Myelin Damage Highly Dynamic Across Species, Study

An international collaboration led by researchers from the University of Edinburgh has revealed new information about myelin damage, which is characterized by myelin swelling. These swellings, viewed as precursors to lesions in multiple sclerosis (MS), may hold the key to understanding how early damage occurs. The findings were recently reported in Science. 

MS is known for the appearance of lesions in the brain and spinal cord. Alongside these inflamed areas, damage often occurs within myelin—the protective sheath that surrounds and insulates nerve fibers. Swellings in myelin are thought to mark the earliest stage of myelin damage. To examine how this process unfolds, researchers used advanced imaging methods and diverse biological models, ranging from zebrafish and mice to human brain tissue.

The study demonstrated that myelin swellings are far from static. They can enlarge, shrink, and even fully recover, showing a capacity for change that had not been directly observed before. The level of activity in the underlying nerve fiber appeared to play a significant role in this process. Higher activity was associated with an increase in both the number and size of swellings, while lower activity created conditions that allowed recovery to occur.

The combination of models and imaging techniques formed a central strength of the research. Conventional studies often rely on chemically fixed tissue, which halts biological motion and obscures how structures evolve. By contrast, the integration of third‑harmonic generation (THG) microscopy and two‑photon microscopy enabled the visualization of myelin changes in three dimensions over time. This unified approach allowed consistent observation across animal and human systems, capturing real‑time dynamics that static methods cannot reveal.

Following these findings, the team aims to investigate why nerve activity influences swelling behavior and what roles surrounding brain cells may play in their formation and resolution. Understanding these early changes—before actual myelin loss occurs—may inform future efforts to preserve healthy myelin and slow disease progression in MS.