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Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models.In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation.We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and particularly whether the control of TNT formation could influence the rescue function of stem cells.In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed.