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J Neurosci. 2011 Jun 22;31(25):9205-21. doi: 10.1523/JNEUROSCI.0518-11.2011.

Cortical glial fibrillary acidic protein-positive cells generate neurons after perinatal hypoxic injury.

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Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.


Glial fibrillary acidic protein-positive (GFAP(+)) cells give rise to new neurons in the neurogenic niches; whether they are able to generate neurons in the cortical parenchyma is not known. Here, we use genetic fate mapping to examine the progeny of GFAP(+) cells after postnatal hypoxia, a model for the brain injury observed in premature children. After hypoxia, immature cortical astroglia underwent a shift toward neuronal fate and generated cortical excitatory neurons that appeared synaptically integrated into the circuitry. Fate-mapped cortical GFAP(+) cells derived ex vivo from hypoxic, but not normoxic, mice were able to form pluripotent, long-term self-renewing neurospheres. Similarly, exposure to low oxygen conditions in vitro induced stem-cell-like potential in immature cortical GFAP(+) cells. Our data support the conclusion that hypoxia promotes pluripotency in GFAP(+) cells in the cortical parenchyma. Such plasticity possibly explains the cognitive recovery found in some preterm children.

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