Hydrocephalus in mice following X-irradiation at early gestational stage: possibly due to persistent deceleration of cell proliferation.
The pathogenesis of X-ray-induced congenital hydrocephalus was studied. Pregnant mice were irradiated at 1.4 Gy on gestational day 7 (G7). Four hours after irradiation, extensive cell death was evident in the neuroepithelium and underlying mesoderm of the head region, and proliferating cell nuclear antigen (PCNA)-immunoreactive cells almost disappeared. Embryos with thinner lamina terminalis of the telencephalon, when compared with that of the control, were found in the irradiated group on G9. As early as G11 in some irradiated embryos the telencephalic wall was thinner and lateral ventricles were larger than those of the control. The choroid invagination from the lamina terminalis began on G11 in the control brain, but not in the affected brain. During the following development, fetuses with readily apparent hydrocephalus were consistently found among irradiated fetuses. In these brains the brain mantle was thinner, the corpus striatum and thalamic regions were smaller, and lateral ventricles were larger than those of the control. Even on G11 and G13 the frequencies of PCNA-positive cells in the brain mantle and other brain regions were lower in the hydrocephalic brain than those of the control, suggesting a decelerated proliferation of successive cell generations following exposure to X-rays. The cerebral aqueduct was open in the hydrocephalic brain during the fetal period when the lateral ventricles were dilated. The head was vaulted after birth but the cerebral aqueduct was not completely occluded even in these animals. These findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus.
Aolad
H M
HM
Department of Teratology and Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
Inouye
M
M
Darmanto
W
W
Hayasaka
S
S
Murata
Y
Y
D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D005314:Embryonic and Fetal Development / Q000528:radiation effects*; D005260:Female; D006849:Hydrocephalus / Q000209:etiology* / Q000473:pathology; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014965:X-Rays