Vagus nerve stimulation enhances remyelination and decreases innate neuroinflammation in lysolecithin-induced demyelination.

Background: Current treatments for Multiple Sclerosis (MS) poorly address chronic innate neuroinflammation nor do they offer effective remyelination. The vagus nerve has a strong regulatory role in inflammation and Vagus Nerve Stimulation (VNS) has potential to affect both neuroinflammation and remyelination in MS.
Objective: This study investigated the effects of VNS on demyelination and innate neuroinflammation in a validated MS rodent model.
Methods: Lysolecithin (LPC) was injected in the corpus callosum (CC) of 46 Lewis rats, inducing a demyelinated lesion. 33/46 rats received continuously-cycled VNS (cVNS) or one-minute per day VNS (1minVNS) or sham VNS from 2 days before LPC-injection until perfusion at 3 days post-injection (dpi) (corresponding with a demyelinated lesion with peak inflammation). 13/46 rats received cVNS or sham from 2 days before LPC-injection until perfusion at 11 dpi (corresponding with a partial remyelinated lesion). Immunohistochemistry and proteomics analyses were performed to investigate the extend of demyelination and inflammation.
Results: Immunohistochemistry showed that cVNS significantly reduced microglial and astrocytic activation in the lesion and lesion border, and significantly reduced the Olig2+ cell count at 3 dpi. Furthermore, cVNS significantly improved remyelination with 57.4 % versus sham at 11 dpi. Proteomic gene set enrichment analyses showed increased activation of (glutamatergic) synapse pathways in cVNS versus sham, most pronounced at 3 dpi.
Conclusion: cVNS improved remyelination of an LPC-induced lesion. Possible mechanisms might include modulation of microglia and astrocyte activity, increased (glutamatergic) synapses and enhanced oligodendrocyte clearance after initial injury.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Helen Bachmann, Boris Vandemoortele, Vanessa Vermeirssen, Evelien Carrette, Robrecht Raedt, Guy Laureys have nothing to disclose. Kristl Vonck received consultancy fees from LivaNova Europe and Synergia Medical. Paul Boon received consultancy fees from Livanova Europe.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)