Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits

Vesna Jevtovic-Todorovic, Richard E. Hartman, Yukitoshi Izumi, Nicholas D. Benshoff, Krikor Dikranian, Charles F. Zorumski, John W. Olney, David F. Wozniak

Research output: Contribution to journalArticle

1375 Scopus citations

Abstract

Recently it was demonstrated that exposure of the developing brain during the period of synaptogenesis to drugs that block NMDA glutamate receptors or drugs that potentiate GABAA receptors can trigger widespread apoptotic neurodegeneration. All currently used general anesthetic agents have either NMDA receptor-blocking or GABAA receptor-enhancing properties. To induce or maintain a surgical plane of anesthesia, it is common practice in pediatric or obstetrical medicine to use agents from these two classes in combination. Therefore, the question arises whether this practice entails significant risk of inducing apoptotic neurodegeneration in the developing human brain. To begin to address this problem, we have administered to 7-d-old infant rats a combination of drugs commonly used in pediatric anesthesia (midazolam, nitrous oxide, and isoflurane) in doses sufficient to maintain a surgical plane of anesthesia for 6 hr, and have observed that this causes widespread apoptotic neurodegeneration in the developing brain, deficits in hippocampal synaptic function, and persistent memory/learning impairments.

Original languageEnglish
Pages (from-to)876-882
Number of pages7
JournalJournal of Neuroscience
Volume23
Issue number3
StatePublished - Feb 1 2003

Keywords

  • Apoptosis
  • GABA agonists
  • Isoflurane
  • Midazolam
  • NMDA antagonists
  • Nitrous oxide

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