RT Journal Article SR Electronic T1 Fgfr1 Is Required for Cortical Regeneration and Repair after Perinatal Hypoxia JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 1202 OP 1211 DO 10.1523/JNEUROSCI.4516-08.2009 VO 29 IS 4 A1 Devon M. Fagel A1 Yosif Ganat A1 Elise Cheng A1 John Silbereis A1 Yasushi Ohkubo A1 Laura R. Ment A1 Flora M. Vaccarino YR 2009 UL http://www.jneurosci.org/content/29/4/1202.abstract AB Chronic postnatal hypoxia causes an apparent loss of cortical neurons that is reversed during recovery (Fagel et al., 2006). The cellular and molecular mechanisms underlying this plasticity are not understood. Here, we show that chronic hypoxia from postnatal days 3 (P3) to 10 causes a 30% decrease in cortical neurons and a 24% decrease in cortical volume. T-brain-1 (Tbr1)+ and SMI-32+ excitatory neuron numbers were completely recovered 1 month after the insult, but the mice showed a residual deficit in Parvalbumin+ and Calretinin+ GABAergic interneurons. In contrast, hypoxic mice carrying a disrupted fibroblast growth factor receptor-1 (Fgfr1) gene in GFAP+ cells [Fgfr1 conditional knock-out (cKO)], demonstrated a persistent loss of excitatory cortical neurons and a worsening of the interneuron defect. Labeling proliferating progenitors at P17 revealed increased generation of cortical NeuN+ and Tbr1+ excitatory neurons in wild-type mice subjected to hypoxic insult, whereas Fgfr1 cKO failed to mount a cortical neurogenetic response. Hypoxic wild-type mice also demonstrated a twofold increase in cell proliferation in the subventricular zone (SVZ) at P17 and a threefold increase in neurogenesis in the olfactory bulb (OB) at P48, compared with normoxic mice. In contrast, Fgfr1 cKO mice had decreased SVZ cell proliferation and curtailed reactive neurogenesis in the OB. Thus, the activation of FGFR-1 in GFAP+ cells is required for neuronal recovery after neonatal hypoxic injury, which is attributable in part to enhanced cortical and OB neurogenesis. In contrast, there is incomplete recovery of inhibitory neurons after injury, which may account for persistent behavioral deficits.