Our purpose was to noninvasively assess formation of the microvasculature, blood-brain barrier (BBB) and blood-CSF barrier formation of prenatal X-ray-induced CNS abnormalities using quantitative MRI. Eight pregnant female Sprague-Dawley rats were divided into two groups consisting of control and X-irradiated animals. After birth, 20 neonatal male rats were divided into four groups of five rats. To evaluate the development of the BBB, changes in T(1) induced by Gd-DTPA were compared quantitatively in normal and prenatally irradiated animals in the formative period 1 to 2 weeks after birth. To assess the abnormalities of the microvasculature, quantitative perfusion MRI and MR angiography were also used. Histology was also performed to evaluate the BBB (albumin) and vascular endothelial cells (laminin). Decreased cerebral blood flow (CBF) and angioarchitectonic abnormalities were observed in the prenatally irradiated rats. However, abnormalities of the BBB and blood-CSF barrier were not observed using Gd-enhanced MRI and albumin staining. Quantitative perfusion MRI, MR angiography and Gd-enhanced T(1) mapping are useful for assessing CNS disturbance after prenatal exposure to radiation. These techniques provide important diagnostic information for assessing the condition of patients during the early stages of life after accidental or unavoidable prenatal exposure to radiation.
The aim of this study was to spatio-temporally clarify gross structural changes in the forebrain of cynomolgus monkey fetuses using 7-tesla magnetic resonance imaging (MRI). T(1)-weighted coronal, horizontal, and sagittal MR slices of fixed left cerebral hemispheres were obtained from one male fetus at embryonic days (EDs) 70-150. The timetable for fetal sulcation by MRI was in good agreement with that by gross observations, with a lag time of 10-30 days. A difference in detectability of some sulci seemed to be associated with the length, depth, width, and location of the sulci. Furthermore, MRI clarified the embryonic days of the emergence of the callosal (ED 70) and circular (ED 90) sulci, which remained unpredictable under gross observations. Also made visible by the present MRI were subcortical structures of the forebrain such as the caudate nucleus, globus pallidus, putamen, major subdivisions of the thalamus, and hippocampal formation. Their adult-like features were formed by ED 100, corresponding to the onset of a signal enhancement in the gray matter, which reflects neuronal maturation. The results reveal a highly reproducible level of gross structural changes in the forebrain using a high spatial 7-tesla MRI. The present MRI study clarified some changes that are difficult to demonstrate nondestructively using only gross observations, for example, the development of cerebral sulci located on the deep portions of the cortex, as well as cortical and subcortical neuronal maturation.
We show that neuronal migration is disturbed by low-dose gamma-radiation of 0.24 Gy in the developing cerebral cortex of mice and suggest that neuronal progenitors in the S phase of mitosis are more sensitive than those in the G1/G0 phase. To pulse-label the fetal cells pregnant Slc:ICR mice were injected with bromodeoxyuridine (BrdU) at 10.00 pm on day 16 of pregnancy or at 9.30 am on day 17. The mice then were exposed to 0.24 Gy gamma- or sham-irradiation at 10.00 am on day 17 of pregnancy. At the time of exposure cells labeled on day 16 were regarded as having completed mitosis, and those labeled on day 17 as being in the S phase. Cell death in the fetal ventricular zone after exposure was negligible. Dams were allowed to give birth and rear their litters. Brain samples obtained from offspring on the 2nd day after birth and at 6 weeks of age were used for the immunohistochemical examination of BrdU-labeled cells. Labeled cells remaining in the ventricular zone were significantly more numerous in irradiated animals than in sham-exposed ones on the 2nd day after birth, in mice treated prenatally with BrdU on day 17 of pregnancy; whereas, mice treated with BrdU on day 16 showed no statistically significant difference. At 6 weeks of age, in both groups most of the labeled cells were present in layers II-III of the SmI cerebral cortex. But, in the irradiated animals the labeled cells in these layers were significantly fewer and those in layers IV-VI more numerous than in the sham-exposed mice in both group treated with BrdU on day 16 or 17.
Embryos are more susceptible to ionizing radiation than adults. Heterotopic gray matter was found in the brain of victims prenatally exposed to the atomic bomb. We reproduced this malformation in mice. Many cells in the ventricular zone, except for radial glial fibers, were destroyed by radiation. Following the proliferation of surviving cells, postmitotic neurons migrated to the cortical plate. Some neurons in areas missing radial fibers could not migrate and remained as heterotopic gray matter. On the other hand, there is no evidence of human congenital abnormalities caused by nonionizing radiation. Teratogenicity of microwaves in experimental animals is regarded as their thermal effect. However, some studies have reported effects of radio frequency and extremely low-frequency electromagnetic fields on cell proliferation and differentiation.
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