Postnatal development of the rat CNS following in utero exposure to a low dose of ionizing radiation.

Summary In utero exposure to ionizing radiation is of importance because of its potential health risks. The developing nervous system is particularly vulnerable and the consequences of exposure to low levels of radiation (≤ 1 Gy) are not well established. The developmental effects of maternal exposure to 50 cGy gamma-radiation on gestational days (GD) 9.5, 15, and 18 were investigated in Sprague Dawley rats. Rats exposed on GD-9.5 along with approriate controls were killed at 4 h, 48 h, and 10 days post-irradiation while those irradiated on GD-15 and GD-18 were killed postnatally (PN) on days 7 and 26. All were examined for developmental anomalies and representative samples of brains were processed for microscopic study. No significant developmental differences were observed between irradiated and control embryos killed 48 h after irradiation on GD 9.5. However, in irradiated fetuses a larger number of developmental anomalies were observed at term. Defects of the eye and of spinal curvature were the most common malformations encountered. Mitoses were reduced within the neuroepithelium of embryos irradiated on GD-9.5 and evidence of pyknosis and necrosis was seen 4 h after irradiation. The capacity of surviving primitive neural cells for repair, however, was such that by 48 h after exposure the irradiated nervous system no longer differed from controls. Rats irradiated on GD-15 and GD-18 and examined on PN-26 exhibited clusters of small, dark, pyknotic neurons within the hippocampal and dentate gyri, often bilaterally. They were found with an incidence of 57 % and 33 % in rats irradiated on G-15 and G-18, respectively. Significant cerebellar lesions were also seen in 14% and 22% of rats irradiated on GD-15 and GD-18 respectively, and killed on PN-26. In these rats the granular cell layer of the cortex harbored numerous lucent islands containing reduced numbers of granule cells. The vulnerability of the hippocampal neurons can be explained by their morphogenesis being coincident with the period of irradiation. However, since cerebellar microneurons are largely acquired postnatally, radiation in this case likely affected the precursors, proliferative and/or migratory cells of the external granular layer. Alternatively, it may have affected the normal differentiation of Purkinje cells which in turn removed or altered some guiding influence they provide on the normal development of internal granule cells.