Experimental evidence to support the hypothesis that damage to vascular endothelium plays the primary role in the development of late radiation-induced CNS injury.

Experimental evidence has been obtained to support the view that late necrosis in the brain, after irradiation, is a consequence of damage to the vascular system. Rats were locally irradiated to the brain with a single dose of 25 Gy of X-rays and their response was compared with rats given the same treatment after administration of the radioprotector, Gammaphos. Time-dependent changes in endothelial cell number were determined for up to 65 weeks after irradiation. The complex pattern of changes in endothelial cell number, seen after irradiation alone, was not found in animals receiving Gammaphos prior to irradiation. The initial marked loss of endothelial cells, seen after 24 h in unprotected animals, was effectively prevented by the pre-administration of Gammaphos. The subsequent slow decline in endothelial cell density in Gammaphos treated animals was insufficient to induce an abortive attempt at endothelial cell re-population. This occurred between 26 and 52 weeks after irradiation in unprotected animals. By 65 weeks after irradiation <10% of animals receiving Gammaphos showed necrosis on histological evaluation. This compared with approximately 50% of the animals showing necrosis that had not received the radioprotector. Since the radioprotector is restricted to the vasculature of the brain these data indicate that endothelium is the primary target cell population, damage to which leads to the development of late radiation-induced necrosis in the brain.