Neutrophil Extracellular Traps and Delayed Cerebral Ischemia in Patients With Subarachnoid Hemorrhage.

IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Journal of the American Heart Association Pub Date : 2025-10-07 Epub Date: 2025-09-19 DOI:10.1161/JAHA.124.041325
Hauke Schneider, Diana Münch, Valérie Spalart, Mathias Stroobants, Ansgar Berlis, Christoph J Maurer, Ulrich Jaschinski, Scott E Kasner, Quy Cao, Kimberly Martinod, Jens Witsch
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引用次数: 0

Abstract

Background: Delayed cerebral ischemia (DCI) after spontaneous subarachnoid hemorrhage (SAH) is not well understood. Recent studies suggest the involvement of neutrophil-mediated immunothrombosis via neutrophil extracellular traps (NETs). We aimed to assess whether trajectories of NET biomarkers in patients with acute SAH are associated with DCI.

Methods: This was a prospective single-center study of patients within 48 hours of SAH onset. We collected clinical, laboratory, imaging, and 3-month outcome data. NET markers (H3Cit [citrullinated histone H3]-DNA complexes, myeloperoxidase-DNA complexes, cell-free DNA), along with peptidylarginine deiminase 4, and deoxyribonuclease activity were measured in plasma collected on admission (baseline), and post-SAH days 5 and 10. DCI was defined by clinical and imaging criteria. Generalized estimating equations examined differences in NET trajectories comparing patients with and without DCI.

Results: We enrolled 40 patients with SAH (mean age, 57 years; n=21 [53%] women; 32 [80%] aneurysmal). DCI occurred in 12 (30%) patients. All NET levels were similar between groups at baseline. On day 5, those with DCI compared with those without DCI had elevated median H3Cit-DNA complex (63 ng/mL versus 31 ng/mL, P=0.049), myeloperoxidase-DNA complex (5.9 ng/mL versus 0.4 ng/mL, P=0.029), and cell-free DNA (651 ng/mL versus 515 ng/mL, P=0.04) levels, which trended back down on day 10. In the DCI group, generalized estimating equations indicated heightened trajectories of H3Cit-DNA complex (day 5 [compared with baseline]: β=0.7; SE, 0.3; P=0.01; day 10: β=0.5; SE, 0.3; P=0.09), and myeloperoxidase-DNA complex levels (day 5: β=3.1; SE, 0.4; P<0.001; day 10: β=1.6; SE, 1.0; P=0.10).

Conclusions: In patients with acute SAH, elevated plasma trajectories of NETs are associated with DCI.

中性粒细胞胞外陷阱与蛛网膜下腔出血患者迟发性脑缺血。
背景:自发性蛛网膜下腔出血(SAH)后迟发性脑缺血(DCI)尚不清楚。最近的研究表明,中性粒细胞介导的免疫血栓形成通过中性粒细胞胞外陷阱(NETs)参与。我们的目的是评估急性SAH患者的NET生物标志物轨迹是否与DCI相关。方法:这是一项前瞻性单中心研究,研究对象是SAH发病48小时内的患者。我们收集了临床、实验室、影像学和3个月的结果数据。入院时(基线)和sah后第5天和第10天收集血浆,测量NET标记物(H3Cit[瓜氨酸组蛋白H3]-DNA复合物,髓过氧化物酶-DNA复合物,细胞游离DNA),以及肽精氨酸脱亚胺酶4和脱氧核糖核酸酶活性。DCI由临床和影像学标准定义。广义估计方程检验了有DCI和没有DCI的患者在NET轨迹上的差异。结果:我们招募了40例SAH患者(平均年龄57岁,女性21例(53%),动脉瘤32例(80%))。12例(30%)患者发生DCI。所有NET水平在基线时各组之间相似。在第5天,与没有DCI的患者相比,DCI患者的h3cto -DNA复合物(63 ng/mL比31 ng/mL, P=0.049)、髓过氧化物酶-DNA复合物(5.9 ng/mL比0.4 ng/mL, P=0.029)和无细胞DNA (651 ng/mL比515 ng/mL, P=0.04)水平中位数升高,在第10天呈下降趋势。在DCI组中,广义估计方程表明h3cto - dna复合物(第5天[与基线相比]:β=0.7; SE, 0.3; P=0.01;第10天:β=0.5; SE, 0.3; P=0.09)和髓过氧化物酶- dna复合物水平(第5天:β=3.1; SE, 0.4; PP=0.10)的轨迹升高。结论:在急性SAH患者中,NETs血浆轨迹升高与DCI相关。
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来源期刊
Journal of the American Heart Association
Journal of the American Heart Association CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
9.40
自引率
1.90%
发文量
1749
审稿时长
12 weeks
期刊介绍: As an Open Access journal, JAHA - Journal of the American Heart Association is rapidly and freely available, accelerating the translation of strong science into effective practice. JAHA is an authoritative, peer-reviewed Open Access journal focusing on cardiovascular and cerebrovascular disease. JAHA provides a global forum for basic and clinical research and timely reviews on cardiovascular disease and stroke. As an Open Access journal, its content is free on publication to read, download, and share, accelerating the translation of strong science into effective practice.
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