Electrical stimulation of the vagus nerve ameliorates inflammation and disease activity in a rat EAE model of multiple sclerosis

• 成果类型: Article
• 署名作者: Natarajan, Chandramohan; Le, Linh H. D.; Gunasekaran, Manojkumar; Tracey, Kevin J.; Chernoff, David; Levine, Yaakov A.
• 署名单位: Northwell Health; Northwell Health; Northwell Health; Karolinska Institutet; Karolinska University Hospital; Novartis; Novartis USA
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11144
• DOI: 10.1073/pnas.2322577121
• 发表日期: 2024-07-09
• 关键词: spinal-cord; myelin; demyelination; mechanisms; microglia; alpha-7; SYSTEM; matter; device; blood

摘要

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).