Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits
by
Jevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND,
Dikranian K, Zorumski CF, Olney JW, Wozniak DF.
Department of Anesthesiology,
University of Virginia Health System,
Charlottesville, Virginia 22908, USA.
vj3w@virginia.edu
J Neurosci. 2003 Feb 1;23(3):876-82


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 GABA(A) receptors can trigger widespread apoptotic neurodegeneration. All currently used general anesthetic agents have either NMDA receptor-blocking or GABA(A) 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.
People
Apoptosis
Anaesthesia
Nitrous oxide
Capnography
Inhaled anaesthetics
Molecular mechanisms
Chloroform anaesthesia
A thalamocortical switch?
Anaesthesia and the spinal chord
Consciousness, anaesthesia and anaesthetics
Drug-induced apoptotic neurodegeneration in the developing brain



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