ArticleScientific reports2018
Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 14 citations in OpenAlex.
- Exploratory bidirectional Mendelian randomisation analysis of cerebrospinal fluid metabolites associated with cerebral palsy and epilepsy.BMJ paediatrics open · 2026Article
- Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: an overview of recent findings.Neural regeneration research · 2024Article
- Synthetic neuroactive steroids as new sedatives and anaesthetics: Back to the future.Journal of neuroendocrinology · 2022Review
- Dietary Caffeine Synergizes Adverse Peripheral and Central Responses to Anesthesia in Malignant Hyperthermia Susceptible Mice.Molecular pharmacology · 2020Article
- Current Evidence on Cell Death in Preterm Brain Injury in Human and Preclinical Models.Frontiers in cell and developmental biology · 2020Review
- Quantitative ultrasound and apoptotic death in the neonatal primate brain.Neurobiology of disease · 2019Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.