Delayed vascular injury after single high-dose irradiation in the rat brain: histologic immunohistochemical, and angiographic studies.

Abstract

To investigate structural and functional changes in rats after focal brain irradiation by using histologic, immunohistochemical, and angiographic methods. Sixty rats were irradiated stereotactically with photons from a 15-MeV linear accelerator. Two collimators and single doses ranging from 20 to 100 Gy were used to treat stereotactically defined areas of 3.7- and 4.7-mm cross section (80% isodose) in the right frontal lobe. The dose-response relationship for the end-point necrosis at 19 months revealed a mean tolerance dose (D50) of 34.2 Gy (standard errors: +4.1, -3.7 Gy). Histologic, immunohistochemical, and angiographic examinations were performed to evaluate delayed radiation effects. All animals irradiated with 100 Gy developed radiation necrosis after 9 months. Microangiography and immunohistochemical fluorescence staining of the endothelial cells revealed dose-dependent vascular dilatation and rarefaction. Animals irradiated with 20-50 Gy showed no morphologic changes after 9 months. With irradiation of 30-50 Gy, histologic vascular changes that increased with dose were found after 19 months. At that time, no changes were detected after irradiation with 20 Gy with both field sizes and after irradiation with 30 Gy and the 2-mm collimator. Radiation-induced functional disturbances of the brain vasculature could be demonstrated by extravasation of contrast medium by using a microangiographic technique. The observed effect had a definite dependence on dose, volume, and time after treatment.