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蛛网膜下腔出血患者早期脑损伤期间脑脊液微小RNA谱作为生物标志物的研究

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

作者信息

Pedrosa Leire, Hoyos Jhon, Reyes Luis, Llull Laura, Santana Daniel, de Riva Nicolás, Mellado Ricard, Sala Xavier, Rodríguez-Hernández Ana, Enseñat Joaquim, Amaro Sergio, Torné Ramon

机构信息

August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.

Department of Neurosurgery, Institute of Neuroscience, Hospital Clinic of Barcelona, Barcelona, Spain.

出版信息

Front Cell Neurosci. 2022 Nov 25;16:1016814. doi: 10.3389/fncel.2022.1016814. eCollection 2022.

Abstract

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

引言

迟发性脑缺血(DCI)是自发性蛛网膜下腔出血(SAH)患者中高达30%会出现的一种可怕并发症。事实上,DCI是SAH患者长期残疾的主要原因之一,然而在病情较差的SAH病例中,其预测和预防都很棘手。在这项前瞻性研究中,我们探讨了微小核糖核酸(microRNA,缩写为miRNAs)——参与转录后水平线索基因调控的小非编码RNA——作为SAH患者神经学预后生物标志物的潜在作用。

方法

我们分析了SAH患者在疾病早期(出血后第三天)脑脊液(CSF)中几种miRNAs的表达情况。使用纳米串技术对CSF样本进行表征。

结果

我们发现与10名非SAH对照相比,57例SAH急性期的miRNAs表达上调。此外,根据临床发病的严重程度,以及DCI的发生和中期功能预后,检测到特定miRNAs存在差异表达。

结论

这些观察结果强化了miRNAs作为SAH患者预后和诊断生物标志物的潜在效用。此外,鉴定与SAH演变相关的特定miRNAs可能有助于深入了解其对病理生理途径的调控功能,如转化生长因子-β炎症途径和血脑屏障破坏。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0636/9732100/c2b5a3a8a87b/fncel-16-1016814-g001.jpg

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