Understanding How the Brain Repairs Myelin

The Plemel Lab studies how the immune system shapes injury and repair in the brain and spinal cord, with a major focus on multiple sclerosis (MS). At the centre of our research are microglia, the resident immune cells of the central nervous system. These remarkably adaptable cells can clear damaged tissue, support repair, regulate inflammation—or contribute to injury.

Our goal is to understand what determines these different responses and harness beneficial microglial functions to protect and repair the nervous system.

Microglia are diverse and dynamic

Microglia were once commonly treated as a relatively uniform population of immune cells. Our research has helped reveal a much more dynamic response. Using single-cell RNA sequencing, we showed that microglia adopt multiple distinct states following myelin injury. These populations appear and disappear at different stages of injury and repair, suggesting that microglia change their functions as the needs of the damaged tissue change. We have identified microglial populations involved in recognizing and clearing dying cells and shown that the microglial response to demyelination is substantially more diverse than previously appreciated.

This work has shifted our focus from asking simply whether microglia are “good” or “bad” to asking which microglial states perform specific functions, how microglia move between these states, and what happens when these transitions are disrupted.

Key publication: Zia et al., Molecular Neurodegeneration, 2022, Zia et al., Nature Communications, 2025

Microglia help rebuild myelin

Myelin is the fatty insulation surrounding nerve fibres that allows signals to travel rapidly through the nervous system. In MS, myelin is damaged or lost in areas called lesions. The nervous system has a remarkable capacity to replace this lost myelin through a process called remyelination, but this repair is often incomplete.

Our work has demonstrated that microglia are important participants in this regenerative process. Although microglia are well known for removing damaged myelin, we found that their contribution to repair extends beyond debris clearance. Even when the number of microglia is substantially reduced, the remaining cells can efficiently remove myelin debris, yet remyelination is still impaired. This indicates that microglia provide additional signals and functions that help create an environment in which new myelin can form.

Understanding these regenerative functions is important because promoting remyelination represents a potential strategy for protecting nerve fibres and limiting the accumulation of neurological disability in MS.

Key publication: Baaklini et al., Cell Reports, 2023–Discovery: Microglia promote remyelination through functions that extend beyond simply clearing myelin debris.

Aging changes the microglial response to repair

One of the major challenges for regeneration is aging. The ability of the central nervous system to remyelinate declines with age, at the same time that the risk of progressive neurological disability increases.

Our recent work has shown that aging does not simply make microglia less active. Instead, it disrupts the normal sequence of microglial responses during remyelination. In young animals, microglia move through a coordinated series of cellular states as damaged myelin is removed and new myelin forms. With age, these transitions become delayed and dysregulated, occurring alongside slower generation of new oligodendrocytes and impaired remyelination.

These findings suggest that successful regeneration depends not only on what microglia do, but also when they do it. Understanding why these transitions become disrupted with age may reveal new opportunities to restore a more regenerative environment in the aging nervous system.

Key Publication: Zia et al., Nature Communications, 2025–Discovery: Aging changes the microglial response to repair

From understanding microglia to promoting repair

Together, our work shows that microglia are not simply inflammatory cells. They are highly adaptable cells whose functions change across injury, inflammation, and recovery.

We combine advanced imaging, experimental models of myelin injury, molecular biology, and single-cell genomics to understand the biological rules that determine whether damaged white matter degenerates or repairs.

Our long-term goal is to translate this understanding into new ways of protecting myelin, promoting repair, and slowing neurological disability in MS and other diseases of the central nervous system.