Correlation Analysis between NETosis Biomarkers and Peripheral Immune Cells in a Preclinical Model of Ischemic Stroke

Neutrophil extracellular traps formation (NETosis) facilitates thrombosis and contributes to reperfusion resistance - a major challenge encountered during the treatment of acute ischemic stroke. The effect of acute stroke on plasma NETosis biomarkers remains unclear. In this study, young adult C57BL/6 wildtype (WT) mice were subjected to acute brain ischemia-reperfusion (IR) injury. The IR-subjected mice exhibited a drastic increase in plasma citrullinated histone 3 (CitH3) and neutrophil elastase (NE) on day 1 (p < 0.05) while deoxyribonucleic acid (DNA) and myeloperoxidase (MPO) reached their peak levels on day 3. IR-subjected mice also showed a significant increase in peripheral neutrophils and decline in peripheral leukocytes, lymphocytes, and monocytes on day 1 and day 2 (p < 0.05). The ratios of neutrophil to lymphocyte, neutrophil to leukocyte, and lymphocyte to monocyte dramatically increased on day 1 (p < 0.05). Plasma NE, CitH3 and MPO were positively correlated with peripheral neutrophil and the ratio of neutrophil to lymphocyte, but inversely correlated with peripheral lymphocyte (p < 0.05). Our data suggest that there are time dependent changes in plasma NETosis biomarkers. Therefore, targeting these biomarkers before their peak may offer potential therapeutic options to reduce cerebral infarction and prevent functional deterioration after acute ischemic stroke.