Vagus nerve-mediated neuroimmune modulation accelerates remyelination and functional recovery in a preclinical model of multiple sclerosis

Observations of enhanced oligodendrocyte maturation signatures during vagus nerve-mediated neuroimmune modulation (VNIM) in the experimental autoimmune encephalomyelitis model of MS prompted us to test whether VNIM could promote remyelination. Here we show that VNIM, delivered as a single 1-minute treatment using clinically relevant parameters, accelerates remyelination and functional recovery in lysolecithin-induced focal demyelination.

VNIM reduced lesion volume, increased remyelinated axons with thicker myelin sheaths, enhanced debris clearance, and promoted blood-brain barrier repair. Single-cell transcriptomic analyses revealed that VNIM reshaped the lesion microenvironment by promoting microglial states associated with debris clearance and pro-repair signaling while advancing oligodendrocyte precursor maturation. Together, these findings identify VNIM as a therapeutic strategy that coordinates glial repair programs to accelerate remyelination, providing preclinical rationale for an ongoing clinical trial in relapsing-remitting MS (ClinicalTrials.gov: NCT06796504).