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The Journal of Neuroscience, February 1, 2003, 23(3):876
Early Exposure to Common Anesthetic Agents Causes Widespread Neurodegeneration in the Developing Rat Brain and Persistent Learning Deficits
Vesna Jevtovic-Todorovic1, Richard E. Hartman2, Yukitoshi Izumi3, Nicholas D. Benshoff3, Krikor Dikranian3, Charles F. Zorumski3, John W. Olney3, and David F. Wozniak3 1 Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia 22908, and Departments of 2 Neurology and 3 Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110
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.
Key words: NMDA antagonists; GABA agonists; isoflurane; midazolam; nitrous oxide; apoptosis
Copyright © 2003 Society for Neuroscience 0270-6474/03/233876-07$05.00/0
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