The neuro-immune-metabolic network in ischemic stroke: mechanisms and therapeutic targeting of brain-peripheral organ crosstalk

Ischemic stroke is traditionally regarded as a focal brain injury, but recent studies have shown that it is essentially a disease of the neuro-immune-metabolic network involving multiple organs. This article reviews the two-way dialogue between the brain and the gut, heart, liver, spleen, lung, and kidney through autonomic nerves, immune-mediated inflammation, and metabolic pathways. Building on this framework, we delve into the dysregulation of brain-peripheral organ axes following ischemic stroke, focusing on key molecular hubs that drive the systemic pathological process. We then discuss the promising current treatment strategies and the clinical translation of emerging technologies. In summary, an integrated neuro-immune-metabolic framework is proposed to understand ischemic stroke as a systemic disease and to guide combined therapies that target the central nervous system and the peripheral organs to realize the transformation from local intervention to systemic treatment.