Treatment with ABR-215757 led to reduced splenic myelopoiesis, reversed neutrophilia, enhanced forelimb grip strength, and a one-third reduction in infarct size at 24 hours post-stroke.<h4>Conclusion</h4>These findings identify the spleen as a key contributor to neutrophil production following stroke and suggest that targeting S100A8/A9 may mitigate myeloid skewing and improve neurological recovery. Here, S100A8 is linked to stroke disorder.