Localization of goldthioglucose and bipiperidyl mustard lesions near artificial disruptions of the blood-brain barrier.

Administration of goldthioglucose (GTG) or bipiperidyl mustard (BPM) causes obesity and lesions in hypothalamus, medulla, and other regions of the brain. Each of these lesions is adjacent to one of the specialized circumventricular areas that differ from the remainder of the brain in their natural lack of a blood-brain barrier. In the present work, the blood-brain barrier was artificially disrupted by a large thermal injury of the cerebral cortex. In rats and mice prepared in this manner, both chemicals induced lesions in the viable brain tissue adjacent to the thermal injury. This provides strong support for the role of the blood-brain barrier in the localization of GTG and BPM lesions in hypothalamus and medulla. Localization of lesions near thermal injuries was much less with GTG than with BPM. This suggests that factors other than blood-brain barrier are also involved in the localization of GTG lesions. These findings not only help to elucidate the pathogenesis of the hypothalamic lesions, but they also open a new approach to work on the role of receptors, vasoactive substances, and other intermediaries in the mechanism of GTG damage.