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From the Cover: Volatile Anesthetics Transiently Disrupt Neuronal Development in Neonatal Rats.
Toxicol Sci. 2016 12; 154(2):309-319.TS

Abstract

Volatile anesthetics can cause neuronal and glial toxicity in the developing mammalian brain, as well as long-term defects in learning and memory. The goals of this study were to compare anesthetics using a clinically relevant exposure paradigm, and to assess the anesthetic effects on hippocampal development and behavior. Our hypothesis was that volatile anesthetics disrupt hippocampal development, causing neurobehavioral defects later in life. Bromodeoxyuridine (BrdU) was administered to rats on postnatal day (P)1, and the rats were exposed to volatile anesthetics (isoflurane, sevoflurane, or desflurane) for 2 h on P2. On days P7 and P14, the BrdU-labeled cells were quantified in the hippocampal dentate gyrus using immunohistochemical assays and fluorescent microscopy. Caspase-3 positive cells were quantified on P2 to evaluate apoptosis. The remaining animals underwent behavioral testing at ages 6 weeks and 6 months, using the Morris Water Maze. Significantly fewer BrdU-positive cells were detected in the hippocampal dentate gyrus in both isoflurane and desflurane-treated animals compared with controls at P7, but there were no changes in cell numbers after sevoflurane exposure. Cell counts for all three anesthetics compared with controls were equivalent at P14. Isoflurane or desflurane exposure yielded slight differences in the behavioral tests at 6 weeks, but no differences at 6 months post-exposure. We conclude that a single 2-h exposure at P2 to either isoflurane or desflurane causes a transient disruption of hippocampal neuronal development with no significant detectable long-term effects on learning and memory, whereas the same exposure to sevoflurane has no effects.

Authors+Show Affiliations

Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104.Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104.Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104.Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104 maryellen.eckenhoff@uphs.upenn.edu.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

27562558

Citation

Drobish, Julie K., et al. "From the Cover: Volatile Anesthetics Transiently Disrupt Neuronal Development in Neonatal Rats." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 154, no. 2, 2016, pp. 309-319.
Drobish JK, Gan ZS, Cornfeld AD, et al. From the Cover: Volatile Anesthetics Transiently Disrupt Neuronal Development in Neonatal Rats. Toxicol Sci. 2016;154(2):309-319.
Drobish, J. K., Gan, Z. S., Cornfeld, A. D., & Eckenhoff, M. F. (2016). From the Cover: Volatile Anesthetics Transiently Disrupt Neuronal Development in Neonatal Rats. Toxicological Sciences : an Official Journal of the Society of Toxicology, 154(2), 309-319.
Drobish JK, et al. From the Cover: Volatile Anesthetics Transiently Disrupt Neuronal Development in Neonatal Rats. Toxicol Sci. 2016;154(2):309-319. PubMed PMID: 27562558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - From the Cover: Volatile Anesthetics Transiently Disrupt Neuronal Development in Neonatal Rats. AU - Drobish,Julie K, AU - Gan,Zoe S, AU - Cornfeld,Amanda D, AU - Eckenhoff,Maryellen F, Y1 - 2016/08/25/ PY - 2016/8/27/pubmed PY - 2018/1/18/medline PY - 2016/8/27/entrez KW - anesthesia KW - development KW - learning and memory. KW - neonatal KW - neurogenesis KW - neurotoxicity SP - 309 EP - 319 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol. Sci. VL - 154 IS - 2 N2 - Volatile anesthetics can cause neuronal and glial toxicity in the developing mammalian brain, as well as long-term defects in learning and memory. The goals of this study were to compare anesthetics using a clinically relevant exposure paradigm, and to assess the anesthetic effects on hippocampal development and behavior. Our hypothesis was that volatile anesthetics disrupt hippocampal development, causing neurobehavioral defects later in life. Bromodeoxyuridine (BrdU) was administered to rats on postnatal day (P)1, and the rats were exposed to volatile anesthetics (isoflurane, sevoflurane, or desflurane) for 2 h on P2. On days P7 and P14, the BrdU-labeled cells were quantified in the hippocampal dentate gyrus using immunohistochemical assays and fluorescent microscopy. Caspase-3 positive cells were quantified on P2 to evaluate apoptosis. The remaining animals underwent behavioral testing at ages 6 weeks and 6 months, using the Morris Water Maze. Significantly fewer BrdU-positive cells were detected in the hippocampal dentate gyrus in both isoflurane and desflurane-treated animals compared with controls at P7, but there were no changes in cell numbers after sevoflurane exposure. Cell counts for all three anesthetics compared with controls were equivalent at P14. Isoflurane or desflurane exposure yielded slight differences in the behavioral tests at 6 weeks, but no differences at 6 months post-exposure. We conclude that a single 2-h exposure at P2 to either isoflurane or desflurane causes a transient disruption of hippocampal neuronal development with no significant detectable long-term effects on learning and memory, whereas the same exposure to sevoflurane has no effects. SN - 1096-0929 UR - https://www.unboundmedicine.com/medline/citation/27562558/From_the_Cover:_Volatile_Anesthetics_Transiently_Disrupt_Neuronal_Development_in_Neonatal_Rats_ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfw164 DB - PRIME DP - Unbound Medicine ER -