Early Exposure to General Anesthesia Causes Significant Neuronal Deletion in the Developing Rat Brain

Frequent exposure of children to general anesthesia is common practice in modern medicine. Although previously unrecognized, recent in vitro and in vivo animal studies suggest that exposure to clinically relevant general anesthetics at the peak of brain development could be detrimental to immature m...

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2007-12, Vol.1122 (1), p.69-82
Main Authors: NIKIZAD, H., YON, J-H., CARTER, L. B., JEVTOVIC-TODOROVIC, V.
Format: Article
Language:English
Subjects:
amphiphysin
Anesthetics, Inhalation - adverse effects
Animals
Animals, Newborn
Apoptosis - drug effects
Brain - cytology
Brain - growth & development
CaM kinase II
Gene Expression Regulation, Developmental - drug effects
isoflurane
midazolam
Nerve Tissue Proteins - metabolism
Neurons - drug effects
nitrous oxide
Rats
Rats, Sprague-Dawley
SNAP-25
synaptobrevin
synaptophysin
Time Factors
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Summary:Frequent exposure of children to general anesthesia is common practice in modern medicine. Although previously unrecognized, recent in vitro and in vivo animal studies suggest that exposure to clinically relevant general anesthetics at the peak of brain development could be detrimental to immature mammalian neurons, as demonstrated by massive and widespread apoptotic neurodegeneration. The survival of the developing neurons presumably depends on proper and timely formation of synapses, for which synaptic proteins (e.g., synaptophysin, synaptobrevin, amphiphysin, synaptosomal‐associated protein 25 [SNAP‐25], and Ca2+/calmodulin‐dependent protein kinase II [CaM kinase II]) are crucially important. Overinhibition of developing neurons impairs synaptic protein function and activity‐induced synaptic plasticity, which could in turn result in permanent neuronal loss. To examine the effects of general anesthesia, the pharmacological agents known to cause extensive neuronal inhibition, on synaptic proteins, and neuronal survival at the peak of synaptogenesis, we exposed 7‐day‐old rat pups to general anesthesia (midazolam, 9 mg/kg of body weight, subcutaneously, followed by 6 h of nitrous oxide 75 vol% and isoflurane 0.75 vol%). We found that this general anesthesia causes permanent neuronal deletion in the most vulnerable brain regions—the cerebral cortex and the thalamus—while transiently modulating protein levels of synaptophysin, synaptobrevin, amphiphysin, SNAP‐25, and CaM kinase II.
ISSN:0077-8923
1749-6632
1930-6547
DOI:10.1196/annals.1403.005