Abstract TP218: Functional Dynamics of Neutrophil After Ischemic Stroke

Abstract

Background and purpose: Neutrophil is forerunner to the brain lesion after ischemic stroke and exerts elaborate functions. However, temporal alterations of cell count, polarity, extra cellular trap formation and clearance of neutrophil remain poorly understood. The current study aimed at providing basic information of neutrophil functional time course. Methods: A total of 225 patients were included in the study. Correlation of neutrophil in peripheral blood and stroke outcomes were analyzed. Dynamics of neutrophil cell count and immune-modulatory functions were assessed with flow cytometry, immune-staining, quantitative PCR. In vitro study was conducted to describe the impact of neutrophil phenotype to macrophage and neuronal death after ischemic injury. Results: Higher neutrophil count in patient blood within 24 hours after symptom onset indicated detrimental stroke outcomes. The peak of neutrophil in ischemic brain lesion (1-2d) was right after that of peripheral blood (12h) in mice. Expression of CD206, a N2 marker, was relatively stable in infiltrated neutrophil within stroke lesion. Clearance of neutrophil peaked at 2d after stroke and extra cellular traps were most detected at 2-3d after stroke. N2 phenotype facilitated neutrophil clearance by macrophage and did not further induced neuronal death after ischemic injury. Conditioned medium of ischemic neurons drove neutrophil away from the protective N2 phenotype and increased formation of extracellular traps. Conclusions: Neutrophil functions had important impact on stroke outcomes. Neutrophil in patient blood could be an early indicators of stroke outcomes. N2 neutrophil facilitated macrophage phagocytosis and was less harmful to ischemic neurons. Directing neutrophil towards N2 phenotype could be a promising therapeutic scheme for ischemic stroke.