microRNA cerebrospinal fluid profile during the early brain injury period as a biomarker in subarachnoid hemorrhage patients

Delayed cerebral ischemia (DCI) is a dreadful complication present in up to 30% of patients with spontaneous subarachnoid hemorrhage (SAH). Indeed, DCI is one of the main causes of long-term disability in SAH, yet its prediction and prevention are troublesome in poor-grade SAH cases. In this prospective study, we explored the potential role of micro ribonucleic acid (microRNA, abbreviated miRNAs), – small non-coding RNAs involved in clue gene regulation at the post-transcriptional level – as biomarkers of neurological outcomes in SAH patients. We analyzed the expression of several miRNAs present in the cerebrospinal fluid (CSF) of SAH patients during the early stage of the disease (third-day post-hemorrhage). NanoString Technologies were used for the characterization of the CSF samples. We found an overexpression of miRNAs in the acute stage of 57 SAH in comparison with 10 non-SAH controls. Moreover, a differential expression of specific miRNAs was detected according to the severity of clinical onset, but also regarding the development of DCI and the midterm functional outcomes. These observations reinforce the potential utility of miRNAs as prognostic and diagnostic biomarkers in SAH patients. In addition, the identification of specific miRNAs related to SAH evolution might provide insights into their regulatory functions of pathophysiological pathways, such as the TGF-β inflammatory pathway and blood-brain barrier disruption We have studied the miRNA expression of CSF samples from the third day of hemorraghe onset of SAH patients and CSF samples from healthy patients.

迟发性脑缺血（Delayed cerebral ischemia, DCI）是自发性蛛网膜下腔出血（spontaneous subarachnoid hemorrhage, SAH）患者中发生率高达30%的严重并发症。事实上，迟发性脑缺血是自发性蛛网膜下腔出血患者长期残疾的主要诱因之一，但在病情危重的自发性蛛网膜下腔出血病例中，其预测与预防仍颇具挑战。本前瞻性研究探讨了微核糖核酸（microRNA，缩写为miRNAs）——一类参与转录后水平关键基因调控的小型非编码核糖核酸——作为自发性蛛网膜下腔出血患者神经功能转归生物标志物的潜在价值。我们分析了发病早期（出血后第3天）的自发性蛛网膜下腔出血患者脑脊液（cerebrospinal fluid, CSF）中多种微核糖核酸的表达水平。本研究采用奈斯特技术（NanoString Technologies）对脑脊液样本进行表征分析。相较于10例非自发性蛛网膜下腔出血对照者，我们在57例急性期自发性蛛网膜下腔出血患者的样本中发现了微核糖核酸的过表达现象。此外，根据临床起病严重程度、迟发性脑缺血的发生情况以及中期功能转归，可检测到特定微核糖核酸的差异表达。上述研究结果进一步证实了微核糖核酸作为自发性蛛网膜下腔出血患者预后与诊断生物标志物的潜在应用价值。此外，鉴定与自发性蛛网膜下腔出血病程相关的特定微核糖核酸，或可揭示其在病理生理通路中的调控功能，例如转化生长因子-β（TGF-β）炎症通路以及血脑屏障破坏过程。本研究对自发性蛛网膜下腔出血患者出血后第3天的脑脊液样本，以及健康受试者的脑脊液样本中的微核糖核酸表达水平进行了分析。