Time- and dose-related changes in the white matter of the rat brain after single doses of X rays

Abstract

Following the local irradiation of the rat brain with single doses of 17.5-25 Gy of X rays, necrosis of the white matter was seen after a latent interval of greater than 26 weeks. At 39 weeks and 52 weeks after irradiation the incidence of necrosis was dose-related. The doses associated with a 50% incidence of necrosis in the white matter (ED50) at these times were 23.45 +/- 0.49 and 20.98 +/- 0.91 Gy, respectively. At both these times the incidence of necrosis was higher in the fimbria than in the capsula interna and the corpus callosum. This reflects a variation in the latency time for the appearance of necrosis. Necrosis occurs earlier in the fimbria. In the corpus callosum and the capsula interna the latency times for the appearance of necrosis were also dose-dependent. In the latent period prior to the onset of necrosis of the fimbria, a number of dose-related changes were seen in the vasculature and the associated astroglial cells. These changes, which included blood vessel dilation, blood vessel wall thickening, endothelial cell nuclear enlargement and the hypertrophy of perivascular astrocytes, were highly correlated and when combined appeared to represent a "unit of tissue injury". The incidence and severity of this "unit of tissue injury" apparently increased with time after irradiation until necrosis ensued. These dose-related vascular/glial changes were preceded by a reduction in the endothelial cell and vascular density. No early changes were seen in the number of glial parenchymal cells.