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

Abstract

Dexmedetomidine (DEX) is a potent α‑2 adrenergic receptor agonist and has been widely applied in clinic. The present study explored the protective effect of DEX on sevoflurane‑induced learning and cognitive impairment and examined its underlying mechanism. Sprague‑Dawley rat pups were exposed to 0.85% sevoflurane for 6 h and injected with DEX in different doses. The Morris water maze test was performed to evaluate the learning and memory function of rats. Western blot was used for the measurement of protein levels. The water maze results indicated that sevoflurane treatment increased the escape latency but reduced the time spent in the 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 DEX had the most dramatic effect. DEX regulated the NR2B/ERK signaling in sevoflurane treated rats. 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.