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Cell age-specific vulnerability of neurons to anesthetic toxicity : Anesthetic Neurotoxicity
Author(s):
Rylon D. Hofacer
,
Meng Deng
,
Christopher G. Ward
,
Bernadin Joseph
1
,
Elizabeth A. Hughes
1
,
Connie Jiang
1
,
Steve C. Danzer
,
Andreas W. Loepke
Publication date
(Electronic):
June 05 2013
Journal:
Annals of Neurology
Publisher:
Wiley
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PubMed
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Abstract
Anesthetics have been linked to widespread neuronal cell death in neonatal animals. Epidemiological human studies have associated early childhood anesthesia with long-term neurobehavioral abnormalities, raising substantial concerns that anesthetics may cause similar cell death in young children. However, key aspects of the phenomenon remain unclear, such as why certain neurons die, whereas immediately adjacent neurons are seemingly unaffected, and why the immature brain is exquisitely vulnerable, whereas the mature brain seems resistant. Elucidating these questions is critical for assessing the phenomenon's applicability to humans, defining the susceptible age, predicting vulnerable neuronal populations, and devising mitigating strategies. This study examines the effects of anesthetic exposure on late- and adult-generated neurons in newborn, juvenile, and adult mice, and characterizes vulnerable cells using birth-dating and immunohistochemical techniques. We identify a critical period of cellular developmental during which neurons are susceptible to anesthesia-induced apoptosis. Importantly, we demonstrate that anesthetic neurotoxicity can extend into adulthood in brain regions with ongoing neurogenesis, such as dentate gyrus and olfactory bulb. Our findings suggest that anesthetic vulnerability reflects the age of the neuron, not the age of the organism, and therefore may potentially not only be relevant to children but also to adults undergoing anesthesia. This observation further predicts differential heightened regional vulnerability to anesthetic neuroapoptosis to closely follow the distinct regional peaks in neurogenesis. This knowledge may help guide neurocognitive testing of specific neurological domains in humans following exposure to anesthesia, dependent on the individual's age during exposure. © 2013 American Neurological Association.
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Author and article information
Journal
Title:
Annals of Neurology
Abbreviated Title:
Ann Neurol.
Publisher:
Wiley
ISSN:
03645134
Publication date Created:
June 2013
Publication date (Print):
June 2013
Publication date (Electronic):
June 05 2013
Volume
: 73
Issue
: 6
Pages
: 695-704
Affiliations
[
1
]
Department of Anesthesiology; Cincinnati Children's Hospital Medical Center; Cincinnati; OH
Article
DOI:
10.1002/ana.23892
PubMed ID:
23526697
SO-VID:
de7acaf1-4900-43fd-bf7c-b089d64cf631
Copyright ©
© 2013
License:
http://doi.wiley.com/10.1002/tdm_license_1.1
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