Cargando…

Hemorrhagic Stroke Induces a Time-Dependent Upregulation of miR-150-5p and miR-181b-5p in the Bloodstream

To date, the only effective pharmacological treatment for ischemic stroke is limited to the clinical use of recombinant tissue plasminogen activator (rtPA), although endovascular therapy has also emerged as an effective treatment for acute ischemic stroke. Unfortunately, the benefit of this treatmen...

Descripción completa

Detalles Bibliográficos
Autores principales: Cepparulo, Pasquale, Cuomo, Ornella, Vinciguerra, Antonio, Torelli, Monica, Annunziato, Lucio, Pignataro, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580415/
https://www.ncbi.nlm.nih.gov/pubmed/34777204
http://dx.doi.org/10.3389/fneur.2021.736474
_version_ 1784596604039200768
author Cepparulo, Pasquale
Cuomo, Ornella
Vinciguerra, Antonio
Torelli, Monica
Annunziato, Lucio
Pignataro, Giuseppe
author_facet Cepparulo, Pasquale
Cuomo, Ornella
Vinciguerra, Antonio
Torelli, Monica
Annunziato, Lucio
Pignataro, Giuseppe
author_sort Cepparulo, Pasquale
collection PubMed
description To date, the only effective pharmacological treatment for ischemic stroke is limited to the clinical use of recombinant tissue plasminogen activator (rtPA), although endovascular therapy has also emerged as an effective treatment for acute ischemic stroke. Unfortunately, the benefit of this treatment is limited to a 4.5-h time window. Most importantly, the use of rtPA is contraindicated in the case of hemorrhagic stroke. Therefore, the identification of a reliable biomarker to distinguish hemorrhagic from ischemic stroke could provide several advantages, including an earlier diagnosis, a better treatment, and a faster decision on ruling out hemorrhage so that tPA may be administered earlier. microRNAs (miRNAs) are stable non-coding RNAs crucially involved in the downregulation of gene expression via mRNA cleavage or translational repression. In the present paper, taking advantage of three preclinical animal models of stroke, we compared the miRNA blood levels of animals subjected to permanent or transient middle cerebral artery occlusion (MCAO) or to collagenase-induced hemorrhagic stroke. Preliminarily, we examined the rat miRNome in the brain tissue of ischemic and sham-operated rats; then, we selected those miRNAs whose expression was significantly modulated after stroke to create a list of miRNAs potentially involved in stroke damage. These selected miRNAs were then evaluated at different time intervals in the blood of rats subjected to permanent or transient focal ischemia or to hemorrhagic stroke. We found that four miRNAs—miR-16-5p, miR-101a-3p, miR-218-5p, and miR-27b-3p—were significantly upregulated in the plasma of rats 3 h after permanent MCAO, whereas four other different miRNAs—miR-150-5p, let-7b-5p, let-7c-5p, and miR-181b-5p—were selectively upregulated by collagenase-induced hemorrhagic stroke. Collectively, our study identified some selective miRNAs expressed in the plasma of hemorrhagic rats and pointed out the importance of a precise time point measurement to render more reliable the use of miRNAs as stroke biomarkers.
format Online
Article
Text
id pubmed-8580415
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-85804152021-11-11 Hemorrhagic Stroke Induces a Time-Dependent Upregulation of miR-150-5p and miR-181b-5p in the Bloodstream Cepparulo, Pasquale Cuomo, Ornella Vinciguerra, Antonio Torelli, Monica Annunziato, Lucio Pignataro, Giuseppe Front Neurol Neurology To date, the only effective pharmacological treatment for ischemic stroke is limited to the clinical use of recombinant tissue plasminogen activator (rtPA), although endovascular therapy has also emerged as an effective treatment for acute ischemic stroke. Unfortunately, the benefit of