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miRNA Expression Profiles in Cerebrospinal Fluid and Blood of Patients with Acute Ischemic Stroke

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Abstract

The aims of the study were (1) to determine whether miRNAs (microRNAs) can be detected in the cerebrospinal fluid (CSF) and blood of patients with ischemic stroke and (2) to compare these miRNA profiles with corresponding profiles from other neurological patients to address whether the miRNA profiles of CSF or blood have potential usefulness as diagnostic biomarkers of ischemic stroke. CSF from patients with acute ischemic stroke (n = 10) and patients with other neurological diseases (n = 10) was collected by lumbar puncture. Blood samples were taken immediately after. Expression profiles in the cell-free fractions of CSF and blood were analyzed by a microarray technique (miRCURY LNA™ microRNA Array, Exiqon A/S, Denmark) using a quantitative PCR (qPCR) platform containing 378 miRNA primers. In total, 183 different miRNAs were detected in the CSF, of which two miRNAs (let-7c and miR-221-3p) were found upregulated in relation to stroke. In the blood, 287 different miRNAs were detected of which two miRNAs (miR-151a-3p and miR-140-5p) were found upregulated and one miRNA (miR-18b-5p) was found downregulated in the stroke group. Some miRNAs occurred exclusively in the CSF including miR-523-3p which was detected in 50 % of the stroke patients, whereas it was completely absent in controls. Our preliminary results demonstrate that it is possible to detect and profile miRNAs in CSF and blood from patients with neurological diseases. Some miRNAs appear differentially expressed in the CSF and others in the blood of stroke patients. Currently, we are validating our results in larger groups of patients.

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Acknowledgments

This project was supported by grants from the Research Foundation of Nordsjællands Hospital, Copenhagen University; the Research Foundation for Health Research of the Capital Region of Denmark; Helen Rude’s Foundation, Dagmar Marshall’s Foundation, and the Foundation of Lily Benthine Lund.

Compliance with Ethics Requirements

ᅟ

Conflict of Interest

All the authors declare that they have no conflicts of interest.

Ethical approval

All project procedures were approved by the Danish Research Ethics Committee (project ID: H-1-2011-094) and were in accordance with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients prior to inclusion. Patients did not receive any fee for participation in the study.

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Authors and Affiliations

  1. Department of Neurology, Nordsjællands Hospital, Copenhagen University, Dyrehavevej 29, 3400, Hillerød, Denmark

    Sofie Sølvsten Sørensen, Kai Jensen & Thomas Christensen

  2. Department of Clinical Biochemistry, Nordsjællands Hospital, Copenhagen University, Hillerød, Denmark

    Ann-Britt Nygaard

  3. Department of Radiology, Nordsjællands Hospital, Copenhagen University, Hillerød, Denmark

    Ming-Yuan Nielsen

Authors
  1. Sofie Sølvsten Sørensen
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  2. Ann-Britt Nygaard
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  4. Kai Jensen
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  5. Thomas Christensen
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Corresponding author

Correspondence to Sofie Sølvsten Sørensen.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource 1

Regulation of the 144 most frequently detected miRNAs in plasma of acute ischemic stroke patients (DOC 206 kb)

Online Resource 2

Estimation of the blood brain barrier function in neurological patients based on albumin CSF/serum concentration quotients (DOC 69 kb)

Online Resource 3

Additional information on the patients included: symptoms and deficits, stroke severity, radiological findings and risk factors for ischemic stroke (DOC 58 kb)

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Sørensen, S.S., Nygaard, AB., Nielsen, MY. et al. miRNA Expression Profiles in Cerebrospinal Fluid and Blood of Patients with Acute Ischemic Stroke. Transl. Stroke Res. 5, 711–718 (2014). https://doi.org/10.1007/s12975-014-0364-8

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  • DOI: https://doi.org/10.1007/s12975-014-0364-8

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