Sevoflurane neurotoxicity in neonatal rats is related to an increase in the GABAAR α1/GABAAR α2 ratio

Exposure of neonatal rat to sevoflurane leads to neurodegeneration and deficits of spatial learning and memory in adulthood. However, the underlying mechanisms remain unclear. The type A gamma-aminobutyric acid receptor (GABA(A)R) is a target receptor for sevoflurane. The present study intends to investigate the changes in GABA(A)R alpha 1/alpha 2 expression and its relationship with the neurotoxicity effect due to sevoflurane in neonatal rats. After a dose-response curve was constructed to determine minimum alveolar concentration (MAC) and safety was guaranteed in our 7-day-old neonatal rat pup mode, we conducted two studies among the following groups: (A) the control group; (B) the sham anesthesia group; and (C) the sevoflurane anesthesia group and all three groups were treated in the same way as the model. First, poly(ADP-ribose) polymerase-1 protein (PARP-1) expression was determined in the different brain areas at 6 hr after anesthesia. Second, the expression of PARP-1 and GABA(A)R alpha 1/GABA(A)R alpha 2 in the hippocampus area was tested by Western blotting at 6 hr, 24 hr, and 72 hr after anesthesia in all three groups. After 4 hr, with 0.8 MAC (2.1%) sevoflurane anesthesia, the PARP-1 expression was significantly higher in the hippocampus than the other brain areas (p < .05). Compared with Groups A and B, the expression of PARP-1 in the hippocampus of Group C significantly increased at 6 hr after sevoflurane exposure (216% +/- 15%, p < .05), and the ratio of the alpha 1/alpha 2 subunit of GABA(A)R surged at 6 hr (126% +/- 6%), 24 hr (127% +/- 8%), and 72 hr (183% +/- 22%) after sevoflurane exposure in the hippocampus (p < .05). Our study showed that sevoflurane exposure of 0.8 MAC (2.1%)/4 hr was a suitable model for 7-day-old rats. And the exposure to sevoflurane could induce the apoptosis of neurons in the early stage, which may be related to the transmission from GABA(A)R alpha 2 toGABA(A)R alpha 1.