Yang Bosco Seong Kyu, Tabassum Sidra, Hinds Sarah, O'Keefe Lena M, Wu Silin, Paz Atzhiry S, Chen Hua, Gusdon Aaron M, Ren Xuefang, Choi Huimahn A
Res Sq. 2025 Apr 1:rs.3.rs-6198784. doi: 10.21203/rs.3.rs-6198784/v1.
Delayed cerebral ischemia (DCI) is a potentially preventable complication from an aneurysmal subarachnoid hemorrhage (SAH). The micro-RNAs (miR) 34 family has shown its ability to disrupt the blood-brain barrier and redox metabolism and might contribute to the complex pathophysiology of DCI. This study aimsto evaluate the association between the serum levels of miR-34c and the occurrence of DCI. This retrospective observational study is based on 72 subjects with acute aneurysmal SAH who were admitted to a single tertiary center between December 2017 and July 2021. Subjects were prospectively adjudicated for clinical outcomes, including delayed cerebral ischemia.Levels of miR-34c were measured in plasma collected within 48 hours of ictus. Patients were median-dichotomized into having a higher or lower plasma level of miR-34c. miR34c levels were compared between DCI and no DCI groups using the Wilcoxon rank sum tests. A multivariable logistic regression model and the Cox proportional hazard model were used to evaluate the effect of higher miR-34c levels. The median age was 54 years, 76% were females, and 21% developed DCI. Early miR-34c levels were significantly higher in SAH subjects who progressed to have DCI with Cohen's of 0.75 (p<0.05). Even after adjusting for age, sex, histories of diabetes, hypertension, Hunt-Hess grade, and modified Graeb scores, a higher miR-34c level was associated with 5.7-fold increased odds of DCI (p<0.05; 95% CI: 1.35-32.22). Survival analysis adjusting for the known predictors also revealeda 5.4-fold higher hazard of DCI for the patients with a higher miR-34c level (p < 0.05; 95% CI 1.22-25.43). The present study demonstrates the potential importance of circulating miR-34c in predicting DCI in SAH patients. Given the known importance of the miR-34 family in vascular physiology, it may be an important target for future studies.
迟发性脑缺血(DCI)是动脉瘤性蛛网膜下腔出血(SAH)一种潜在可预防的并发症。微小RNA(miR)34家族已显示出破坏血脑屏障和氧化还原代谢的能力,可能在DCI复杂的病理生理学中起作用。本研究旨在评估血清miR - 34c水平与DCI发生之间的关联。这项回顾性观察性研究基于2017年12月至2021年7月期间入住一家三级中心的72例急性动脉瘤性SAH患者。前瞻性判定患者的临床结局,包括迟发性脑缺血。在发病后48小时内采集的血浆中测量miR - 34c水平。将患者按血浆miR - 34c水平高低进行中位数二分法分组。使用Wilcoxon秩和检验比较DCI组和无DCI组的miR34c水平。采用多变量逻辑回归模型和Cox比例风险模型评估较高miR - 34c水平的影响。中位年龄为54岁,76%为女性,21%发生了DCI。进展为DCI的SAH患者早期miR - 34c水平显著更高,科恩效应量为0.75(p<0.05)。即使在调整年龄、性别、糖尿病史、高血压史、Hunt - Hess分级和改良Graeb评分后,较高的miR - 34c水平与DCI发生几率增加5.7倍相关(p<0.05;95%CI:1.35 - 32.22)。对已知预测因素进行调整的生存分析还显示,miR - 34c水平较高的患者发生DCI的风险高5.4倍(p < 0.05;95%CI 1.22 - 25.43)。本研究证明了循环miR - 34c在预测SAH患者发生DCI方面的潜在重要性。鉴于miR - 34家族在血管生理学中的已知重要性,它可能是未来研究的一个重要靶点。