title: From the Cover: Volatile Anesthetics Transiently Disrupt Neuronal Development in Neonatal Rats.
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: Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104.
authors: Julie K
authors: JK
authors: Drobish
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104.
authors: Zoe S
authors: ZS
authors: Gan
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104.
authors: Amanda D
authors: AD
authors: Cornfeld
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104 maryellen.eckenhoff@uphs.upenn.edu.
authors: Maryellen F
authors: MF
authors: Eckenhoff
mesh_terms: D000367:Age Factors; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D000077335:Desflurane; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000633:toxicity; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008738:Methyl Ethers / Q000633:toxicity*; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane
keywords: anesthesia; development; learning and memory.; neonatal; neurogenesis; neurotoxicity