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In addition, HA treatment decreased sevoflurane-induced neuronal apoptosis in the hippocampus and alleviated Aβ accumulation. Our results also show that the neuroprotective effect of HA is associated with the activation of Nrf2 signaling. Human neuroblastoma H4 cells were used as a model to examine the protective activity of HA against sevoflurane-induced neurotoxicity. In addition, our results show that the inhibition of Nrf2 by a specific inhibitor or targeting siRNA significantly compromises the attenuating effect of HA on sevoflura