Elevation of brain-enriched miRNAs in cerebrospinal fluid of patients with acute ischemic stroke

Biomarker Research

Niels H. H. Heegaard¹  Anting Liu Carlsen¹  Mads Bak²  Ann-Britt Nygaard³  Thomas Christensen⁴  Sofie Sølvsten Sørensen⁴ 

[1] Department of Autoimmunology and Biomarkers, Statens Serum Institut;Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen;Department of Clinical Biochemistry, Nordsjællands Hospital;Department of Neurology, Nordsjællands Hospital, University of Copenhagen;

关键词: Stroke;    MicroRNA;    Biomarkers;    Brain ischemia;    Cerebrospinal fluid;   

DOI  :  10.1186/s40364-017-0104-9

来源: DOAJ

【 摘 要 】

Abstract Background The purpose of this study was to investigate the potential of cerebrospinal fluid miRNAs as diagnostic biomarkers of acute ischemic stroke using three different profiling techniques in order to identify and bypass any influence from technical variation. Methods Cerebrospinal fluid (CSF) from patients with acute ischemic stroke (n = 21) and controls (n = 21) was collected by lumbar puncture. miRNA analysis was performed with three different methods: 1) Trizol RNA extraction followed by Illumina Next Generation Sequencing (NGS) on all small RNAs, 2) Exiqon RNA extraction protocol and miRNA qPCR assays, and 3) validation of 24 selected miRNAs with Norgen Biotek RNA extraction protocol and Applied Biosystems qPCR assays. Results NGS detected 71 frequently expressed miRNAs in CSF of which brain-enriched miR-9-5p and miR-128-3p were significantly higher in CSF of stroke patients compared to controls. When dividing stroke patients into groups according to infarct size several brain-enriched miRNAs (miR-9-5p, miR-9-3p, miR-124-3p, and miR-128-3p) were elevated in patients with infarcts >2 cm3. This trend appeared in data from both NGS, qPCR (Exiqon), and qPCR (Applied Biosystems) but was only statistically significant in some of the measurement platforms. Conclusions Several brain-enriched miRNAs are elevated in the CSF three days after stroke onset, suggesting that these miRNAs reflect the brain damage caused by ischemia. The expression differences seem, however, limited to patients with larger ischemic brain injury, which argues against the use of CSF miRNAs as diagnostic biomarkers of stroke based on current methods.

【 授权许可】

Unknown