Neutrophil Extracellular Traps in Ischemic Stroke Thrombi Are Associated Wth Poor Clinical Outcome

BACKGROUND: Acute ischemic stroke is a neurologic emergency associated with severe disability and death. There is growing evidence that neutrophil extracellular traps (NETs) contribute to the pathogenesis of acute stroke. By mechanical removal of the occluding thrombus from the patient's vasculature, endovascular thrombectomy enables the collection of thrombus material for immunohistologic analysis. The aim of our study was to strengthen the association of NET content in ischemic thrombi with clinical outcome and guide future therapeutics. METHODS: We performed an immunohistologic analysis of thrombi from 101 patients with acute ischemic stroke, focusing on the association between NET content and clinical and interventional indicators. RESULTS: NETs were present in every patient with acute ischemic stroke. Their abundance in thrombi was associated with interventional markers of thrombus stability. NET-rich thrombi were associated with unsuccessful recanalization (modified Thrombolysis in Cerebral Infarction <2B) and longer procedure time, and NET abundance in acute ischemic stroke thrombi was associated with outcomes evaluated by patients' postassessment National Institutes of Health Stroke Scale and modified Rankin Scale scores. CONCLUSION: These findings suggest that NET content is critically important to thrombus stability and clinical outcome in acute stroke. They should open new perspectives for innovative immunotherapy strategies based on neutrophil modulation.