Neuron myelination is accelerated by Bruton’s tyrosine kinase inhibition via microglial extracellular vesicles

Introduction The altered myelin repair observed in demyelinating diseases such as multiple sclerosis (MS) potentially exposes axons to various stressors, with consequent neurodegeneration. Preclinical evidence has demonstrated that Bruton’s tyrosine kinase inhibitors (BTKi), such as ibrutinib, delay MS progression by acting on myeloid cells. Methods We investigated the effects of ibrutinib on remyelination using a novel in vitro model of spinal cord neurons derived from postnatal mice. Results We demonstrated that (1) spinal cord neuron cells represent a suitable model for investigating myelination following L‑α‑lysophosphatidylcholine (LPC) treatment; (2) ibrutinib induces remyelination and reduces stathmin‑1 expression in spinal cord cultures; and (3) ibrutinib reduces the inflammatory phenotype of microglia‑like BV2 cells, thereby modulating the expression of miR‑223 in extracellular vesicles (EVs). Discussion Altogether, these data pave the way for a better understanding of the mechanisms underlying remyelination following ibrutinib treatment and support the hypothesis that EV‑derived microglial cells play a key role.