Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2024 Nov 13;15:1477669. doi: 10.3389/fimmu.2024.1477669. eCollection 2024.
Acute ischemic stroke represents a critical, life-threatening condition affecting the central nervous system. Intravenous thrombolysis with tissue plasminogen activator (tPA) remains a cornerstone for achieving vascular recanalization in such patients; however, its therapeutic utility is limited, with only approximately 10% of patients benefiting due to the narrow therapeutic window and significant risk of hemorrhagic transformation. Enhancing the efficacy of tPA thrombolysis is therefore imperative. Neutrophils have been identified as key modulators of thrombolytic outcomes, interacting with tPA post-stroke to influence treatment effectiveness. The binding of tPA to low-density lipoprotein receptor-related protein 1 (LRP-1) on neutrophil surfaces induces degranulation and formation of neutrophil extracellular traps (NETs). Conversely, neutrophils impede the thrombolytic action of tPA by obstructing its interaction with fibrin and activating platelets. These findings suggest that targeting neutrophils may hold promise for improving thrombolysis outcomes. This review explores the role of neutrophils in tPA-mediated thrombolysis following acute ischemic stroke, examines neutrophil-associated biomarkers, and outlines potential strategies for enhancing tPA efficacy.
急性缺血性脑卒中是一种影响中枢神经系统的危急生命的病症。在这类患者中，静脉注射组织型纤溶酶原激活剂（tPA）仍然是实现血管再通的基石；然而，其治疗效果有限，由于治疗窗狭窄和出血转化的风险较大，仅有约 10%的患者从中受益。因此，提高 tPA 溶栓的疗效势在必行。中性粒细胞已被确定为影响溶栓效果的关键调节剂，其在中风后与 tPA 相互作用，影响治疗效果。tPA 与中性粒细胞表面的低密度脂蛋白受体相关蛋白 1（LRP-1）结合，诱导脱颗粒和形成中性粒细胞胞外诱捕网（NETs）。相反，中性粒细胞通过阻碍其与纤维蛋白的相互作用和激活血小板来阻碍 tPA 的溶栓作用。这些发现表明，靶向中性粒细胞可能有希望改善溶栓效果。本综述探讨了中性粒细胞在急性缺血性脑卒中后 tPA 介导的溶栓中的作用，研究了中性粒细胞相关的生物标志物，并概述了增强 tPA 疗效的潜在策略。
