Doctoral Degrees (Clinical Anatomy)

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Browsing Doctoral Degrees (Clinical Anatomy) by browse.metadata.advisor "Muller, Christo J. F."

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    Multi-element analysis of human brain regions
    (Stellenbosch : Stellenbosch University, 2020-04) Cilliers, Karen; Muller, Christo J. F.; Page, Benedict; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Anatomy and Histology.
    ENGLISH ABSTRACT: Trace elements are vital for normal cellular function. An imbalance of these elements can result in oxidative stress and cellular damage, which can contribute to ageing, neurodegenerative diseases and brain tumours. While some neurodegenerative diseases have been thoroughly investigated with regards to trace element imbalance, human immunodeficiency virus (HIV)- associated neurocognitive disorder (HAND) has not been investigated. Chelation or supplementation of trace elements could assist with treating HAND, as has been attempted with Alzheimer’s disease and brain tumours. Additionally, there may exist differences between population groups, sex and brain regional distribution. A trace element imbalance may predispose individuals to neurodegenerative diseases. Therefore, the aim of this study was to determine if HIV, population group (geographical location), sex and anatomical brain regions have an effect on trace element concentrations in the brain. A thorough literature review was conducted, consisting of two literature review chapters and two published systematic reviews. Trace element changes due to ageing and Alzheimer’s disease, as well as brain tumours were reviewed. Furthermore, the effect of HIV on the brain, such as atrophy, diffusion changes, and brain matter hyperintensities, were reviewed to ascertain which brain regions are commonly affected. Since the HIV status of the cadavers is unknown, a published systematic review was included to ascertain the most reliable test, tissue or bodily fluid, as well as the duration that HIV remains reliably detectable after death. Prior to formalin embalming, blood was drawn and tested in triplicate with Determine HIV1/2 rapid tests and confirmed with a SD HIV Device 1/2 3.0 rapid HIV Kit. After embalming, tissue was sampled from the caudate nucleus from HIV-positive and HIV-negative individuals. To determine population group, sex and brain regional differences, samples from the caudate nucleus, putamen, globus pallidus and hippocampus were taken. Trace element concentrations were determined using inductively coupled plasma mass spectrometry. A Kruskal-Wallis test was used to determine statistically significant differences between HIV-positive and HIV negative groups. A multiple median regression model was used to determine significant differences in trace element concentrations between sex and regions. To determine the effect of HIV, 15 HIV-positive and 14 HIV-negative male cadavers were included in the study (mean age 44, range 22 to 61). To determine differences between the population, sex and brain region differences, 29 male and 13 female cadavers from a South African population within the Western Cape region were also included in the study (mean age 35, range 19 to 45). In the HIV-infected group, cadmium was marginally decreased, and nickel was marginally increased. Trace element levels were comparable to other population groups, such as India, the United Kingdom and Canada, although magnesium was considerably lower compared to the literature. While there were no significant sex differences, significant anatomical regional differences existed. Regional distribution of iron, selenium and barium in the brain were consistent with the literature, while zinc, manganese, copper, calcium, magnesium and strontium were inconsistent. In conclusion, the present study provides information for the first time on the alterations of trace element levels in the brains of HIV-infected individuals. More research should be conducted to ascertain the different ways that HIV alters the brain. A larger cohort, including individuals with and without HAND would provide valuable information on trace element content. Additionally, it should be investigated whether chelation or supplementation of trace elements could improve the symptoms of HAND. This is also the first study to report the trace element concentrations of different brain regions from a South African population within the Western Cape region. Currently no studies have been reported in other regions of Africa, and the reasons for the differences between population groups should be explored. Additionally, supplementation could possibly improve the low magnesium levels observed in the brains of individuals from a Western Cape population.