Acute ischemic stroke is often complicated by infections and extracerebral organ dysfunction, which compromise the benefits of reperfusion therapy and independently predict poor outcomes including disability and death. Accumulating evidence indicates that these complications arise from the disruption of the bidirectional central-peripheral immune communication network, rather than being isolated organ-specific events. As the earliest and most abundant innate responders to acute ischemic stroke, neutrophils act as pivotal integrators in this intersystem crosstalk, orchestrating cellular, molecular, and organ-level interactions. Post-stroke, danger signals derived from the central nervous system rapidly trigger emergency granulopoiesis, mobilizing neutrophils from bone marrow and splenic reservoirs into the circulation. Within the brain, recruited neutrophils exacerbate secondary injury through degranulation, reactive oxygen species production, and neutrophil extracellular trap formation, thereby promoting blood-brain barrier breakdown, edema, and hemorrhagic transformation. Concurrently, neutrophils serve as messengers to transmit brain injury signals to peripheral immune compartments and organs, reshaping systemic immunity and driving organ-specific pathology. Importantly, peripheral infections and organ dysfunction reciprocally amplify neuroinflammation via neutrophil reprogramming and inflammatory mediator release, forming a self-reinforcing pathological loop. This review synthesizes current mechanistic and translational evidence to systematically elaborate on neutrophils' triple roles as "cell communication bridges, signal transduction carriers, and organ axis mediators" in post-stroke pathophysiology. Additionally, we discuss key role of the sympathetic nervous system in this pathological process, and summarize emerging targeted immune therapeutic strategies, supporting that targeting neutrophil-mediated central-periphery communication and sympathetic nervous system modulation represent a promising therapeutic approach to improve neurological recovery while mitigating systemic morbidity after stroke.
Ye et al. (Sat,) studied this question.