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-alpha) 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-alpha 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-alpha induced effects. The results support TNF-alpha 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-alpha levels are elevated and inflammation/oxidative stress is suspected to be a contributing cause, such as Alzheimer's disease and Parkinson's disease.
Bjugstad
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Dept. of Psychology, University of South Florida, Tampa, FL 33620, USA.
Flitter
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Garland
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Arendash
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D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000975:Antioxidants; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha