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Connexin Hemichannel Blockade Is Neuroprotective after Asphyxia in Preterm Fetal Sheep
Asphyxia around the time of preterm birth is associated with neurodevelopmental disability. In this study, we tested the hypothesis that blockade of connexin hemichannels would improve recovery of brain activity and reduce cell loss after asphyxia in preterm fetal sheep. Asphyxia was induced by 25 m...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035262/ https://www.ncbi.nlm.nih.gov/pubmed/24865217 http://dx.doi.org/10.1371/journal.pone.0096558 |
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author | Davidson, Joanne O. Drury, Paul P. Green, Colin R. Nicholson, Louise F. Bennet, Laura Gunn, Alistair J. |
author_facet | Davidson, Joanne O. Drury, Paul P. Green, Colin R. Nicholson, Louise F. Bennet, Laura Gunn, Alistair J. |
author_sort | Davidson, Joanne O. |
collection | PubMed |
description | Asphyxia around the time of preterm birth is associated with neurodevelopmental disability. In this study, we tested the hypothesis that blockade of connexin hemichannels would improve recovery of brain activity and reduce cell loss after asphyxia in preterm fetal sheep. Asphyxia was induced by 25 min of complete umbilical cord occlusion in preterm fetal sheep (103–104 d gestational age). Connexin hemichannels were blocked by intracerebroventricular infusion of mimetic peptide starting 90 min after asphyxia at a concentration of 50 µM/h for one hour followed by 50 µM/24 hour for 24 hours (occlusion-peptide group, n = 6) or vehicle infusion for controls (occlusion-vehicle group, n = 7). Peptide infusion was associated with earlier recovery of electroencephalographic power after asphyxia compared to occlusion-vehicle (p<0.05), with reduced neuronal loss in the caudate and putamen (p<0.05), but not in the hippocampus. In the intragyral and periventricular white matter, peptide administration was associated with an increase in total oligodendrocyte numbers (p<0.05) and immature/mature oligodendrocytes compared to occlusion-vehicle (p<0.05), with a significant increase in proliferation (p<0.05). Connexin hemichannel blockade was neuroprotective and reduced oligodendrocyte death and improved recovery of oligodendrocyte maturation in preterm fetuses after asphyxia. |
format | Online Article Text |
id | pubmed-4035262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40352622014-06-02 Connexin Hemichannel Blockade Is Neuroprotective after Asphyxia in Preterm Fetal Sheep Davidson, Joanne O. Drury, Paul P. Green, Colin R. Nicholson, Louise F. Bennet, Laura Gunn, Alistair J. PLoS One Research Article Asphyxia around the time of preterm birth is associated with neurodevelopmental disability. In this study, we tested the hypothesis that blockade of connexin hemichannels would improve recovery of brain activity and reduce cell loss after asphyxia in preterm fetal sheep. Asphyxia was induced by 25 min of complete umbilical cord occlusion in preterm fetal sheep (103–104 d gestational age). Connexin hemichannels were blocked by intracerebroventricular infusion of mimetic peptide starting 90 min after asphyxia at a concentration of 50 µM/h for one hour followed by 50 µM/24 hour for 24 hours (occlusion-peptide group, n = 6) or vehicle infusion for controls (occlusion-vehicle group, n = 7). Peptide infusion was associated with earlier recovery of electroencephalographic power after asphyxia compared to occlusion-vehicle (p<0.05), with reduced neuronal loss in the caudate and putamen (p<0.05), but not in the hippocampus. In the intragyral and periventricular white matter, peptide administration was associated with an increase in total oligodendrocyte numbers (p<0.05) and immature/mature oligodendrocytes compared to occlusion-vehicle (p<0.05), with a significant increase in proliferation (p<0.05). Connexin hemichannel blockade was neuroprotective and reduced oligodendrocyte death and improved recovery of oligodendrocyte maturation in preterm fetuses after asphyxia. Public Library of Science 2014-05-27 /pmc/articles/PMC4035262/ /pubmed/24865217 http://dx.doi.org/10.1371/journal.pone.0096558 Text en © 2014 Davidson et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Davidson, Joanne O. Drury, Paul P. Green, Colin R. Nicholson, Louise F. Bennet, Laura Gunn, Alistair J. Connexin Hemichannel Blockade Is Neuroprotective after Asphyxia in Preterm Fetal Sheep |
title | Connexin Hemichannel Blockade Is Neuroprotective after Asphyxia in Preterm Fetal Sheep |
title_full | Connexin Hemichannel Blockade Is Neuroprotective after Asphyxia in Preterm Fetal Sheep |
title_fullStr | Connexin Hemichannel Blockade Is Neuroprotective after Asphyxia in Preterm Fetal Sheep |
title_full_unstemmed | Connexin Hemichannel Blockade Is Neuroprotective after Asphyxia in Preterm Fetal Sheep |
title_short | Connexin Hemichannel Blockade Is Neuroprotective after Asphyxia in Preterm Fetal Sheep |
title_sort | connexin hemichannel blockade is neuroprotective after asphyxia in preterm fetal sheep |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035262/ https://www.ncbi.nlm.nih.gov/pubmed/24865217 http://dx.doi.org/10.1371/journal.pone.0096558 |
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