Repeated neonatal isoflurane exposures in the mouse induce apoptotic degenerative changes in the brain and relatively mild long-term behavioral deficits

Scientific Reports
Susan E MaloneyDavid F Wozniak

Abstract

Epidemiological studies suggest exposures to anesthetic agents and/or sedative drugs (AASDs) in children under three years old, or pregnant women during the third trimester, may adversely affect brain development. Evidence suggests lengthy or repeated AASD exposures are associated with increased risk of neurobehavioral deficits. Animal models have been valuable in determining the type of acute damage in the developing brain induced by AASD exposures, as well as in elucidating long-term functional consequences. Few studies examining very early exposure to AASDs suggest this may be a critical period for inducing long-term functional consequences, but the impact of repeated exposures at these ages has not yet been assessed. To address this, we exposed mouse pups to a prototypical general anesthetic, isoflurane (ISO, 1.5% for 3 hr), at three early postnatal ages (P3, P5 and P7). We quantified the acute neuroapoptotic response to a single versus repeated exposure, and found age- and brain region-specific effects. We also found that repeated early exposures to ISO induced subtle, sex-specific disruptions to activity levels, motor coordination, anxiety-related behavior and social preference. Our findings provide evidence that repeated...Continue Reading

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Citations

Jun 20, 2019·Genes, Brain, and Behavior·Susan E MaloneyJoseph D Dougherty
Mar 3, 2020·Developmental Psychobiology·Daniil P AksenovAlexander Drobyshevsky
Mar 28, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Serdar DemirganAyşin Selcan
Jul 29, 2021·Nature Communications·Amanda M SmithTimothy J Ley

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