salicylates and AIDS-Dementia-Complex

AIDS dementia complex (ADC) is characterized by increased apoptosis, gliosis, and oxidative stress in the CNS, as well as a compromised blood-brain barrier. TNF-alpha has been shown to be elevated in AIDS dementia complex brains and may contribute to AIDS dementia complex. To model elevated TNF-alpha in AIDS dementia complex, TNF-alpha was infused ICV bilaterally into rats for 3 days. TNF-alpha treatment increased apoptosis around the infusion site and selectively in the septum and corpus callosum. Co-administration of the synthetic antioxidant CPI-1189 prevented TNF-alpha induced apoptosis. Both TNF-alpha and CPI-1189 treatment suppressed glial fibrillary acidic protein (GFAP) staining at the infusion site. TNF-alpha did not significantly affect the integrity of the blood-brain barrier, but CPI-1189 treatment increased blood-brain barrier integrity at the infusion site. No effect of TNF-alpha or CPI-1189 treatment was found on measures of oxidative stress. These results support TNF-alpha as a key agent for increasing apoptosis in AIDS dementia complex. Additionally, CPI-1189 treatment may protect against TNF-alpha induced apoptosis and astrogliosis in AIDS dementia complex. Lastly, the toxic effect of TNF-alpha and the protective effect of CPI-1189 may not be mediated primarily through manipulation of classic reactive oxygen species.

Topics: Administration, Oral; AIDS Dementia Complex; Animals; Antioxidants; Apoptosis; Astrocytes; Basal Ganglia; Blood-Brain Barrier; Butanes; Corpus Callosum; Depression, Chemical; Disease Models, Animal; Drug Evaluation, Preclinical; Glial Fibrillary Acidic Protein; Gliosis; Hydroxyl Radical; Immunoglobulin G; Injections, Intraventricular; Lipid Peroxidation; Male; Neocortex; Neuroprotective Agents; Nitrogen Oxides; Oxidative Stress; Rats; Rats, Sprague-Dawley; Salicylates; Septum Pellucidum; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha