stroke induced chronic neuroinflammation (PRJCA027689)

In the current study, we aimed to investigate the precise function and underlying cause of prolonged microglial activation during the chronic phase following ischemic stroke. Additionally, cholesterol metabolism in microglia in the chronic stage post-stroke remains uncertain. Herein, selective exhaustion of microglia by PLX5622 during the chronic stage ameliorated stroke-induced neurologic lesion. Stroke significantly triggered prolonged microglia activation, contributing to chronic neuroinflammation in the brain parenchyma. Simultaneously, experimental stroke evoked prominent cholesterol metabolic reprogramming in microglia and specific SAM-foamy clusters during the chronic stage. Crucially, we demonstrated that cholesterol metabolic reprogramming triggered long-lasting microglia-induced chronic neuroinflammation following stroke. Next, genetic Cyp46a1 over-expression in microglia profoundly boosted white matter repair and functional recovery after stroke. Lastly, efavirenz, an activator of CYP46A1, markedly mitigated brain lesions post-stroke.