Update publication information. Hypoxic pre-conditioning has been demonstrated to increase the resistance of neural stem cells (NSCs) to hypoxic conditions, as well as to improve their capacity for differentiation and neuro-genesis. Extracellular vesicles (EVs) have recently emerged as critical mediators of cell-cell com-munication, but their role in this hypoxic conditioning is presently unknown. Here, we demon-strated that three hours of hypoxic pre-conditioning triggers significant neural stem cell EV release. Proteomic profiling of EVs from normal and hypoxic preconditioned neural stem cells identified 20 proteins that were up-regulated and 22 proteins that were down-regulated after hypoxic precon-ditioning. We also found an upregulation of some of these proteins by qPCR, thus indicating dif-ferences also at the transcript level within the EVs. Among the up-regulated proteins are CNP, Cyfip1, CASK, and TUBB5, which are well known to exhibit significant beneficial effects to neural stem cells. Thus, our results not only show a significant difference of protein cargo in EVs conse-quent to hypoxic exposure, but identify several candidate proteins that might play a pivotal role in the cell-to-cell mediated communication underlying neuronal differentiation, protection, matura-tion and survival following exposure to hypoxic conditions.