Cholesterol metabolic reprogramming mediates microglia-induced chronic neuroinflammation and hinders neurorestoration following stroke.

ABSTRACT: Chronic neuroinflammation is a major obstacle to post-stroke recovery, yet the underlying mechanisms, particularly the link between prolonged microglial activation and cholesterol metabolism, are not fully known. Here we show that ischaemic injury induces persistent microglial activation that perpetuates chronic inflammation, leading to microglial cholesterol accumulation and metabolic reprogramming. Using single-cell RNA sequencing, we identified distinct stroke-associated foamy microglia clusters characterized by extensive reprogramming of cholesterol metabolism. Furthermore, direct intracerebral free cholesterol or cholesterol crystal infusion recapitulated sustained microglial activation, directly linking aberrant cholesterol metabolism to prolonged neuroinflammatory responses. Therape

SUBMITTER: Zhao Q 

PROVIDER: S-EPMC12552130 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature