Block of a subset of sodium channels exacerbates experimental autoimmune encephalomyelitis

Abstract

Voltage-gated sodium channels (Na(v)s) are involved in several aspects of the pathogenesis of multiple sclerosis (MS). Within acute MS plaques, they are expressed along demyelinated axons. Studies in experimental autoimmune encephalomyelitis (EAE) demonstrated a neuroprotective effect of non-specific Na-v blockers. Further, block of specific Na(v)s involved in MS is suggested to have an advantage over non-specific blockers. We investigated the effects of the synthetic Midi peptide in EAE, as it potently and specifically blocks Na(v)1.2, Na(v)1.4 and Na(v)1.6. Administration of this Midi peptide worsens the clinical disease pattern and Na(v)1.2 and Na(v)1.6 expression levels were elevated in brain but not in spinal cord of Midi-treated mice, implicating that Nays play a complex role in the pathogenesis of EAE. (C) 2013 Elsevier B.V. All rights reserved.