| Transient hypoxia induces cell death in area CA1 of the rat hippocampus, but spares cells in CA2/3. Activation of stem cells in the subgranular zone of the dentate gyrus, and their subsequent proliferation and migration into damaged regions of the brain may serve in the adult to replace lost neurons. A critical question is if these new neurons form appropriate connections and restore function. In rat organotypic hippocampal cultures cell death, maturation and migration of neural stem cells (NSCs) and neuronal progenitor cells (NPCs) were confirmed after exposure to transient hypoxia (6 hours) and reoxygenation. NSCs, NPCs, immature neurons, and more mature neurons were immunohistochemically detected with antinestin, doublecortin, Tuj-1, and NeuN, respectively, and cell proliferation with antiPCNA immunostain, and BrdU uptake. Using electrophysiological techniques, in hypoxic cultures synaptic signals were absent in CA1 24h after hypoxia, but returned by 72h. These studies suggest hippocampal brain cultures are are sensitive to hypoxia, and respond with restoration of physiologic function by new neurons. |
