NFkappaB activation, TNF-alpha expression, and apoptosis in the AIDS-Dementia-Complex.

The role of NFkappaB activation and its relationship to inflammatory mediators and apoptosis in the HIV-infected brain have remained uncertain. The cellular and regional distribution of NFkappaB, TNF-alpha, and apoptosis was examined in the frontal cortex (FC), deep white matter (DWM) and the basal ganglia (BG) of 17 patients with ADC. Nuclear staining for NFkappaB was localized predominantly to perivascular microglia/macrophages in the BG and DWM and correlated with ADC severity. Correlations were further found with HLA-DR, iNOS, TNF-alpha, and gp41 expression in these regions. The number of TUNEL-positive cells, particularly in the BG, correlated with ADC stage. Logistic regression analysis further showed a significant relationship between the likelihood of TUNEL staining in the BG and worsening cognitive impairment.