Modeling the neurovascular niche: murine strain differences mimic the range of responses to chronic hypoxia in the premature newborn.

Preterm birth results in significant cognitive and motor disabilities, but recent evidence suggests that there is variable recovery over time. One possibility that may explain this variable recovery entails variable neurogenic responses in the subventricular zone (SVZ) following the period of chronic hypoxia experienced by these neonates. In this report, we have characterized the responses to chronic hypoxia of two mouse strains that represent a wide range of susceptibility to chronic hypoxia. We determined that C57BL/6 pups and neural progenitor cells (NPCs) derived from them exhibit a blunted response to hypoxic insult compared with CD-1 pups and NPCs. Specifically, C57BL/6 pups and NPCs exhibited blunted in vivo and in vitro proliferative and increased apoptotic responses to hypoxic insult. Additionally, C57BL/6 NPCs exhibited lower baseline levels and hypoxia-induced levels of selected transcription factors, growth factors, and receptors (including HIF-1alpha, PHD2, BDNF, VEGF, SDF-1, TrkB, Nrp-1, CXCR4, and NO) that determine, in part, the responsiveness to chronic hypoxic insult compared with CD-1 pups and NPCs, providing insight into this important and timely problem in perinatology.