Abstract
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-α has been shown to be elevated in AIDS dementia complex brains and may contribute to AIDS dementia complex. To model elevated TNF-α in AIDS dementia complex, TNF-α was infused ICV bilaterally into rats for 3 days. TNF-α 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-α induced apoptosis. Both TNF-α and CPI-1189 treatment suppressed glial fibrillary acidic protein (GFAP) staining at the infusion site. TNF-α 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-α or CPI-1189 treatment was found on measures of oxidative stress. These results support TNF-α as a key agent for increasing apoptosis in AIDS dementia complex. Additionally, CPI-1189 treatment may protect against TNF-α induced apoptosis and astrogliosis in AIDS dementia complex. Lastly, the toxic effect of TNF-α and the protective effect of CPI-1189 may not be mediated primarily through manipulation of classic reactive oxygen species.