Genchi Angela, Semerano Aurora, Gullotta Giorgia Serena, Strambo Davide, Schwarz Ghil, Bergamaschi Andrea, Panni Pietro, Simionato Franco, Scomazzoni Francesco, Michelozzi Caterina, Pozzato Mattia, Maugeri Norma, Comi Giancarlo, Falini Andrea, Roveri Luisa, Filippi Massimo, Martino Gianvito, Bacigaluppi Marco
Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy; Neurology Department, IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
J Neurol Sci. 2021 Apr 15;423:117355. doi: 10.1016/j.jns.2021.117355. Epub 2021 Feb 21.
Inflammation is emerging as an essential trigger for thrombosis. In the interplay between innate immunity and coagulation cascade, neutrophils and neutrophil extracellular traps (NETs) can promote thrombus formation and stabilization. In ischemic stroke, it is uncertain whether the involvement of the inflammatory component may differ in thrombi of diverse etiology. We here aimed to evaluate the presence of neutrophils and NETs in cerebral thrombi of diverse etiology retrieved by endovascular thrombectomy (EVT).
We performed a systematic histological analysis on 80 human cerebral thrombi retrieved through EVT in acute ischemic stroke patients. Thrombus composition was investigated in terms of neutrophils (MPO cells) and NET content (citH3 area), employing specific immunostainings. NET plasma content was determined and compared to NET density in the thrombus.
Neutrophils and NETs were heterogeneously represented within all cerebral thrombi. Thrombi of diverse etiology did not display a statistically significant difference in the number of neutrophils (p = 0.51). However, NET content was significantly increased in cardioembolic compared to large artery atherosclerosis thrombi (p = 0.04), and the association between NET content and stroke etiology remained significant after adjusted analysis (beta coefficient = -6.19, 95%CI = -11.69 to -1.34, p = 0.01). Moreover, NET content in the thrombus was found to correlate with NET content in the plasma (p ≤ 0.001, r = 0.62).
Our study highlights how the analysis of the immune component within the cerebral thrombus, and specifically the NET burden, might provide additional insight for differentiating stroke from diverse etiologies.
炎症正逐渐成为血栓形成的重要触发因素。在固有免疫与凝血级联反应的相互作用中，中性粒细胞和中性粒细胞胞外诱捕网（NETs）可促进血栓形成和稳定。在缺血性卒中中，炎症成分在不同病因血栓中的参与情况是否存在差异尚不确定。我们旨在评估通过血管内血栓切除术（EVT）获取的不同病因脑内血栓中中性粒细胞和NETs的存在情况。
我们对80例急性缺血性卒中患者通过EVT获取的人脑血栓进行了系统的组织学分析。采用特异性免疫染色，从嗜中性粒细胞（MPO细胞）和NET含量（citH3面积）方面研究血栓成分。测定NET血浆含量并与血栓中的NET密度进行比较。
所有脑内血栓中中性粒细胞和NETs的表现存在异质性。不同病因的血栓在中性粒细胞数量上无统计学显著差异（p = 0.51）。然而，与大动脉粥样硬化血栓相比，心源性栓塞血栓中的NET含量显著增加（p = 0.04），调整分析后NET含量与卒中病因之间的关联仍然显著（β系数 = -6.19，95%CI = -11.69至 -1.34，p = 0.01）。此外，发现血栓中的NET含量与血浆中的NET含量相关（p≤0.001，r = 0.62）。
我们的研究强调了对脑内血栓免疫成分的分析，特别是NET负荷，可能为区分不同病因的卒中提供额外的见解。
