Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain

Kevin K. Noguchi, Stephen A. Johnson, Francesca M. Manzella, Kobe L. Masuoka, Sasha L. Williams, Lauren Drew Martin, Gregory Dissen, Chrysanthy Ikonomidou, Katie J. Schenning, John W. Olney, Ansgar Brambrink

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish (US)
    Article number5302
    JournalScientific Reports
    Volume8
    Issue number1
    DOIs
    StatePublished - Dec 1 2018

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    Macaca
    Caffeine
    Isoflurane
    Anesthesia
    Brain
    Premature Infants
    Oligodendroglia
    Apoptosis
    Respiratory System Agents
    Neonatology
    Neurons
    Drug and Narcotic Control
    Apnea
    Basal Ganglia
    Hypnotics and Sedatives
    Cerebellum
    Primates
    Anesthetics
    Research

    ASJC Scopus subject areas

    • General

    Cite this

    Noguchi, K. K., Johnson, S. A., Manzella, F. M., Masuoka, K. L., Williams, S. L., Martin, L. D., ... Brambrink, A. (2018). Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain. Scientific Reports, 8(1), [5302]. https://doi.org/10.1038/s41598-018-23560-7

    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 Drew; Dissen, Gregory; Ikonomidou, Chrysanthy; Schenning, Katie J.; Olney, John W.; Brambrink, Ansgar.

    In: Scientific Reports, Vol. 8, No. 1, 5302, 01.12.2018.

    Research output: Contribution to journalArticle

    Noguchi, KK, Johnson, SA, Manzella, FM, Masuoka, KL, Williams, SL, Martin, LD, Dissen, G, Ikonomidou, C, Schenning, KJ, Olney, JW & Brambrink, A 2018, 'Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain', Scientific Reports, vol. 8, no. 1, 5302. https://doi.org/10.1038/s41598-018-23560-7
    Noguchi KK, Johnson SA, Manzella FM, Masuoka KL, Williams SL, Martin LD et al. Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain. Scientific Reports. 2018 Dec 1;8(1). 5302. https://doi.org/10.1038/s41598-018-23560-7
    Noguchi, Kevin K. ; Johnson, Stephen A. ; Manzella, Francesca M. ; Masuoka, Kobe L. ; Williams, Sasha L. ; Martin, Lauren Drew ; Dissen, Gregory ; Ikonomidou, Chrysanthy ; Schenning, Katie J. ; Olney, John W. ; Brambrink, Ansgar. / Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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