Li Zhinuo, Wu Shao-Huang, Zhang Xinyue, Li Tianrun, Xin Mingyuan, Liu Fangxi
Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China; Key Laboratory of Neurological Disease Big Data of Liaoning Province, Shenyang, Liaoning 110001, China; Shenyang Clinical Medical Research, Shenyang, Liaoning 110001, China; Second Clinical College, Shengjing hospital of China Medical University, Shenyang 110122, China.
Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China; Key Laboratory of Neurological Disease Big Data of Liaoning Province, Shenyang, Liaoning 110001, China; Shenyang Clinical Medical Research, Shenyang, Liaoning 110001, China; Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang 110122, China.
Exp Neurol. 2026 Feb 11;400:115683. doi: 10.1016/j.expneurol.2026.115683.
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.
中性粒细胞胞外诱捕网（NETs）在脑血管疾病的病理生理学中起着至关重要的作用。在脑缺血再灌注损伤期间，NETs通过形成DNA-组蛋白支架增强免疫血栓的稳定性，从而赋予对溶栓的抗性。它们还通过激活炎症级联反应降解紧密连接蛋白，加剧血脑屏障（BBB）的损伤。此外，NETs的持续形成阻碍血管重塑和神经修复，从而损害长期功能恢复。本综述全面研究了NETs在中风及相关中枢神经系统疾病中的复杂机制，重点关注调节其形成的关键分子途径。它总结了基于临床前模型的当前检测方法和靶向干预策略，同时批判性地评估了与临床转化相关的挑战。新出现的证据表明，在急性期靶向NETs可能提高再灌注效率并改善神经损伤，而在修复期调节NETs可以促进组织再生，从而提供了一条有前景的治疗途径。然而，临床转化受到重大障碍的阻碍，包括治疗窗口狭窄、干预特异性有限、感染并发症风险以及缺乏用于患者分层的生物标志物。未来的研究应旨在阐明NET异质性，开发精确的时空调节技术，并通过多学科合作推进转化应用。
