Neutrophil extracellular traps (NETs) in cerebrovascular disease mechanisms, detection, and therapeutic targeting

Neutrophil extracellular traps (NETs) play a vital role in the pathophysiology of cerebrovascular diseases. During cerebral ischemia-reperfusion injury, NETs enhance the stability of immunothrombi by forming DNA-histone scaffolds, thereby conferring resistance to thrombolysis. They also exacerbate damage to the blood-brain barrier (BBB) by degrading tight junction proteins via activation of inflammatory cascades. Additionally, the persistent formation of NETs impedes vascular remodeling and neural repair, thereby compromising long-term functional recovery. This review comprehensively examines the complex mechanisms of NETs in stroke and related CNS disorders, focusing on key molecular pathways that regulate their formation. It summarizes current detection methodologies and targeted intervention strategies based on preclinical models, while critically evaluating the challenges associated with clinical translation. Emerging evidence indicates that targeting NETs during the acute phase may enhance reperfusion efficiency and ameliorate neural injury, whereas modulating NETs during the repair phase can promote tissue regeneration, thus offering a promising therapeutic avenue. However, clinical translation is hindered by significant obstacles, including narrow therapeutic windows, limited intervention specificity, the risk of infectious complications, and a lack of biomarkers for patient stratification. Future research should aim to elucidate NET heterogeneity, develop precise spatiotemporal modulation techniques, and advance translational applications through multidisciplinary collaboration.