This suggested that OxS is a prerequisite for activation of Nrf2/ARE signaling by H2S. In addition, knockdown of astrocytic Nrf2 quelled the protective effect of H2S in NH4Cl-induced cytotoxicity and cell apoptosis, which indicated that the Nrf2/ARE signaling pathway mediates the neuroprotection of H2S against HE. The gene discussed is NFE2L2; the disease is hereditary elliptocytosis.