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Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain

Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthet...

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Autores principales: Noguchi, Kevin K., Johnson, Stephen A., Manzella, Francesca M., Masuoka, Kobe L., Williams, Sasha L., Martin, Lauren D., Dissen, Gregory A., Ikonomidou, Chrysanthy, Schenning, Katie J., Olney, John W., Brambrink, Ansgar M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871879/
https://www.ncbi.nlm.nih.gov/pubmed/29593226
http://dx.doi.org/10.1038/s41598-018-23560-7
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author Noguchi, Kevin K.
Johnson, Stephen A.
Manzella, Francesca M.
Masuoka, Kobe L.
Williams, Sasha L.
Martin, Lauren D.
Dissen, Gregory A.
Ikonomidou, Chrysanthy
Schenning, Katie J.
Olney, John W.
Brambrink, Ansgar M.
author_facet Noguchi, Kevin K.
Johnson, Stephen A.
Manzella, Francesca M.
Masuoka, Kobe L.
Williams, Sasha L.
Martin, Lauren D.
Dissen, Gregory A.
Ikonomidou, Chrysanthy
Schenning, Katie J.
Olney, John W.
Brambrink, Ansgar M.
author_sort Noguchi, Kevin K.
collection PubMed
description Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthetic drugs trigger apoptotic death of neurons and oligodendrocytes in developing mammalian brains. Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in developing nonhuman primate brains. Fetal macaques (n = 7–8/group), at a neurodevelopmental age comparable to premature human infants, were exposed in utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3 fold for neurons and 3.4 fold for oligodendrocytes compared to control brains. Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to control levels but did not augment oligoapoptosis. Neuronal death was particularly pronounced in the basal ganglia and cerebellum. Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis. Caffeine markedly augments neurotoxicity of isoflurane in the fetal macaque brain and challenges the assumption that caffeine is safe for premature infants.
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spelling pubmed-58718792018-04-02 Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain Noguchi, Kevin K. Johnson, Stephen A. Manzella, Francesca M. Masuoka, Kobe L. Williams, Sasha L. Martin, Lauren D. Dissen, Gregory A. Ikonomidou, Chrysanthy Schenning, Katie J. Olney, John W. Brambrink, Ansgar M. Sci Rep Article Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthetic drugs trigger apoptotic death of neurons and oligodendrocytes in developing mammalian brains. Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in developing nonhuman primate brains. Fetal macaques (n = 7–8/group), at a neurodevelopmental age comparable to premature human infants, were exposed in utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3 fold for neurons and 3.4 fold for oligodendrocytes compared to control brains. Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to control levels but did not augment oligoapoptosis. Neuronal death was particularly pronounced in the basal ganglia and cerebellum. Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis. Caffeine markedly augments neurotoxicity of isoflurane in the fetal macaque brain and challenges the assumption that caffeine is safe for premature infants. Nature Publishing Group UK 2018-03-28 /pmc/articles/PMC5871879/ /pubmed/29593226 http://dx.doi.org/10.1038/s41598-018-23560-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Noguchi, Kevin K.
Johnson, Stephen A.
Manzella, Francesca M.
Masuoka, Kobe L.
Williams, Sasha L.
Martin, Lauren D.
Dissen, Gregory A.
Ikonomidou, Chrysanthy
Schenning, Katie J.
Olney, John W.
Brambrink, Ansgar M.
Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain
title Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain
title_full Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain
title_fullStr Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain
title_full_unstemmed Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain
title_short Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain
title_sort caffeine augments anesthesia neurotoxicity in the fetal macaque brain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871879/
https://www.ncbi.nlm.nih.gov/pubmed/29593226
http://dx.doi.org/10.1038/s41598-018-23560-7
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