Microglial intervention in ischemic stroke: roles and intervention strategies

Abstract Ischemic stroke is a major cause of neurological deficits and high disability rate. As the primary immune cells of the central nervous system, microglia play dual roles in neuroinflammation and tissue repair following a stroke. Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes. This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies. Microglia exhibit a dynamic functional state, transitioning between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. This duality is crucial in ischemic stroke, as it maintains a balance between neuroinflammation and tissue repair. Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood–brain barrier, while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration. Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B, mitogen-activated protein kinases, Janus kinase/signal transducer and activator of transcription, and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways. These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage. Potential therapeutic agents include natural compounds found in drugs such as minocycline, as well as traditional Chinese medicines. Drugs that target these regulatory mechanisms, such as small molecule inhibitors and components of traditional Chinese medicines, along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics, offer new therapeutic strategies and clinical translational potential for ischemic stroke.