Vascular cells provide a neural stem/progenitor cell (NSPC) niche that regulates expansion and differentiation of NSPCs within the germinal zones of the embryonic and adult brain under both physiologic and pathologic conditions. Here, we examined the NSPC-endothelial cell (NSPC/EC) interaction under conditions of
ischemia, both in vitro and after intracerebral
transplantation. In culture, embryonic mouse NSPCs supported capillary morphogenesis and protected ECs from cell death induced by serum
starvation or by transient
oxygen and
glucose deprivation (OGD). Neural stem/progenitor cells constitutively expressed
hypoxia-inducible factor 1alpha (HIF-1alpha)
transcription factor and
vascular endothelial growth factor (
VEGF), both of which were increased approximately twofold after the exposure of NSPCs to OGD. The protective effects of NSPCs on ECs under conditions of serum
starvation and
hypoxia were blocked by pharmacological inhibitors of
VEGF signaling,
SU1498 and Flt-1-Fc. After intracerebral
transplantation, NSPCs continued to express HIF-1alpha and
VEGF, and promoted microvascular density after focal
ischemia. These studies support a role for NSPCs in stabilization of vasculature during
ischemia, mediated via HIF-1alpha-VEGF signaling pathways, and suggest therapeutic application of NSPCs to promote revascularization and repair after
brain injury.