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Multi-element analysis of human brain regions
Thesis (PhD)--Stellenbosch University, 2020.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2020
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| _version_ | 1867614136008966144 |
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| access_status_str | Open Access |
| author | Cilliers, Karen |
| author2 | Muller, Christo J. F. |
| author_browse | Cilliers, Karen Muller, Christo J. F. |
| author_facet | Muller, Christo J. F. Cilliers, Karen |
| author_sort | Cilliers, Karen |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2020. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/108339 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:47:14.419Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2020 |
| publishDateRange | 2020 |
| publishDateSort | 2020 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/108339 Multi-element analysis of human brain regions Cilliers, Karen Muller, Christo J. F. Page, Benedict Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Anatomy and Histology. Trace elements -- Analysis Nervous system -- Degeneration HIV-positive persons UCTD Thesis (PhD)--Stellenbosch University, 2020. 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. AFRIKAANSE OPSOMMING: Spoorelemente is noodsaaklik vir normale sellulêre funksie. 'n Wanbalans van hierdie elemente lei tot oksidatiewe spanning en sellulêre skade, wat kan bydra tot veroudering, neurodegeneratiewe siektes en breingewasse. Alhoewel sommige neurodegeneratiewe siektes deeglik ondersoek is met betrekking tot ‘n wanbalans in spoorelemente, is die verwantskap met menslike immuniteitsgebreksvirus (MIV)-geassosieerde neurokognitiewe versteuring (MGNV) nie deeglik geondersoek nie. Chelasie of aanvulling van spoorelemente kan help met die behandeling van MGNV, soos gepoog is vir Alzheimer se siekte en breingewasse. Daar kan ook ‘n verskil wees tussen bevolkingsgroepe, geslag en breinstreke. ‘n Individu kan meer geneig wees om neurodegeneratiewe siektes op te doen indien daar 'n wanbalans van sekere spoorelemente is. Dus, was die doel van hierdie studie om te bepaal of MIV, bevolkingsgroep (bepaal volgens geografiese ligging), geslag en anatomiese breinstreke 'n invloed het op die spoorelement konsentrasies in die brein. 'n Deeglike literatuuroorsig was uitgevoer, wat bestaan het uit twee literatuuroorsig hoofstukke en twee gepubliseerde sistematiese oorsigte. Die verandering van spoorelemente as gevolg van veroudering en Alzheimer se siekte, sowel as breingewasse was gehersien. Verder is die effek van MIV op die brein, soos atrofie, diffusieveranderinge, en hiperintensiteit in die brein nagegaan om vas te stel watter breinstreke beinvloed word. Aangesien die MIV-status van die kadavers nie bekend was nie, is 'n gepubliseerde sistematiese oorsig ingesluit om die betroubaarste toets, weefsel of liggaamsvloeistof te bepaal, asook die tydsduur wat MIV betroubaar opspoorbaar kan word na dood. Voordat kadavers gebalsem was met formalien, is bloed getrek en in drievoud getoets met Determine HIV-1/2 rapid tests en bevestig met 'n SD HIV Device 1/2 3.0 rapid HIV Kit. Na balseming is weefsel uit die stert kern geneem vanaf MIV-positiewe en MIV-negatiewe individuele. Om die populasiegroep-, geslags- en verspreiding van breinstreke te bepaal, is weefsel van die stert kern, putamen, globus pallidus en hippokampus geneem. Spoorelement konsentrasies was bepaal deur induktief gekoppelde plasmamasspektrometrie. 'n KruskalWallis-toets is gebruik om statisties beduidende verskille tussen MIV-positiewe en MIVnegatiewe groepe te bepaal. 'n Meervoudige mediaan regressiemodel is gebruik om beduidende verskille in element konsentrasies tussen geslag en breinstreke te bepaal. Om die effek van MIV te bepaal, is 14 MIV-negatiewe en 15 MIV-positiewe manlike kadavers gebruik in die studie (gemiddelde ouderdom 44, tussen 22 en 61). Om die verskille tussen bevolkingsgroep, geslag en breinstreke te bepaal, is 29 manlike en 13 vroulike kadavers van ‘n Suid-Afrikaanse bevolking binne die Wes-Kaap ook ingesluit in die studie (gemiddelde ouderdom 35, tussen 19 en 45). In die MIV-geïnfekteerde groep het kadmium effens afgeneem en nikkel het effens vermeerder. Spoorelement konsentrasies was vergelykbaar met ander bevolkingsgroepe, insluitend die van Indië, die Verenigde Koninkryk en Kanada, alhoewel magnesium aansienlik laer was in vergelyking met die literatuur. Alhoewel daar geen noemenswaardige geslagsverskille was nie, was daar beduidende verskille in anatomiese breinstreke. Die verspreiding van yster, selenium en barium in die breinstreke stem ooreen met die literatuur, terwyl sink, mangaan, koper, kalsium, magnesium en strontium strydig was. Ten slotte, die huidige studie verskaf inligting vir die eerste keer oor die veranderinge in spoorelement konsentrasies in die brein van MIV-geïnfekteerde individuele. Meer navorsing moet gedoen word om vas te stel hoe MIV die brein affekteer. ‘n Studie met ‘n groter getal individue, met en sonder MGNV, sal waardevolle inligting verskaf van spoorelement konsentrasies. Daar moet ook ondersoek word of chelasie of aanvulling van spoorelemente die simptome van MGNV kan verbeter. Hierdie is die eerste studie wat die spoorelement konsentrasies van breinstreke uit individuele van 'n Suid-Afrikaanse bevolking in die WesKaap rapporteer. Geen studies in ander streke van Afrika is al gepubliseer nie, en redes vir die verskille tussen bevolkingsgroepe behoort ook ondersoek word. Magnesium aanvulling kan moontlik die laë magnesiumvlakke in die breine van die Wes-Kaapse bevolking groep verbeter. Doctoral 2020-01-14T07:03:26Z 2020-04-28T15:10:19Z 2020-01-14T07:03:26Z 2020-04-28T15:10:19Z 2020-04 Thesis http://hdl.handle.net/10019.1/108339 en_ZA Stellenbosch University xvii, 158 pages application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Trace elements -- Analysis Nervous system -- Degeneration HIV-positive persons UCTD Cilliers, Karen Multi-element analysis of human brain regions |
| title | Multi-element analysis of human brain regions |
| title_full | Multi-element analysis of human brain regions |
| title_fullStr | Multi-element analysis of human brain regions |
| title_full_unstemmed | Multi-element analysis of human brain regions |
| title_short | Multi-element analysis of human brain regions |
| title_sort | multi element analysis of human brain regions |
| topic | Trace elements -- Analysis Nervous system -- Degeneration HIV-positive persons UCTD |
| url | http://hdl.handle.net/10019.1/108339 |
| work_keys_str_mv | AT cillierskaren multielementanalysisofhumanbrainregions |