UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

The role of HIV-1 in the pathogenesis of cerebral cortical changes in HIV-positive patients: a study using immunohistochemistry and the polymerase chain reaction

Sinclair, Elizabeth; (1993) The role of HIV-1 in the pathogenesis of cerebral cortical changes in HIV-positive patients: a study using immunohistochemistry and the polymerase chain reaction. Doctoral thesis (Ph.D), UCL (University College London). Green open access

[img]
Preview
Text
The_role_of_hiv-1_in_the_patho.pdf

Download (20MB) | Preview

Abstract

The human immunodeficiency virus (HIV-1) is believed to cause neurological dysfunctions, including dementia. Subcortical lesions were originally thought to underlie these problems; however, the recent application of immunohistochemical and morphometric methods has revealed that cortical changes, consisting of a glial cell reaction and a loss of nerve cells, are also present in AIDS. It has even been suggested that these cortical changes are a more likely correlate of dementia, especially since the association between subcortical lesions and dementia "is not entirely convincing. As yet, the existence of HIV-1 within these cortical lesions has not been demonstrated; indeed, viral antigen and nucleic acid are found more often in the white matter than in the cortex. This study attempts to correlate the presence of HIV-1 in the cerebral cortex, with changes in astrocyte and microglial cell density and morphology. The frontal cortex of AIDS patients with and without immunohistochemical evidence of HIV-1 cerebral infection and HIV-1-seropositive non-AIDS brains were compared with normal controls. However, immunohistochemical localisation of HIV-1 may not be optimal. A more sensitive detection technique, the polymerase chain reaction (PCR), was therefore also employed, to detect HIV-1 proviral DNA from the cortex of AIDS and HIV-1-seropositive non-AIDS cases. HIV-1 antigens were found in the cortex of a small proportion of AIDS brains, despite being present the white matter of many cases. In fact, when antigen was 3 detected in the cortex and white matter of the same section, antigen was invariably more abundant in the white matter. In contrast, HIV-1 proviral DNA can be detected in both cortex and white matter of the majority of AIDS patients using PCR. The amount of proviral DNA seems to be equal in both regions, while there is a clear difference in antigen detection. These findings suggest that although both regions are infected, replication of HIV is more restricted in the cortex, than in the white matter. HIV-1 antigen was not detected in any of the HIV-1-seropositive non-AIDS brains; however proviral DNA was detected in 2 out of 8 cases, confirming that HIV- 1 can enter the brain at a relatively early stage of disease. An astroglial reaction was observed in the anterior frontal cortex of the majority of AIDS patients, but not in most of the HIV-1-seropositive non-AIDS. A more subtle microglial cell reaction was also present in many AIDS cases whilst the density of microglial cells was significantly higher in the HIV-1-seropositive non-AIDS cases than the AIDS. However, it was not determined whether this was due to the different risk factors or the stage of disease. The presence of HIV-1 proviral DNA in the cortex of AIDS brains was associated with an increased density of GFAP positive astrocytes and the presence of reactive microglial cells. However these changes also existed, although less severely, in cases from which HIV-1 proviral DNA was not detected. These results suggest that HIV-1 contributes to the glial reaction observed in the cerebral cortex, but is not the only factor involved.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The role of HIV-1 in the pathogenesis of cerebral cortical changes in HIV-positive patients: a study using immunohistochemistry and the polymerase chain reaction
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10122115
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item