Missing description had to be pieced together by reviewer. This is the second time that no abstract was provided; the application should have been considered incomplete). The long-term objective is to identify mechanisms that are critical for regeneration and repair following hypoxia. Chronic sublethal hypoxia (CSH) in neonates may induce a regenerative response that is attempting to replace cells lost through hypoxia-induced decreased proliferation and increased apoptosis. Several gene products involved in brain growth and cell proliferation during embryogenesis are re-activated under hypoxic conditions, including basic Fgf (Fgf2), Fgf receptor-1 (Fgfgr-1), and Fgf target genes. Because Fgf2 and Fgfr-1 are also necessary for neural stem cell/progenitor cell proliferation in the postnatal subventricular zone (SVZ), this pathway is hypothesized as being critical for an effective post-hypoxic regenerative response. This project will measure proliferation and apoptosis, as well as expression of Fgfr- 1 and other growth factor receptors during and after hypoxia in the SVZ and the hippocampal subgranular layer (HSL). Two mouse strains differing in their sensitivity to hypoxia will be used. Fgf2 knockout mice, as well as mice with a conditional Fgfr-1 deletion will be studied. The experiments are expected to determine whether Fgfr-1 signaling is critical for cell genesis and /or cell survival after hypoxia.
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