Structure and pathogenesis of cortical nodules induced by prenatal X-irradiation in the rat

Segmentation of the cerebral cortex with formation of nodules, predominating in the upper cortical levels, was found in the rat after 200 cGy X-ray exposure at embryonic days 15, 17 or 19. Nodules were composed of pyramidal and nonpyramidal neurons occupying normal positions at different levels of the cerebral cortex as revealed with parvalbumin and calbindin D-28k immunocytochemistry. The nodules, which were large in animals irradiated at embryonic day 15 but reduced to groups of a few cells in rats irradiated at embryonic day 19, were separated by low cell density zones. Autoradiographic studies using tritiated methylthymidine injections given to pregnant irradiated rats at different days of gestation further demonstrated a preserved inside-out gradient of cortical neurogenesis in this cortical malformation. Morphological studies of irradiated embryos disclosed that groups of dead cells were separated by patches of preserved cells in the germinal layer 6 h after irradiation. Columns of migrating neuroblasts separated by low cell density zones were seen 24 h later. These features suggest that cortical nodules observed after prenatal X-irradiation were the result of multifocal cell death in vulnerable (at the moment of X-ray exposure) proliferative units of the germinal neuroepithelium, combined with normal neurogenesis and migration of neuroblasts from the preserved germinal zones. These findings also suggest that cell proliferation is not uniform through the germinal layer but occurs synchronously in alternate proliferative units. These proliferative units probably co-generate pyramidal and nonpyramidal cells.