Myelin sheaths in the central nervous system can withstand damage and dynamically remodel.

Myelin damage is a hallmark of several neurological disorders, but how it occurs remains to be fully understood. In this study, we found that early damage in zebrafish and rodent demyelination models is characterized by myelin swelling. We show, through live imaging, that myelin swelling does not always lead to myelin loss and that swellings can sometimes resolve, allowing sheaths to remodel. Increased neuronal activity during early demyelination exacerbates myelin damage, whereas reducing neuronal activity mitigates myelin swelling in both zebrafish and mice. In human multiple sclerosis tissue, myelin swelling is also dynamic and is prominent around active lesions. Our data indicate that myelin swelling is a conserved feature of demyelination and that damage to myelin sheaths can resolve, opening opportunities for targeting human disease.