Pre-treatment with a Xingnaojing preparation ameliorates sevoflurane-induced neuroapoptosis in the infant rat striatum

Xingnaojing (XNJ), is a standardized Chinese herbal medicine product derived from An Gong Niu Huang Pill. It may be involved in neuroprotection in a number of neurological disorders. Exposure to anesthetic agents during the brain growth spurt may trigger widespread neuroapoptosis in the developing brain. Thus the present study aimed to identify whether there was a neuroprotective effect of XNJ on anesthesia-induced neuroapoptosis. Seven-day-old rats received treatment with 2.1% sevoflurane for 6 h. Rat pups were injected intraperitoneally with 1 or 10 ml/kg XNJ at 0.2, 24 and 48 h prior to sevoflurane exposure. The striata of neonatal rats were collected following administration of anesthesia. Western blotting and immunohistochemistry were used to analyze the expression of activated caspase 3, Bax and phosphorylated protein kinase B (p-AKT) in the striatum. It was found that activated caspase 3 and Bax expression were upregulated in the striatum following sevoflurane treatment. Preconditioning with XNJ attenuated the neuronal apoptosis induced by sevoflurane in a dose-dependent manner. Anesthesia reduced the expression of p-AKT (phosphorylated at sites Thr308 and Ser473) and phosphorylated extracellular-regulated protein kinase (p-ERK) in the striatum. Pre-treatment with XNJ reversed the reduction in p-AKT, but not p-ERK expression. These data suggest that XNJ has an antiapoptotic effect against sevoflurane-induced cell loss in the striatum. It thus holds promise as a safe and effective neuroprotective agent. The action of XNJ on p-AKT may make a significant contribution to its neuroprotective effect.