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Exploring the proteomic landscape of traumatic brain injury models
Thesis (MSc)--Stellenbosch University, 2025.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : Stellenbosch University
2025
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| _version_ | 1867614017744273408 |
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| access_status_str | Open Access |
| author | Vorster, Melissa Sona |
| author2 | Patterton, Hugh George |
| author_browse | Patterton, Hugh George Vorster, Melissa Sona |
| author_facet | Patterton, Hugh George Vorster, Melissa Sona |
| author_sort | Vorster, Melissa Sona |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2025. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/132003 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:45:21.489Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/132003 Exploring the proteomic landscape of traumatic brain injury models Vorster, Melissa Sona Patterton, Hugh George Tabb, David Lee Loos, Ben Eckert, Stephan Stellenbosch University. Faculty of Science. Centre for Bioinformatics and Computational Biology. Proteomics Brain -- Wounds and injuries -- Pathophysiology Traumatic brain injury -- Molecular aspects Brain damage -- Treatment UCTD Thesis (MSc)--Stellenbosch University, 2025. Vorster, M. S. 2025. Exploring the proteomic landscape of traumatic brain injury models. Unpublished masters thesis. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/b4b08b27-8491-4e79-bd70-02e22f04324a ENGLISH ABSTRACT: Background: Traumatic brain injury (TBI) is a multifaceted condition characterized by primary and secondary injury mechanisms, leading to significant molecular and cellular disruptions. Understanding these processes at the proteomic level is critical for developing targeted therapeutic strategies. Systematic reviews and meta-analyses can provide insights into the broader landscape of TBI research, while experimental comparisons of TBI models can refine our understanding of their relevance to human pathology. Research Gap: Current models fail to capture the full complexity of human TBI, particularly the interplay between biochemical and biomechanical mechanisms. Comparative analyses of TBI models and integrative proteomic studies remain limited. Objective: This study aimed to integrate findings from a systematic review, conduct a meta-analysis of publicly available proteomic datasets, and evaluate two chemical TBI models, sodium dithionite (SDT) and 2-deoxy-D-glucose (2DG), to better understand TBI-associated proteomic changes. Method: A systematic review and meta-analysis identified key proteins and pathways altered in TBI. Proteomic analyses of SDT and 2DG models were conducted to assess their ability to replicate TBI pathologies, including oxidative stress, apoptosis, autophagy, and metabolic dysfunction. Comparative analyses explored shared and distinct molecular responses. Key Findings: The systematic review and meta-analysis identified critical proteins and pathways linked to oxidative stress, mitochondrial dysfunction, and cell death. SDT induced oxidative stress and excitotoxicity, while 2DG disrupted metabolic pathways and caused energy depletion. Both models showed overlapping responses, such as inflammation and mitochondrial dysfunction, and distinct pathway activations. Limitations included the inability of chemical models to replicate biomechanical injury, the static nature of proteomic analyses, and incomplete metadata affecting reproducibility. Implications: By combining systematic review, meta-analysis, and experimental model comparison, this study offers a comprehensive framework for understanding TBI at the proteomic level. These findings highlight the strengths and limitations of current models and inform future research directions, including integrating mechanical and chemical models, employing longitudinal and multi-omics approaches, and improving metadata reporting and experimental validation. This approach will enhance the translational relevance of findings and support the development of targeted therapies and biomarkers to improve TBI