PubMed · 8345733
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K Shimada. 1993. [AIDS].. https://doi.org/10.5980/jpnjurol1989.84.991
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Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator protein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of beta-chemokines, which are relatively less selective for monocytes, including RANTES, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the beta-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in the brain and the monocytic infiltration that may substantially contribute to dementia.
OBJECTIVE: Concentrations of quinolinic acid, an N-methyl-D-aspartate agonist, are often elevated for long periods of time in the cerebrospinal fluid (CSF) and brain tissue of patients with AIDS dementia complex (ADC). This study was designed to test the hypothesis that chronic exposure of human neurons to quinolinic acid levels equivalent to those in the CSF of ADC patients is neurotoxic. DESIGN AND METHODS: Human fetal brain 14-16 weeks post-menses was cultured in medium with no detectable levels of quinolinic acid. After 4 weeks, 350 or 1200 nmol/l quinolinic acid was added to the feeding medium for a further 5 weeks. Neurotoxicity was evaluated using immunohistochemistry, transmission and scanning electron microscopy, and image analysis. RESULTS: A total of 1200 nmol/l quinolinic acid caused altered cell associations, a decrease in cell density and decreased microtubule-associated protein (MAP)-2 immunoreactivity compared with cultures exposed to 350 nmol/l quinolinic acid or controls. Image analysis of neurons in randomly selected fields revealed significantly swollen cells (P < 0.0001) compared with those treated with 350 nmol/l quinolinic acid or controls. Dendritic varicosities and discontinuous microtubular arrays were present in neurons exposed to both quinolinic acid concentrations, but not in control cultures. CONCLUSIONS: This study is the first to assess quinolinic acid levels in the experimental medium, and demonstrates that chronic exposure of human neurons to concentrations of quinolinic acid equivalent to those in the CSF of patients with ADC leads to alterations in dendritic ultrastructure and MAP-2 immunoreactivity, which is consistent with ADC pathology.
OBJECTIVE: Neuropathological abnormalities induced by HIV-1 are not always predictable on the basis of the presence of HIV-related neurological symptoms. HIV-1 RNA load was measured in the cerebrospinal fluid (CSF) of HIV-infected patients to verify whether it could be a marker of HIV-induced neuropathology. DESIGN AND METHODS: Histopathological and immunohistochemical examination of the brain for HIV-1 p24 antigen was performed in 50 HIV-infected patients with neurological symptoms; patients were defined as having HIV encephalitis in the presence of HIV-related lesions or HIV-1 p24 antigen-positive cells. Quantitative polymerase chain reaction for HIV-1 RNA was retrospectively applied to CSF samples that had been drawn 1-60 days prior to death from these 50 patients; paired plasma samples of 28 patients were also analysed. RESULTS: The CSF HIV-1 RNA copy numbers were significantly higher in 22 patients with HIV encephalitis than in 28 patients without (median, 4.77 log10 versus 3.45 log10 copies/ml; P = 0.0003). No correlation was found between CSF HIV-1 RNA load and the presence of opportunistic brain pathologies at post-mortem examination or between HIV-1 RNA loads in paired CSF and plasma samples. CONCLUSIONS: High CSF HIV-1 RNA levels are associated with HIV encephalitis, regardless of the presence of opportunistic brain diseases or HIV-1 RNA levels in plasma. Quantitative CSF HIV-1 RNA may therefore be used as a specific marker of HIV-induced neuropathology.