Therefore, the objectives of this study were to: i) assess the potential role of Nrf2 signaling in hypoglycemia-induced endothelial dysfunction and BBB permeability and, ii) address the molecular mechanisms underlying Nrf2 down-regulation by hypoglycemia in brain microvascular endothelial cells using hCMEC/D3 cell line [30]. The gene discussed is NFE2L2; the disease is endothelial dysfunction.