Isoflurane-induced neuronal degeneration: an evaluation in organotypic hippocampal slice cultures.
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.
Wise-Faberowski
Lisa
L
Departments of *Anesthesiology, †Neurobiology, and ‡Surgery, Duke University Medical Center, Durham, North Carolina; and §Department of Neurobiology, Loma Linda University, Loma Linda, California.
Zhang
Haito
H
Ing
Richard
R
Pearlstein
Robert D
RD
Warner
David S
DS
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
D018685:Anesthetics, Inhalation; D007530:Isoflurane