Interplay between lipid metabolism and macrophage dynamics in ischemic stroke: From mechanistic insights to therapeutic strategies

Ischemic stroke (IS), a leading global cause of long-term disability, is treated with therapies (e.g., thrombolysis, mechanical thrombectomy) constrained by a narrow therapeutic window and ischemia-reperfusion injury risks. Neuroinflammation-exhibiting dual, time-dependent (protective vs. harmful) effects-complicates static targeting. Macrophages, encompassing resident microglia and infiltrating blood-derived macrophages, regulate neuroinflammation via marked heterogeneity and metabolic reprogramming in the dynamic IS microenvironment. Herein, we review metabolic reprogramming in the IS milieu, lipid metabolism in IS-associated macrophages, its functional consequences, therapeutic targets, and emerging approaches. Additionally, we address current challenges and future directions, and highlight translational perspectives in IS. In summary, macrophages emerge as metabolic hubs in IS, with lipid metabolism as a critical targetable axis for improving stroke therapy.