Iacobucci Marta, Risitano Angela, Amisano Paolo, Berto Irene, Carnevale Roberto, Cammisotto Vittoria, Biraschi Francesco, Cirelli Carlo, Di Mascio Maria Teresa, Toni Danilo, Lorenzano Svetlana, De Michele Manuela
Neuroradiology Unit, Umberto I Hospital, Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy.
Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy.
Int J Mol Sci. 2025 Mar 30;26(7):3205. doi: 10.3390/ijms26073205.
Good leptomeningeal collaterals (LMCs) after large vessel occlusion (LVO) extend the time window for endovascular therapy. The mechanisms regulating LMC activation are not fully understood. The aim of this study was to investigate the potential role of two vasoactive molecules endothelin-1 (ET-1)-a vasoconstrictor agent-and nitric oxide (NO)-a vasodilator agent-in the regulation of post-stroke LMCs. Ischemic stroke patients within 6 h of LVO were included. Collateral status was assessed using the Menon scoring system based on computed tomography angiography scans. Patients were accordingly divided into three groups: poor, intermediate, and good LMCs. Recanalization was evaluated using the modified thrombolysis in cerebral infarction (mTICI) score. Serum levels of ET-1 and NO were measured at three time points: T0 (<6 h), T1 (24 h), and T2 (48 h). A total of 105 patients were enrolled (mean age 76 ± 12.8 years): 44 with good (46.2%), 36 with intermediate (37.8%), and 22 with poor LMCs (23.1%). NO values decreased, whereas ET-1 values increased from T0 to T1 in all groups of patients. No significant association was found between serum ET-1 levels and collateral status. Higher ET-1 levels at T1 correlated with poor outcome regardless of the LMC status or the degree of recanalization ( = 0.030). A significant linear positive correlation was revealed at T0 between high levels of ET-1 and the neutrophil count (Spearman's rho = 0.236, = 0.035). Subgroup analysis showed a significant inverse correlation at T1 between NO and the collateral score (Spearman's rho = -0.251, = 0.021). Although we observed no significant association between LMC score and serum ET-1 concentrations, at 24 h higher ET-1 serum levels were predictive of poor outcome and higher NO levels were correlated with poor collateral status. These findings may indicate an inadequate microvascular reperfusion, possibly due to ET-1-mediated vasoconstriction, neutrophil activation, and NO-mediated oxidative stress, suggesting their potential role in the no-reflow phenomenon.
大血管闭塞（LVO）后良好的软脑膜侧支循环（LMCs）可延长血管内治疗的时间窗。调节LMC激活的机制尚未完全明确。本研究旨在探讨两种血管活性分子——血管收缩剂内皮素-1（ET-1）和血管扩张剂一氧化氮（NO）——在中风后LMC调节中的潜在作用。纳入LVO后6小时内的缺血性中风患者。基于计算机断层血管造影扫描，使用梅农评分系统评估侧支循环状态。患者据此分为三组：LMCs差、中等和良好。使用改良的脑梗死溶栓（mTICI）评分评估再通情况。在三个时间点测量血清ET-1和NO水平：T0（<6小时）、T1（24小时）和T2（48小时）。共纳入105例患者（平均年龄76±12.8岁）：44例LMCs良好（46.2%），36例中等（37.8%），22例差（23.1%）。所有患者组中，从T0到T1，NO值降低，而ET-1值升高。血清ET-1水平与侧支循环状态之间未发现显著关联。无论LMC状态或再通程度如何，T1时较高的ET-1水平与不良预后相关（P = 0.030）。T0时，高水平的ET-1与中性粒细胞计数之间存在显著的线性正相关（Spearman秩相关系数=0.236，P = 0.035）。亚组分析显示，T1时NO与侧支循环评分之间存在显著的负相关（Spearman秩相关系数=-0.251，P = 0.021）。尽管我们未观察到LMC评分与血清ET-1浓度之间存在显著关联，但在24小时时，较高的ET-1血清水平预示着不良预后，而较高的NO水平与不良侧支循环状态相关。这些发现可能表明微血管再灌注不足，可能是由于ET-1介导的血管收缩、中性粒细胞激活以及NO介导的氧化应激，提示它们在无复流现象中的潜在作用。
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