title: Isoflurane-induced neuronal degeneration: an evaluation in organotypic hippocampal slice cultures.
abstract: Prolonged exposure of postnatal day (PND) 7 rat pups to anesthetics, which act via N-methyl-D-aspartate antagonism and/or gamma-amino butyric acid enhancement, causes neurodegeneration and persistent behavioral deficits. We studied these findings in vitro and determined whether the age of rat pups used for study or duration of anesthetic exposure modulates resultant neurodegeneration. Organotypic hippocampal slices (OHSs) were prepared from rat pups on PNDs 4, 7, and 14 and cultured 7 or 14 days in vitro. The slices were exposed to 1.5% isoflurane or fresh gas for durations of 1, 3, or 5 h. Hippocampal CA1, CA3, and dentate gyrus neuronal survival was assessed 3 days later. Neuronal cell death was greatest in OHSs prepared from PND 7 rat pups (P < 0.001) and was most evident after 5 h exposure to isoflurane (P < 0.001). By eliminating variables such as hemodynamics, nutrition, oxygenation, and carbon dioxide elimination, this in vitro investigation supports both an age- and duration-dependent relationship between 1.5% isoflurane exposure and perinatal neuronal death.
authors.affiliation: Departments of *Anesthesiology, †Neurobiology, and ‡Surgery, Duke University Medical Center, Durham, North Carolina; and §Department of Neurobiology, Loma Linda University, Loma Linda, California.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wise-Faberowski
authors.forename: Haito
authors.initials: H
authors.lastname: Zhang
authors.forename: Richard
authors.initials: R
authors.lastname: Ing
authors.forename: Robert D
authors.initials: RD
authors.lastname: Pearlstein
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D018891:Dentate Gyrus / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D017403:In Situ Hybridization; D007530:Isoflurane / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane