Studies on DNA fragmentation and disruption of the blood-brain barrier in delayed radiation injuries in the rat brain

Delayed effect of radiation injury to the central nervous system often results in improper prognosis for the patients with malignant brain tumors, Two types of cell, the endothelial cell and the oligodendrocyte, are considered to be causative lesions for delayed radiation injury. Recently, morphological studies with both light and electron microscope have also indicated involvement of apoptosis at the acute stage of radiation injury, In the rat radiation injury model, we first examined the capillary endothelial cells when they were damaged after irradiation, using immunohistochemical analysis of endothelial blood antigen (EBA) as one of the indicators of normal function of the blood-brain barrier (BBB), Secondly, we examined the types and location of DNA-fragmented cells using in situ end-labeling using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling) method, A single dose of 10, 20 or 30 Gy was irradiated to the hemispheres and the brains were analyzed at 3, 6 and 12 months later, Although damage of endothelial cells was seen in the brains at 6 months after 20 Gy irradiation, disruption of BBB, as indicated by no immunoreactivity of EBA, occurred only in the brains at 12 months after 30 Gy irradiation, DNA fragmentation, indicated by TUNEL positive cells, were shown in the oligodendrocyte, astrocytes and endothelial cells in the brains at 6 months after 20 Gy irradiation, The results suggest that both disruption of BBB and apoptosis in the glial cells and endothelial cells are involved in the delayed radiation injury in the rat brain.