CPI-1189 prevents apoptosis and reduces glial fibrillary acidic protein immunostaining in a TNF-alpha infusion model for AIDS dementia complex

AIDS dementia complex (ADC) is characterized by increased apoptosis, gliosi s, and oxidative stress in the CNS, as well as a compromised blood-brain ba rrier. TNF-alpha has been shown to be elevated in AIDS dementia complex bra ins and may contribute to AIDS dementia complex. To model elevated TNF-alph a in AIDS dementia complex, TNF-alpha was infused ICV bilaterally into rats for 3 days. TNF-alpha treatment increased apoptosis around the infusion si te and selectively in the septum and corpus callosum, Co-administration of the synthetic antioxidant CPI-1189 prevented TNF-alpha induced apoptosis. B oth TNF-alpha and CPI-1189 treatment suppressed glial fibrillary acidic pro tein (GFAP) staining at the infusion site. TNF-x did not significantly affe ct the integrity of the blood-brain barrier, but CPI-1189 treatment increas ed blood-brain barrier integrity at the infusion site. No effect of TNF-alp ha or CPI-1189 treatment was found on measures of oxidative stress. These r esults support TNF-alpha as a key agent for increasing apoptosis in AIDS de mentia complex. Additionally, CPI-1189 treatment may protect against TNF-al pha induced apoptosis and astrogliosis in AIDS dementia complex. Lastly, th e toxic effect of TNF-alpha and the protective effect of CPI-1189 may not b e mediated primarily through manipulation of classic reactive oxygen specie s.