Electrical stimulation of the vagus nerve ameliorates inflammation and disease activity in a rat EAE model of multiple sclerosis.
Chandramohan NatarajanLinh H D LeManojkumar GunasekaranKevin J TraceyDavid ChernoffYaakov A LevinePublished in: Proceedings of the National Academy of Sciences of the United States of America (2024)
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).
Keyphrases
- multiple sclerosis
- blood brain barrier
- white matter
- oxidative stress
- disease activity
- drug administration
- rheumatoid arthritis
- systemic lupus erythematosus
- cerebral ischemia
- end stage renal disease
- transcription factor
- spinal cord injury
- ejection fraction
- rheumatoid arthritis patients
- poor prognosis
- newly diagnosed
- ankylosing spondylitis
- genome wide
- chronic kidney disease
- mouse model
- ms ms
- inflammatory response
- prognostic factors
- big data
- long non coding rna
- spinal cord
- neuropathic pain
- patient reported outcomes
- peripheral blood
- cerebrospinal fluid
- genome wide identification
- drug induced
- atomic force microscopy
- brain injury