management and outcomes. AFRIKAANSE OPSOMMING: gtergrond: Traumatiese breinbesering (TBB) is 'n komplekse toestand wat gekenmerk word deur primêre en sekondêre beseringsmeganismes, wat lei tot beduidende molekulêre en sellulêre ontwrigtings. Om hierdie prosesse op die proteomiese vlak te verstaan, is van kardinale belang vir die ontwikkeling van geteikende terapeutiese strategieë. Sistematiese oorsigte en meta-analises kan insig bied in die breër landskap van TBI-navorsing, terwyl eksperimentele vergelykings van TBB-modelle ons begrip van hul relevansie tot menslike patologie kan verfyn. Navorsingsgaping: Huidige modelle slaag nie daarin om die volle kompleksiteit van menslike TBB vas te vang nie, veral nie die interaksie tussen biochemiese en biomeganiese meganismes nie. Vergelykende analises van TBB-modelle en integrerende proteomiese studies is steeds beperk. Doelwit: Hierdie studie het ten doel gehad om bevindings uit 'n sistematiese oorsig te integreer, 'n meta- analise van openbare proteomiese datastelle uit te voer, en twee chemiese TBB-modelle, Natriumdisioniet (SDT) en 2-Deoxy-D-Glukose (2DG), te evalueer om TBB-verwante proteomiese veranderinge beter te verstaan. Metode: 'n Sistematiese oorsig en meta-analise het sleutelpanele en -paaie geïdentifiseer wat verander is in TBB. Proteomiese analises van die SDT- en 2DG-modelle is uitgevoer om hul vermoë te beoordeel om TBB-patologieë, insluitend oksidatiewe stres, apoptose, outofagie en metaboliese disfunksie, na te boots. Vergelykende analises het gedeelde en onderskeidende molekulêre reaksies ondersoek. Sleutelbevindings: Die sistematiese oorsig en meta-analise het kritieke proteïene en paaie geïdentifiseer wat gekoppel is aan oksidatiewe stres, mitochondriale disfunksie en seldood. SDT het oksidatiewe stres en eksitotoksisiteit geïnduseer, terwyl 2DG metaboliese paaie ontwrig en energietekort veroorsaak het. Beide modelle het oorvleuelende reaksies getoon, soos inflammasie en mitochondriale disfunksie, sowel as unieke aktiverings van paaie. Beperkings het die onvermoë van chemiese modelle om biomeganiese beserings na te boots, die statiese aard van proteomiese analises, en onvolledige metadata wat reproduseerbaarheid beïnvloed, ingesluit. Implikasies: Deur sistematiese oorsig, meta-analise en eksperimentele modelvergelyking te kombineer, bied hierdie studie 'n omvattende raamwerk vir die begrip van TBB op die proteomiese vlak. Hierdie bevindings beklemtoon die sterkpunte en beperkings van huidige modelle en rig toekomstige navorsingsrigtings, insluitend die integrasie van meganiese en chemiese modelle, die gebruik van longitudinale en multi-omiese benaderings, en die verbetering van metadata-rapportering en eksperimentele validering. Hierdie benadering sal die translasionele relevansie van bevindings verbeter en die ontwikkeling van geteikende terapieë en biomerkers ondersteun om TBB-bestuur en -uitkomste te verbeter. Masters 2025-05-15T13:44:54Z 2025-05-15T13:44:54Z 2025-03 Thesis https://scholar.sun.ac.za/handle/10019.1/132003 en Stellenbosch University x, 108 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Proteomics Brain -- Wounds and injuries -- Pathophysiology Traumatic brain injury -- Molecular aspects Brain damage -- Treatment UCTD Vorster, Melissa Sona Exploring the proteomic landscape of traumatic brain injury models |
| title | Exploring the proteomic landscape of traumatic brain injury models |
| title_full | Exploring the proteomic landscape of traumatic brain injury models |
| title_fullStr | Exploring the proteomic landscape of traumatic brain injury models |
| title_full_unstemmed | Exploring the proteomic landscape of traumatic brain injury models |
| title_short | Exploring the proteomic landscape of traumatic brain injury models |
| title_sort | exploring the proteomic landscape of traumatic brain injury models |
| topic | Proteomics Brain -- Wounds and injuries -- Pathophysiology Traumatic brain injury -- Molecular aspects Brain damage -- Treatment UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/132003 |
| work_keys_str_mv | AT vorstermelissasona exploringtheproteomiclandscapeoftraumaticbraininjurymodels |