PREVENTIVE ACTIONS OF A SYNTHETIC ANTIOXIDANT IN A NOVEL ANIMAL-MODELOF AIDS DEMENTIA

Accumulating evidence indicates that the mechanism for causing AIDS de mentia complex (ADC) involves the release of damaging inflammatory-rel ate agents by HIV-infected microglia in the brain resulting in CNS oxi dative damage. One such agent, tumor necrosis factor alpha (TNF-alpha) is consistently elevated in the brains of ADC patients compared to no n-demented HIV patients. To model this aspect of ADC in rats, chronic ventricular infusions of TNF-alpha were given and found to induce seve ral aspects of ADC, including weight loss, learning/memory impairment, enlarged lateral ventricles, and increased apoptosis. Concurrent oral treatment with the antioxidant CPI-1189 prevented all of these TNF-al pha induced effects. The results support TNF-alpha as a key toxic agen t in ADC and provide the first in vivo evidence that chronic treatment with a synthetic antioxidant may protect HN-infected patients against ADC. Our findings may also have implications in other neurological di seases where brain TNF-alpha levels are elevated and inflammation/oxid ative stress is suspected to be a contributing cause, such as Alzheime r's disease and Parkinson's disease. (C) 1998 Elsevier Science B.V. Al l rights reserved.