this treatment is limited to a 4.5-h time window. Most importantly, the use of rtPA is contraindicated in the case of hemorrhagic stroke. Therefore, the identification of a reliable biomarker to distinguish hemorrhagic from ischemic stroke could provide several advantages, including an earlier diagnosis, a better treatment, and a faster decision on ruling out hemorrhage so that tPA may be administered earlier. microRNAs (miRNAs) are stable non-coding RNAs crucially involved in the downregulation of gene expression via mRNA cleavage or translational repression. In the present paper, taking advantage of three preclinical animal models of stroke, we compared the miRNA blood levels of animals subjected to permanent or transient middle cerebral artery occlusion (MCAO) or to collagenase-induced hemorrhagic stroke. Preliminarily, we examined the rat miRNome in the brain tissue of ischemic and sham-operated rats; then, we selected those miRNAs whose expression was significantly modulated after stroke to create a list of miRNAs potentially involved in stroke damage. These selected miRNAs were then evaluated at different time intervals in the blood of rats subjected to permanent or transient focal ischemia or to hemorrhagic stroke. We found that four miRNAs—miR-16-5p, miR-101a-3p, miR-218-5p, and miR-27b-3p—were significantly upregulated in the plasma of rats 3 h after permanent MCAO, whereas four other different miRNAs—miR-150-5p, let-7b-5p, let-7c-5p, and miR-181b-5p—were selectively upregulated by collagenase-induced hemorrhagic stroke. Collectively, our study identified some selective miRNAs expressed in the plasma of hemorrhagic rats and pointed out the importance of a precise time point measurement to render more reliable the use of miRNAs as stroke biomarkers. Frontiers Media S.A. 2021-10-27 /pmc/articles/PMC8580415/ /pubmed/34777204 http://dx.doi.org/10.3389/fneur.2021.736474 Text en Copyright © 2021 Cepparulo, Cuomo, Vinciguerra, Torelli, Annunziato and Pignataro. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Cepparulo, Pasquale
Cuomo, Ornella
Vinciguerra, Antonio
Torelli, Monica
Annunziato, Lucio
Pignataro, Giuseppe
Hemorrhagic Stroke Induces a Time-Dependent Upregulation of miR-150-5p and miR-181b-5p in the Bloodstream
title Hemorrhagic Stroke Induces a Time-Dependent Upregulation of miR-150-5p and miR-181b-5p in the Bloodstream
title_full Hemorrhagic Stroke Induces a Time-Dependent Upregulation of miR-150-5p and miR-181b-5p in the Bloodstream
title_fullStr Hemorrhagic Stroke Induces a Time-Dependent Upregulation of miR-150-5p and miR-181b-5p in the Bloodstream
title_full_unstemmed Hemorrhagic Stroke Induces a Time-Dependent Upregulation of miR-150-5p and miR-181b-5p in the Bloodstream
title_short Hemorrhagic Stroke Induces a Time-Dependent Upregulation of miR-150-5p and miR-181b-5p in the Bloodstream
title_sort hemorrhagic stroke induces a time-dependent upregulation of mir-150-5p and mir-181b-5p in the bloodstream
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580415/
https://www.ncbi.nlm.nih.gov/pubmed/34777204
http://dx.doi.org/10.3389/fneur.2021.736474
work_keys_str_mv AT cepparulopasquale hemorrhagicstrokeinducesatimedependentupregulationofmir1505pandmir181b5pinthebloodstream
AT cuomoornella hemorrhagicstrokeinducesatimedependentupregulationofmir1505pandmir181b5pinthebloodstream
AT vinciguerraantonio hemorrhagicstrokeinducesatimedependentupregulationofmir1505pandmir181b5pinthebloodstream
AT torellimonica hemorrhagicstrokeinducesatimedependentupregulationofmir1505pandmir181b5pinthebloodstream
AT annunziatolucio hemorrhagicstrokeinducesatimedependentupregulationofmir1505pandmir181b5pinthebloodstream
AT pignatarogiuseppe hemorrhagicstrokeinducesatimedependentupregulationofmir1505pandmir181b5pinthebloodstream