Preventive actions of a synthetic antioxidant in a novel animal model of AIDS dementia

Accumulating evidence indicates that the mechanism for causing AIDS dementia complex (ADC) involves the release of damaging inflammatory-related agents by HIV-infected microglia in the brain resulting in CNS oxidative damage. One such agent, tumor necrosis factor alpha (TNF-α) is consistently elevated in the brains of ADC patients compared to non-demented HIV patients. To model this aspect of ADC in rats, chronic ventricular infusions of TNF-α were given and found to induce several 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-α induced effects. The results support TNF-α as a key toxic agent in ADC and provide the first in vivo evidence that chronic treatment with a synthetic antioxidant may protect HIV-infected patients against ADC. Our findings may also have implications in other neurological diseases where brain TNF-α levels are elevated and inflammation/oxidative stress is suspected to be a contributing cause, such as Alzheimer's disease and Parkinson's disease.