Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) induces severe injury to neuronal cells. The expression and potential function of NKILA (NF-kappa B Interacting LncRNA) in OGDR-treated neuronal cells were tested in this study. We show that OGDR induced NKILA upregulation to in-activate NF-kappa B signaling in SH-SY5Y cells and primary murine hippocampal neurons. Conversely, shRNA-mediated NKILA silencing almost reversed OGDR-induced NF-kappa B inhibition. OGDR-induced neuronal cell viability reduction, apoptosis and necrosis were largely attenuated by NKILA shRNA as well. Conversely, ectopic overexpression of NKILA by a lentiviral vector enhanced OGDR-induced SH-SY5Y cell death. For the mechanism study, we show that OGDR downregulated miR-103 and miR-107 to induce NKILA upregulation in neuronal cells. Transfection of miR-103 mimic or miR-107 mimic almost reversed OGDR-induced NKILA upregulation, NF-kappa B in-activation and SH-SY5Y cell death. Taken together, OGDR induces NKILA upregulation to in-activate NF-kappa B signaling, which mediates subsequent neuronal cell death. NKILA could be a novel therapeutic target of ischemic neuronal injury. (C) 2018 Elsevier Inc. All rights reserved.