Role of NR2B/ERK signaling in the neuroprotective effect of dexmedetomidine against sevoflurane induced neurological dysfunction in the developing rat brain

Abstract

Background Dexmedetomidine (DEX) is a new-generation, and has been widely applied in clinic. The present study confirmed the protective effect of DEX on sevoflurane induced learning and cognitive impairment and examined its underlying mechanism. Methods Sprague-Dawley rats were exposed to 0.85% sevoflurane for 6 h and injected with DEX in different dose. Morris water maze (MWM) test was performed to evaluate the learning and memory function of rats. Western blot was used for the measurement of protein levels. Results MWM results indicated that sevoflurane treatment increased the escape latency but reduced the time spent in original quadrant of rats. The protein levels of NR2B, phosphorylated ERK were significantly influenced by sevoflurane. Ifenprodil administration alleviated sevoflurane induced neurological impairment. DEX treatment reversed the effect of sevoflurane on both escape latency and time in original quadrant in a dose manner, and pretreatment with 75 µg/kg DEX had the most dramatic effect. DEX regulates the NR2B/ERK signaling in sevoflurane treated rats. Conclusion NR2B/ERK signaling is involved in sevoflurane induced neurological impairment. DEX may protect against sevoflurane induced neurological dysfunction in the developing rat brain via regulating the NR2B/ERK signaling.