Tumor necrosis factor-α, microglia and astrocytes in AIDS dementia complex

The pathogenesis of HIV-associated cognitive changes is poorly understood. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) have been postulated to contribute to the mechanism of the neurological complications of HIV infection. One of the effects of TNF-alpha is to induce astrocyte prolifer...

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Bibliographic Details
Published in:Acta neuropathologica 1997-05, Vol.93 (5), p.508-517
Main Authors: SEILHEAN, D, KOBAYASHI, K, HE, Y, UCHIHARA, T, ROSENBLUM, O, KATLAMA, C, BRICAIRE, F, DUYCKAERTS, C, HAUW, J.-J
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
Adult
AIDS
AIDS Dementia Complex - metabolism
AIDS Dementia Complex - pathology
AIDS Dementia Complex - psychology
AIDS/HIV
Astrocytes
Astrocytes - metabolism
Basal ganglia
Biological and medical sciences
Brain Chemistry - physiology
Cognitive ability
Cortex (frontal)
Cytokines
Dementia
Dementia disorders
Endothelial cells
Glial fibrillary acidic protein
Glial Fibrillary Acidic Protein - metabolism
Gliosis
Gliosis - pathology
Glycoprotein gp41
HIV
HIV Envelope Protein gp41 - metabolism
Human immunodeficiency virus
Humans
Immune response
Immunodeficiencies
Immunodeficiencies. Immunoglobulinopathies
Immunohistochemistry
Immunopathology
Macrophages
Male
Medical sciences
Microglia
Microglia - metabolism
Myelin
Necrosis
Neurological complications
Neurological diseases
Prospective Studies
Substantia alba
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-TNF
Tumor necrosis factor-α
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Summary:The pathogenesis of HIV-associated cognitive changes is poorly understood. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) have been postulated to contribute to the mechanism of the neurological complications of HIV infection. One of the effects of TNF-alpha is to induce astrocyte proliferation in vitro. The purpose of this study was to look for a correlation between the expression of TNF-alpha, astrogliosis and the degree of cognitive impairment in 12 prospectively assessed AIDS cases without focal brain lesion, 8 of whom were demented. They were compared with 6 control patients without neurological disease. Neuropathological examination showed myelin pallor in 5 of the 8 demented patients. TNF-alpha expression was detected by immunohistochemistry in the midfrontal cortex, subcortical and deep white matter, and basal ganglia. Not only perivascular macrophages but also some microglial and endothelial cells were labeled. Most TNF-alpha-positive cells were in close contact with glial fibrillary acidic protein-positive astrocytes. They were more numerous than gp41-positive cells. Their density increased with increasing cognitive impairment and in parallel to the astrogliosis in the frontal cortex, basal ganglia and deep white matter. These findings further support the hypotheses that lesions of the deep white matter, driven by TNF-alpha, are associated with cognitive alteration, and that indirect effects of HIV infection in the brain participate in the development of HIV-associated dementia through a diffuse immune activation, mediated by cytokines.
ISSN:0001-6322
1432-0533
DOI:10.1007/s004010050646