M2-associated microglial states in oligodendrocyte regulation and white matter repair in vascular dementia

Abstract

Vascular dementia (VaD), the second most common form of dementia, lacks approved disease-modifying therapies. White matter injury and demyelination are major pathological features, and oligodendrocyte-lineage damage directly limits myelin repair. M2-associated microglial responses regulate inflammation, clear cellular and myelin debris, and support oligodendrocyte differentiation and maturation. Single-cell studies, however, have exposed the limitations of the classical M1/M2 dichotomy in brain disease. In this review, M2a-, M2b-, and M2c-like states are interpreted based on experimentally specified inducing conditions and concordant molecular or functional evidence. We examine how these programs relate to oligodendrocyte injury, myelin loss, and white matter repair in VaD. with particular attention to their potentially stage-dependent contributions. Integrating these findings may inform the timing and functional focus of future interventions aimed at preserving oligodendrocyte function and promoting white matter repair in VaD.