Metabolic reprogramming of oligodendrocyte lineage cells in ischemic stroke: Insights from literature review and a...

Ischemic stroke (IS) causes white matter (WM) injury and disrupts myelin integrity, contributing to long-term cognitive dysfunction. Oligodendrocyte lineage cells, particularly oligodendrocyte precursor cells (OPCs), are essential for post-stroke remyelination, yet their survival, differentiation, and myelin-forming capacity are highly dependent on metabolic state. However, a systematic overview of these metabolic changes post-stroke is still lacking. Here, we review current knowledge on the crosstalk between classical pathways and oligodendrocyte lineage metabolism in IS, integrating evidence from recent studies and complementing them with a re-analysis of three independent single-cell RNA sequencing (scRNA-seq) datasets from mouse stroke models covering hyperacute, acute, and chronic recovery phases. This re-analysis highlighted stage-specific alterations in oxidative phosphorylation, inositol phosphate metabolism, and sphingolipid metabolism within OPCs, alongside activation of cholesterol biosynthesis in mature oligodendrocytes (OLs). These findings are consistent with evidence linking these pathways to oligodendrocyte lineage progression and WM repair. Together, the literature and re-analysis support the notion that oligodendrocyte lineage metabolism is an important regulator of post-stroke remyelination and may provide potential therapeutic targets for promoting cognitive function.