The Effect of Sevoflurane on Neuronal Degeneration and GABAA Subunit Composition in a Developing Rat Model of Organotypic Hippocampal Slice Cultures

Abstract

The GABAA receptor subunit composition undergoes a switch from a predominantly α2 to a predominantly α1 around postnatal day (PND) 7 in a rat pup. This developmental switch in the GABAA receptor subunit composition changes the kinetics and pharmacologic properties of the GABAA receptor. Using a developmental organotypic hippocampal slice model, we hypothesized that the developmental changes in the GABAA receptor subunit composition may promote neurodegeneration after exposure to sevoflurane.

Organotypic 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 GABAA receptor subunit composition were assessed immediately, 24 and 72 hours after exposure and compared with air.

Early 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 α1 and/or increase in the α2 subunit composition promoted cell survival in the PND 4 and 7 OHS. On PND14, cell survival was promoted by an increase in the α1 subunit composition.

This in vitro investigation supports an age-dependent and GABAA receptor subunit composition relationship between 2.0% sevoflurane exposure and cell death.