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Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome

RNA-binding motif protein 3 is a molecular marker of hypothermia that has proved neuroprotective in neurodegenerative disease models. However, its relationship to the well-recognized therapeutic effect of hypothermia in ischaemic stroke had not been studied. In this work, the expression of RNA-bindi...

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Autores principales: Ávila-Gómez, Paulo, Vieites-Prado, Alba, Dopico-López, Antonio, Bashir, Saima, Fernández-Susavila, Héctor, Gubern, Carme, Pérez-Mato, María, Correa-Paz, Clara, Iglesias-Rey, Ramón, Sobrino, Tomás, Bustamante, Alejandro, Wellmann, Sven, Montaner, Joan, Serena, Joaquín, Castillo, José, Hervella, Pablo, Campos, Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869850/
https://www.ncbi.nlm.nih.gov/pubmed/33585816
http://dx.doi.org/10.1093/braincomms/fcaa078
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author Ávila-Gómez, Paulo
Vieites-Prado, Alba
Dopico-López, Antonio
Bashir, Saima
Fernández-Susavila, Héctor
Gubern, Carme
Pérez-Mato, María
Correa-Paz, Clara
Iglesias-Rey, Ramón
Sobrino, Tomás
Bustamante, Alejandro
Wellmann, Sven
Montaner, Joan
Serena, Joaquín
Castillo, José
Hervella, Pablo
Campos, Francisco
author_facet Ávila-Gómez, Paulo
Vieites-Prado, Alba
Dopico-López, Antonio
Bashir, Saima
Fernández-Susavila, Héctor
Gubern, Carme
Pérez-Mato, María
Correa-Paz, Clara
Iglesias-Rey, Ramón
Sobrino, Tomás
Bustamante, Alejandro
Wellmann, Sven
Montaner, Joan
Serena, Joaquín
Castillo, José
Hervella, Pablo
Campos, Francisco
author_sort Ávila-Gómez, Paulo
collection PubMed
description RNA-binding motif protein 3 is a molecular marker of hypothermia that has proved neuroprotective in neurodegenerative disease models. However, its relationship to the well-recognized therapeutic effect of hypothermia in ischaemic stroke had not been studied. In this work, the expression of RNA-binding motif protein 3 was investigated in ischaemic animal models subjected to systemic and focal brain hypothermia, specifically the effects of RNA-binding motif protein 3 silencing and overexpression on ischaemic lesions. Moreover, the association of RNA-binding motif protein 3 levels with body temperature and clinical outcome was evaluated in two independent cohorts of acute ischaemic stroke patients (n = 215); these levels were also determined in a third cohort of 31 patients derived from the phase III EuroHYP-1 trial of therapeutic cooling in ischaemic stroke. The preclinical data confirmed the increase of brain RNA-binding motif protein 3 levels in ischaemic animals subjected to systemic and focal hypothermia; this increase was selectively higher in the cooled hemisphere of animals undergoing focal brain hypothermia, thus confirming the direct effect of hypothermia on RNA-binding motif protein 3 expression, while RNA-binding motif protein 3 up-regulation in ischaemic brain regions led to functional recovery. Clinically, patients with body temperature <37.5°C in the first two cohorts had higher RNA-binding motif protein 3 values at 24 h and good outcome at 3 months post-ischaemic stroke, while RNA-binding motif protein 3 levels in the cooled third cohort tended to exceed those in placebo-treated patients. These results make RNA-binding motif protein 3 a molecular marker associated with the effect of hypothermia in ischaemic stroke and suggest its potential application as a promising protective target.
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spelling pubmed-78698502021-02-11 Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome Ávila-Gómez, Paulo Vieites-Prado, Alba Dopico-López, Antonio Bashir, Saima Fernández-Susavila, Héctor Gubern, Carme Pérez-Mato, María Correa-Paz, Clara Iglesias-Rey, Ramón Sobrino, Tomás Bustamante, Alejandro Wellmann, Sven Montaner, Joan Serena, Joaquín Castillo, José Hervella, Pablo Campos, Francisco Brain Commun Original Article RNA-binding motif protein 3 is a molecular marker of hypothermia that has proved neuroprotective in neurodegenerative disease models. However, its relationship to the well-recognized therapeutic effect of hypothermia in ischaemic stroke had not been studied. In this work, the expression of RNA-binding motif protein 3 was investigated in ischaemic animal models subjected to systemic and focal brain hypothermia, specifically the effects of RNA-binding motif protein 3 silencing and overexpression on ischaemic lesions. Moreover, the association of RNA-binding motif protein 3 levels with body temperature and clinical outcome was evaluated in two independent cohorts of acute ischaemic stroke patients (n = 215); these levels were also determined in a third cohort of 31 patients derived from the phase III EuroHYP-1 trial of therapeutic cooling in ischaemic stroke. The preclinical data confirmed the increase of brain RNA-binding motif protein 3 levels in ischaemic animals subjected to systemic and focal hypothermia; this increase was selectively higher in the cooled hemisphere of animals undergoing focal brain hypothermia, thus confirming the direct effect of hypothermia on RNA-binding motif protein 3 expression, while RNA-binding motif protein 3 up-regulation in ischaemic brain regions led to functional recovery. Clinically, patients with body temperature <37.5°C in the first two cohorts had higher RNA-binding motif protein 3 values at 24 h and good outcome at 3 months post-ischaemic stroke, while RNA-binding motif protein 3 levels in the cooled third cohort tended to exceed those in placebo-treated patients. These results make RNA-binding motif protein 3 a molecular marker associated with the effect of hypothermia in ischaemic stroke and suggest its potential application as a promising protective target. Oxford University Press 2020-06-04 /pmc/articles/PMC7869850/ /pubmed/33585816 http://dx.doi.org/10.1093/braincomms/fcaa078 Text en © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Article
Ávila-Gómez, Paulo
Vieites-Prado, Alba
Dopico-López, Antonio
Bashir, Saima
Fernández-Susavila, Héctor
Gubern, Carme
Pérez-Mato, María
Correa-Paz, Clara
Iglesias-Rey, Ramón
Sobrino, Tomás
Bustamante, Alejandro
Wellmann, Sven
Montaner, Joan
Serena, Joaquín
Castillo, José
Hervella, Pablo
Campos, Francisco
Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome
title Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome
title_full Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome
title_fullStr Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome
title_full_unstemmed Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome
title_short Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome
title_sort cold stress protein rbm3 responds to hypothermia and is associated with good stroke outcome
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869850/
https://www.ncbi.nlm.nih.gov/pubmed/33585816
http://dx.doi.org/10.1093/braincomms/fcaa078
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