Hypoxia-ischemia induces an endogenous reparative response by local neural progenitors in the postnatal mouse...

Perinatal hypoxia-ischemia in the preterm neonate commonly results in white matter injury for which there is no specific therapy. The subventricular zone (SVZ) of the brain harbors neural stem cells and more committed progenitors including oligodendroglial progenitor cells that might serve as replacement cells for treating white matter injury. Data from rodent models suggest limited replacement of mature oligodendroglia by endogenous cells. Rare newly born mature oligodendrocytes have been reported within the striatum, corpus callosum and infarcted cortex 1 month following hypoxia-ischemia. Whether these oligodendrocytes arise in situ or emigrate from the SVZ is unknown. We used a postnatal day 9 mouse model of hypoxia-ischemia, BrdU labeling of mitotic cells, immunofluorescence and time-lapse multiphoton microscopy to determine whether hypoxia-ischemia increases production of oligodendroglial progenitors within the SVZ with emigration toward injured areas. Although cells of the oligodendroglial lineage increased in the brain ipsilateral to hypoxic-ischemic injury, they did not originate from the SVZ but rather arose within the striatum and cortex. Furthermore, they resulted from proliferation within the striatum but not within the cortex. Thus, an endogenous regenerative oligodendroglial response to postnatal hypoxia-ischemia occurs locally, with minimal long-distance contribution by cells of the SVZ.