Disturbed lipid metabolism in microglia after cerebral ischemia-reperfusion

Cerebral ischemia-reperfusion injury (CIRI) frequently compromises neurological outcomes in stroke patients despite successful recanalization therapy. While the brain's dense lipid network is integral to immune regulation and tissue repair, the spatiotemporal disruption of lipid metabolism during CIRI remains incompletely synthesized. This review critically evaluates the dynamic alterations in brain lipid profiles following ischemic injury, with a specific focus on the microglial niche. We detail how the excessive influx of extracellular lipid debris forces microglia into maladaptive, lipid-droplet-accumulating states, thereby amplifying lipotoxicity, the neuroinflammatory storm, and microglial vulnerability to ferroptosis. By integrating current evidence on lipid-driven microglial dysfunction, this review highlights the "lipid-inflammation-ferroptosis" axis as a contributing pathogenic mechanism in CIRI. Finally, we discuss the translational potential and current limitations of targeting microglial lipid metabolism, offering a balanced perspective on developing targeted metabolic interventions to enhance stroke recovery.