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 neuro-immune-metabolic network system disease 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 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 current promising treatment strategies and the clinical transformation of emerging technologies. In summary, an integrated neuro-immune-metabolic framework is proposed to understand stroke as a systemic disease, and to guide the combined therapies that target the center nervous system and the periphery organs to realize the transformation from local intervention to systemic treatment.