• Estee Piehl, Lisa Foley, Max Barron, Chris D'Ardenne, Paul Guillod, and Lisa Wise-Faberowski.
• University of Colorado, Denver, CO, USA.
• J Neurosurg Anesthesiol. 2010 Jul 1; 22 (3): 220-9.

ObjectiveThe GABA(A) receptor subunit composition undergoes a switch from a predominantly alpha2 to a predominantly alpha1 around postnatal day (PND) 7 in a rat pup. This developmental switch in the GABA(A) receptor subunit composition changes the kinetics and pharmacologic properties of the GABA(A) receptor. Using a developmental organotypic hippocampal slice model, we hypothesized that the developmental changes in the GABA(A) receptor subunit composition may promote neurodegeneration after exposure to sevoflurane.DesignOrganotypic hippocampal slices (OHS) were prepared from rat pups on PND 4, 7, and 14 and exposed to 2.0% sevoflurane or air for 5 hours. Hippocampal CA1, CA3, and dentate gyrus neuronal survival and GABA(A) receptor subunit composition were assessed immediately, 24 and 72 hours after exposure and compared with air.Measurements And ResultsEarly cell death immediately after exposure to sevoflurane was statistically significant in the PND14 (P<0.001). At 24 hours, cell death was not significant for any PND age-examined OHS. However, at 72 hours, cell death was significant in the OHS prepared from the PND7 and 4 rat pups (P<0.001). In further analysis, either a decrease in the alpha1 and/or increase in the alpha2 subunit composition promoted cell survival in the PND 4 and 7 OHS. On PND14, cell survival was promoted by an increase in the alpha1 subunit composition.ConclusionsThis in vitro investigation supports an age-dependent and GABA(A) receptor subunit composition relationship between 2.0% sevoflurane exposure and cell death.

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