agents do not work well for all patients and are associated with side effects that may limit their use. The vagus nerve (VN) provides a direct communication conduit between the CNS and the periphery, and modulation of the inflammatory reflex via electrical stimulation of the VN (VNS) shows efficacy in ameliorating pathology in several CNS and autoimmune disorders. We therefore investigated the impact of VNS in a rat experimental autoimmune encephalomyelitis (EAE) model of MS. In this study, VNS-mediated neuroimmune modulation is demonstrated to effectively decrease EAE disease severity and duration, infiltration of neutrophils and pathogenic lymphocytes, myelin damage, blood–brain barrier disruption, fibrinogen deposition, and proinflammatory microglial activation. VNS modulates expression of genes that are implicated in MS pathogenesis, as well as those encoding myelin proteins and transcription factors regulating new myelin synthesis. Together, these data indicate that neuroimmune modulation via VNS may be a promising approach to treat MS, that not only ameliorates symptoms but potentially also promotes myelin repair (remyelination).