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Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury

In human beings the immature brain is highly plastic and depending on the stage of gestation is particularly vulnerable to a range of insults that if sufficiently severe, can result in long-term motor, cognitive and behavioral impairment. With improved neonatal care, the incidence of major motor def...

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Autores principales: Cho, Kenta Hyeon Tae, Xu, Bing, Blenkiron, Cherie, Fraser, Mhoyra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447777/
https://www.ncbi.nlm.nih.gov/pubmed/30984006
http://dx.doi.org/10.3389/fphys.2019.00227
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author Cho, Kenta Hyeon Tae
Xu, Bing
Blenkiron, Cherie
Fraser, Mhoyra
author_facet Cho, Kenta Hyeon Tae
Xu, Bing
Blenkiron, Cherie
Fraser, Mhoyra
author_sort Cho, Kenta Hyeon Tae
collection PubMed
description In human beings the immature brain is highly plastic and depending on the stage of gestation is particularly vulnerable to a range of insults that if sufficiently severe, can result in long-term motor, cognitive and behavioral impairment. With improved neonatal care, the incidence of major motor deficits such as cerebral palsy has declined with prematurity. Unfortunately, however, milder forms of injury characterized by diffuse non-cystic white matter lesions within the periventricular region and surrounding white matter, involving loss of oligodendrocyte progenitors and subsequent axonal hypomyelination as the brain matures have not. Existing therapeutic options for treatment of preterm infants have proved inadequate, partly owing to an incomplete understanding of underlying post-injury cellular and molecular changes that lead to poor neurodevelopmental outcomes. This has reinforced the need to improve our understanding of brain plasticity, explore novel solutions for the development of protective strategies, and identify biomarkers. Compelling evidence exists supporting the involvement of microRNAs (miRNAs), a class of small non-coding RNAs, as important post-transcriptional regulators of gene expression with functions including cell fate specification and plasticity of synaptic connections. Importantly, miRNAs are differentially expressed following brain injury, and can be packaged within exosomes/extracellular vesicles, which play a pivotal role in assuring their intercellular communication and passage across the blood–brain barrier. Indeed, an increasing number of investigations have examined the roles of specific miRNAs following injury and regeneration and it is apparent that this field of research could potentially identify protective therapeutic strategies to ameliorate perinatal brain injury. In this review, we discuss the most recent findings of some important miRNAs in relation to the development of the brain, their dysregulation, functions and regulatory roles following brain injury, and discuss how these can be targeted either as biomarkers of injury or neuroprotective agents.
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spelling pubmed-64477772019-04-12 Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury Cho, Kenta Hyeon Tae Xu, Bing Blenkiron, Cherie Fraser, Mhoyra Front Physiol Physiology In human beings the immature brain is highly plastic and depending on the stage of gestation is particularly vulnerable to a range of insults that if sufficiently severe, can result in long-term motor, cognitive and behavioral impairment. With improved neonatal care, the incidence of major motor deficits such as cerebral palsy has declined with prematurity. Unfortunately, however, milder forms of injury characterized by diffuse non-cystic white matter lesions within the periventricular region and surrounding white matter, involving loss of oligodendrocyte progenitors and subsequent axonal hypomyelination as the brain matures have not. Existing therapeutic options for treatment of preterm infants have proved inadequate, partly owing to an incomplete understanding of underlying post-injury cellular and molecular changes that lead to poor neurodevelopmental outcomes. This has reinforced the need to improve our understanding of brain plasticity, explore novel solutions for the development of protective strategies, and identify biomarkers. Compelling evidence exists supporting the involvement of microRNAs (miRNAs), a class of small non-coding RNAs, as important post-transcriptional regulators of gene expression with functions including cell fate specification and plasticity of synaptic connections. Importantly, miRNAs are differentially expressed following brain injury, and can be packaged within exosomes/extracellular vesicles, which play a pivotal role in assuring their intercellular communication and passage across the blood–brain barrier. Indeed, an increasing number of investigations have examined the roles of specific miRNAs following injury and regeneration and it is apparent that this field of research could potentially identify protective therapeutic strategies to ameliorate perinatal brain injury. In this review, we discuss the most recent findings of some important miRNAs in relation to the development of the brain, their dysregulation, functions and regulatory roles following brain injury, and discuss how these can be targeted either as biomarkers of injury or neuroprotective agents. Frontiers Media S.A. 2019-03-28 /pmc/articles/PMC6447777/ /pubmed/30984006 http://dx.doi.org/10.3389/fphys.2019.00227 Text en Copyright © 2019 Cho, Xu, Blenkiron and Fraser. http://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 Physiology
Cho, Kenta Hyeon Tae
Xu, Bing
Blenkiron, Cherie
Fraser, Mhoyra
Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury
title Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury
title_full Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury
title_fullStr Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury
title_full_unstemmed Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury
title_short Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury
title_sort emerging roles of mirnas in brain development and perinatal brain injury
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447777/
https://www.ncbi.nlm.nih.gov/pubmed/30984006
http://dx.doi.org/10.3389/fphys.2019.00227
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