Exposure to in utero irradiation produces disruption of radial glia in rats

In utero exposure of fetal rats to gamma-irradiation produces diffuse cortical dysplasia and neuronal heterotopia. This study examined the effects of in utero irradiation on radial glia and astrocytes in the perinatal period in order to better understand the specific mechanisms which produce cortical dysgenesis in this model. Fetal rats were exposed to 225 cGy of gamma-irradiation on embryonic day 17. Vibratome sections were processed for cresyl violet staining and immunohistochemistry with Rat-401 and an antibody for glial fibrillary acidic protein (GFAP) on E20, P0, P2, and P4. In utero irradiation produced a profound disruption of the radial glia which lasted throughout the perinatal period. This injury coincided with the location of the most severe cortical dysplasia in this model. In addition, there was increased GFAP immunoreactivity in the cortex and the striatum when compared to nonirradiated controls on P0, P2, and P4. Our results demonstrate that in utero irradiation has a lasting, injurious effect on radial glia and also incites a reactive astrocytic response. This suggests that disruption of radial glial fibers by gamma-irradiation is a major factor in the pathogenesis of cortical dysgenesis in this model.