Gap-junctional intercellular communication between grafted neural stem cells (NSCs) and host cells seems to be essential for many of the functional and beneficial interactions after NSC engraftment. Gap-junctional communication is also known to increase in the central nervous system after hypoxia and ischemia. We therefore hypothesized that controlled hypoxic preconditioning of murine NSCs (C17.2) before the engraftment is a reliable method to increase connexin 43 expression and improve subsequent graft and host communication. Data indicated that 3-h exposure to hypoxia increased the number of connexin 43 aggregates in treated NSCs by 31%. This was paralleled by enhanced hemichannel function showed by faster calcein dye efflux and an augmentation of the early functional graft and host communication.