A substantial loss of transplanted neural stem cells is a major limitation to cell transplantation therapy of stroke. In this study, we provided in vitro evidence that doxycycline preconditioning of neural stem cells have resulted in decreased cell death and increased cell viability after oxygen-glucose deprivation-reoxygenation conditions that best mimics cerebral ischemia-reperfusion injury. Resistance to oxidative stress is one of the mechanisms of doxycycline-induced cytoprotection in neural stem cells as it significantly reduced the superoxide anion production. Moreover, doxycycline preconditioning also induced the expression of Nrf2 which is a basic transcription factor for a series of antioxidative and cytoprotective genes. Collectively, we suggested that doxycycline preconditioning of neural stem cells is a potential strategy to improve effectiveness of cell transplantation therapy. (C) 2013 Elsevier Inc. All rights reserved.