Delayed effects of prenatal low-dose irradiation in the white matter of the rat brain.

PURPOSE: This study is part of a general search for the anatomical bases of the severe mental retardation syndrome caused by prenatal irradiation. More specifically, it seeks reasons for the high radiosensitivity of a white matter area, the cingulum of the corpus callosum. MATERIALS AND METHODS: Pregnant primiparous Wistar rats were exposed to X-rays at 12, 13, 14 or 15 days of gestation (E12, E13, E14 or E15) with single low doses of 180 mGy. A high dose of 500 mGy was given at E15 for a complementary study. The brains of the female offspring were collected at 1 and 3 months of age. The affinity of osmium tetroxide for the white matter was used to recognize and quantify cingulum areas in a series of coronal sections made at different positions along the antero-posterior axis of the brains. RESULTS: A 180 mGy dose of X-rays caused an atrophy of the cingulum; the effect was particularly significant in the 1-month-old brains after an exposure at E13 or at E14, and increased in the 3-month-old animals exposed at E15. The axonal size distribution was unchanged in the 3-month-old cingulums treated with 500 mGy at E15. CONCLUSIONS: The atrophy of the cingulum is due to a loss of axons, which are abundant in this area. As a consequence of axon loss, a reduction of the postnatal myelination enhances the volumetric decrease of the cingulum at 3 months of age.

Brain atrophy after foetal exposure to very low doses of ionizing radiation.

Acute, high dose-rate, exposure of the rat embryo on day 15 post-conception (PC) causes a reduction of brain weight in adult life that is proportional to the dose received. Doses as low as 10 mGy of 600 keV neutrons, from a Van de Graaff accelerator, or 100 mGy of 250 kV X-rays are capable of eliciting a significant effect. The relative biological effectiveness for acute neutron exposure compared with 250 kV X-rays was 3.5. A brain weight reduction was also observed after gamma-ray exposures protracted over 4 or 6 days, during cerebral corticogenesis. The dose-rate reduction factor was only 1.5 for exposure from days 12 to 16 PC and 3.3 for exposure from days 14 to 20 PC. In relation with the decrease in brain weight, the cingulum bundle, a myelinated structure associated with the corpus callosum, displayed a significant reduction in size. The implications of these observations for human exposures are discussed.

Naturally occurring, postnatal cell death in the cerebral cortex of the micrencephalic rat induced by prenatal X-irradiation.

Naturally occurring postnatal cell death in the somatosensory cortex and medial cortical areas was examined in micrencephalic rats produced after exposure to 100 cGy X-rays at embryonic day 15. The absolute numbers of dead cells per tissue section were not affected in the future subcortical white matter, but were severely decreased in the cerebral cortex when compared with age-matched controls. Furthermore, the proportion of cortical dead cells per 1000 live neurons in the cerebral cortex and the cumulative cell death across time were significantly reduced in irradiated animals. These results suggest that naturally occurring postnatal cell death in the cerebral cortex is reduced in micrencephaly.

Development of dendritic spines in the cerebral cortex of the micrencephalic rat following prenatal X-irradiation.

Postnatal development of dendritic spines (DS) on the 500-microns-proximal region of the apical dendrite of large layer V pyramidal neurons of the somatosensory cortex (Par 1) was studied with the rapid Golgi method in micrencephalic rats produced after exposure to 100 cGy X-irradiation at embryonic day 18. Treated rats examined at the age of 15 days had more DS than age-matched controls, whereas the reverse occurred in rats aged 30 days. After this time the number of DS decreased in normal rats. As a result, irradiated and control rats aged 90 days had about the same number of DS in the proximal region of the apical dendrite. These results suggest that development of DS appears early, and that natural overproduction and elimination of DS is impaired in the cerebral cortex of micrencephalic rats.

Influence of manganese on the gastrointestinal absorption of cadmium in rats.

Four groups of male rats were given the following oral treatment: control group (n = 20) deionized drinking water, Mn group (n = 20) deionized drinking water containing 56 ppm Mn2+ (1 mmol/l), Cd group (n = 10) deionized drinking water containing 112 ppm Cd2+ (1 mmol/l) and Cd + Mn group (n = 10) deionized drinking water containing 112 ppm Cd2+ and 56 ppm Mn2+. Half of each group was sacrificed after 4 weeks and the other half after 8 weeks of treatment. At each time interval, the mean levels of Mn in blood, in urine and in the various tissues did not differ between the control and Mn groups. Furthermore, comparable Mn levels were found after 4 and 8 weeks of treatment. Microscopical examination of the brain failed to reveal any overt morphological alteration in the Mn group. With respect to the control group, the Cd and Cd + Mn groups exhibited increased levels of Cd in blood, urine, liver, whole kidney, kidney cortex and in brain (cortex, cerebellum, basal ganglia), but the Cd + Mn groups showed invariably lower levels than the Cd group after 4 weeks as well as after 8 weeks. These results suggest that the rate of gastrointestinal absorption of Cd is decreased by supplementation of the drinking water with a 'non-toxic' dose of Mn2+.

A glial progenitor cell in the cerebral cortex of the adult rat.

A glial cell subtype, previously classified as a beta astrocyte on the basis of its ultrastructural and radiobiological characteristics, has now been shown to represent the most mitotically active component of the glial population in the grey matter of the cerebral cortex of the young adult rat. The labelling index of 0.83% was evaluated using semithin sections. A role for beta astrocytes as macroglial precursors is supported by the present observations. However, the mechanisms responsible for the intermediate radiosensitivity of these elements remain uncertain.

[Prenatal irradiation of the rat with very weak doses of X-rays: lesions of the white matter]. / Irradiation prénatale du rat à très faible dose de rayons X: lésions de la substance blanche.

The depth of the cingulum bundle, a myelinated substructure of the corpus callosum was found to represent a sensitive indicator of exposure to X-irradiation in utero at dose levels as low as 20 cGy. In such conditions, the origin of the anatomical damage is probably to be found in a disordered sequence of morphogenetic events rather than in mitotic cell death processes.

Effects of heavy metals (Cd, Tl, Zn and Pb) on glial cells.

This communication deals with an ultrastructural assay of certain quantitative brain parameters susceptible to be modified during heavy metal intoxication. It particularly focusses on the changes in the populations of glial cells which appear as a most sensitive morphological indicator of brain poisoning.