文章基本信息

标题：Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain
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作者：Kevin K. Noguchi ; Stephen A. Johnson ; Francesca M. Manzella 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：5302
DOI：10.1038/s41598-018-23560-7
语种：English
出版社：Springer Nature
摘要：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.