Sevoflurane Induces Hippocampal Neuronal Apoptosis by Altering the Level of Neuropeptide Y in Neonatal Rats

Abstract

Numerous studies have shown that the inhaled general anesthetic sevoflurane imposes toxicity on the central nervous system during the developmental period but the underlying mechanisms remain unclear. Neuropeptide Y (NPY) was reported to have important neuroprotective effects, which can attenuate neuronal loss under pathological conditions. However, the effects of NPY on sevoflurane-induced hippocampal neuronal apoptosis have not been investigated. In this study, postnatal day 7 (PND7) Sprague–Dawley rats and primary cultured cells separated from hippocampi were exposed to sevoflurane (2.4% for 4 h) and the NPY expression levels after treatment were analyzed. Furthermore, neuronal apoptosis assay was conducted via immunofluorescence staining of cleaved caspase-3 and flow cytometry after exogenous NPY administration to PND7 rats as well as cultured hippocampal neurons to elucidate the role of NPY in sevoflurane-induced neurotoxicity. Our results showed the level of NPY gradually decreased within 24 h after sevoflurane exposure in both the hippocampus of PND7 rats and cultured hippocampal neurons, but not in cultured astrocytes. In the exogenous NPY pretreatment study, the proportion of cleaved caspase-3 positive cells in the CA1 region of the hippocampus was increased significantly at 24 h after sevoflurane treatment, while NPY pretreatment could reduce it. Similarly, NPY could also reverse the apoptogenic effect of sevoflurane on cultured neurons. Herein, our results showed that sevoflurane caused a significant decrease in NPY expression, whereas exogenous NPY supplementation could reduce sevoflurane-induced hippocampal neuronal apoptosis both in vivo and in vitro.