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

Abstract

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. Fatemapped cortical GFAP+ cells derived ex vivo from hypoxic, but not normoxic, mice were able to form pluripotent, long-term selfrenewing 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. © 2011 the authors.