Neuropathol Appl Neurobiol. 1995 Dec;21(6):518-28. Unique Identifier :
Human immunodeficiency virus type 1 (HIV-1) infection of the central
nervous system is associated with decreased neuronal density in discrete
areas of the brain. Neuronal loss may occur via apoptosis, initiated by
soluble neurotoxic factors secreted from HIV-1 infected macrophages and
microglia. To examine further the molecular events involved in HIV-1
neuropathogenesis, we assessed the activity of NF kappa B, an inducible
transcription factor involved in the activation of multiple
proinflammatory, and potentially neurotoxic, genes. NF kappa B was
analysed by immunocytochemistry using specific antisera to the NF kappa
B p. 50 and p. 65 subunits. Brains from children with HIV-1 encephalitis
and progressive encephalopathy were found to contain increased numbers
of NF kappa B immunoreactive cells, relative to control brains (HIV-1
negative, or HIV-1 positive without encephalitis). Double-labelling
studies using antibodies to CD68, or RCA-1 lectin, markers for cells of
monocyte/macrophage lineage, revealed an increase in the number of
microglia and macrophages with nuclear immunoreactivity for NF kappa B
in association with HIV-1 encephalitis. NF kappa B positive
multinucleated giant cells were also detected, as were cells which
contained both NF kappa B and HIV-1 antigen. In contrast, the number of
neurons and GFAP-positive astrocytes that were immunoreactive for NF
kappa B was approximately the same in all groups of subjects. These data
are consistent with the hypothesis that persistent, high-level
activation of NF kappa B may promote the sustained production of
neurotoxins by microglia and macrophages during HIV-1 encephalitis.
Adolescence Autopsy AIDS Dementia Complex/METABOLISM/*PATHOLOGY
Brain/METABOLISM/*PATHOLOGY Child Child, Preschool Comparative Study
Female Human HIV Core Protein p24/ANALYSIS HIV Seronegativity *HIV-1
Immunoenzyme Techniques Immunohistochemistry Infant Infant, Newborn
Macrophages/PATHOLOGY Male Microglia/PATHOLOGY Neurons/*PATHOLOGY
NF-kappa B/*ANALYSIS/METABOLISM Putamen/PATHOLOGY Support, Non-U.S.
Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE