Experimental Selective Alteration of Blood-Brain Barrier by X-Irradiation

OST lesions of the central nervous system are associated with an altered blood-brain barrier. Thus isotopic brain scanning has become an important diagnostic tool, and chemotherapy of brain tumors remains potentially useful if differential selective uptake of a chemotherapeutic agent by the tumor can be improved. However, the breakdown of the blood-brain barrier (BBB) is often not sufficient clearly to delineate the lesion nor selectively to absorb a metabolic antagonist. An increased differential between BBB of the lesion and normal tissue is desirable for diagnosis and treatment. Shealy and Crafts 15 demonstrated the possibility of selectively altering BBB. They produced symmetrical bilateral ultrasonic lesions in cat cerebral cortex, and 4 to 6 days later the right carotid artery was injected with 50% Hypaque, 15% ethanol, or distilled water. A dosage of each of these substances was found which increased the uptake of trypan blue and Mercury-203 (Neohydrin) in the injected lesion when compared to the control lesion, but which would not increase the uptake of these substances by normal brain. The differential uptake in the injected lesion was 7 to 10 times that in either normal brain or the control lesion on the opposite side. This method of selectively altering the BBB had an obvious disadvantage in that it required intra-arterial injection of the damaging agent. It seemed worthwhile, therefore, to try to find another method for accomplishing the same effect. The effect of x-irradiation on the brain has been studied extensively? ,9 It is clear that x-ray will, in appropriate dosages, alter the permeability of the BBB, as evidenced by