Military-related blast-exposure and sports-related closed-head impact-injury are associated with traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE), a tau protein neurodegenerative disease. Despite growing awareness of links between TBI and CTE, the mechanisms underpinning this association, and relationship to concussive and subconcussive head injury, are poorly understood. This dissertation addresses the hypothesis that blast-exposure and impact-injury induce traumatic acceleration of the head and injurious forces in the brain that led to structural brain damage (TBI) and chronic sequelae, including CTE. This hypothesis was addressed in five specific aims: 1) develop a blast shock tube instrument and impact instrument to deliver relevant blast-exposure and impact-injury to mice, 2) validate a mouse model of single blast-exposure that recapitulates brain pathology in blast-exposed military veterans diagnosed with CTE, 3) validate a mouse model of single-repeat closed-head impact-injury that recapitulates brain pathology in contact sport athletes diagnosed with CTE, 4) match kinematics of blast and impact models using high-speed videography, 5) deploy kinematically-matched mouse models of single blast-exposure and single-repeat closed-head impact-injury to investigate mechanisms that trigger experimental concussion and post-traumatic sequelae. Blast and impact injuries were shown to cause similar CTE-linked brain pathologies, including microvasculopathy, neuroinflammation, astrogliosis, and phosphorylated tauopathy. Despite similarities in chronic consequences, blast-exposure and impact-injury produced different acute neurological responses. Surprisingly, impact-injured mice demonstrated signs of experimental concussion, whereas blast-exposed mice with comparable head kinematics did not. Computational modeling indicated that point loading of forces during impact, as opposed to distributed loading in blast, caused ipsilateral spikes in cortical shear stress which we conclude to be responsible for experimental concussion. The blast-exposure and impact-injury models have been and will continue to be invaluable tools for elucidating the mechanisms of and relationships between concussion, TBI, and CTE. / 2019-07-09T00:00:00Z

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with exposure to repetitive head impacts (RHI) in contact sports. No treatments are currently available. Much of the focus in CTE has been on the microtubule-binding protein tau, which tends to accumulate within neurons and glia around blood vessels at the depths of cortical sulci. The mechanisms of tau accumulation and propagation in CTE are still unknown. The predilection for the perivascular region suggests inherent structural and/or cellular vulnerabilities in this area. Astrocytes are glial cells in this perivascular region that help form the blood brain barrier (BBB) and the neurovascular unit (NVU). Their endfeet envelop blood vessels and help transport nutrients from the blood into the brain, as well as clear harmful waste products out of the brain. Astrocytes are also vital players in many of the brain’s other normal physiological functions, including providing structural and metabolic support to neurons and maintenance of ion and water homeostasis. In response to injury or disease, astrocytes undergo a series of structural and functional changes in a process known as reactive astrogliosis. Astrogliosis is widely considered a hallmark of brain pathology, however, only recently have we begun to understand its functional implications. Astrocytes can respond heterogeneously to CNS insults, including either loss or increase of homeostatic functions, or gain of new, possibly toxic functions. These different astrocytic responses can either assist in recovery or further exacerbate injury. Our current understanding of how astrocytes are altered in RHI and CTE is limited. A degenerative phenotype has been identified in older donors with later stage CTE, but its presence in younger donors with earlier stage disease is unknown. The hypothesis of this study is that exposure to repetitive head trauma causes astrocytes to become reactive and adopt altered phenotypes, including loss of homeostatic functions, in brain areas known to be biomechanically susceptible to the shearing forces of head trauma, such as the perivascular region and interface of the grey and white matter at the depth of the cortical sulcus. These altered phenotypes are expected to be found in athletes with and without pathological tau deposition, highlighting astrocytes as potential therapeutic targets in the post-traumatic injury cascade. Specifically, I seek to characterize reactive astrocyte phenotypes and assess changes in their perivascular function in the brains of former American football players with and without a neuropathological diagnosis of CTE.

This thesis explores how traumatic memories of the Tangshan earthquake have been constructed in literature, documentary works, and films. Through analyzing the narrative construction of the Tangshan earthquake in the form of film and literature, this thesis studies the relationship between state power and individual agency in the representation of this natural disaster. It argues that the cultural representation of this natural disaster reflects a subtle shift: one from the dominant nationalistic narrative to the narrative centering on individuals’ psychological trauma. It suggests the high degree of state control and politicization is what is similar between a natural disaster such as the Tangshan earthquake and other political events. To some extent, the Tangshan earthquake has become a political event to promote the Chinese Communist Party’s (CCP) propaganda. Therefore, this thesis engages existing scholarship on political traumas to research the Tangshan earthquake. It is indicating a subtle shift because it is a slow-changing process and there is no mark to signal a radical departure from the earlier nationalism accounts. There also exists more interlaces and interconnections between the state and individual in the range of sources I have examined. And the overlay of the different narratives reflects the complexity of reality and history.

Thesis (MA)-- Stellenbosch University, 2014. / ENGLISH ABSTRACT: Family caregivers play a large role in the lives of traumatic brain injury (TBI) survivors. This study explored the experiences of family members who care for TBI survivors in the Western Cape. Emphasis was placed on the challenges and resources that were associated with the caregiving role. A qualitative exploratory research design was implemented, whereby thematic analysis was utilised to examine the semi-structured interviews that were conducted with 12 female family caregivers of TBI survivors. Several challenges emerged, namely trauma, consequences of a TBI, responsibilities, lack of support, unawareness, financial burden, emotional challenges and coping. Several resources were also identified, namely the road to recovery, social support, financial resource and coping. These findings suggest that although caregivers who care for a family member who sustained a TBI face several challenges through the caregiving task, these individuals have a number of resources that help them to cope. Interventions that focus on psycho-education have been identified as an important need amongst the participants of this study. In addition, the need for support groups were highlighted as an important way in which many of the challenges that these caregivers experience could be addressed. Caregivers also expressed a need for more active involvement of health care professionals with regard to the provision of guidance, empathy and information. It seems as if the caregivers view the relationship between themselves and the health care professionals involved in the treatment of their family member who sustained a TBI as very important. It was however evident from the findings of this study that the caregivers are generally not satisfied with the quality of the interaction between the health care professionals and themselves. This study’s findings serve as a basis for future research studies on the experiences of family caregivers of TBI survivors in the Western Cape. / AFRIKAANSE OPSOMMING: Gesinsversorgers speel ’n groot rol in die lewens van oorlewendes van traumatiese breinbeserings (TBB). Hierdie studie het die ervaringe van gesinsversorgers van TBB-oorlewendes in die Wes-Kaap verken. Die fokus is op die uitdagings en hulpbronne wat geassosieer word met die versorgingsrol. ’n Kwalitatiewe ontwerp is geïmplementeer, waarby tematiese analise gebruik is om die semigestruktureerde onderhoude van 12 vroulike gesinsversorgers van TBB-oorlewendes te bestudeer. Verskeie uitdagings het na vore gekom, naamlik trauma, gevolge van TBB, verantwoordelikhede, gebrek aan ondersteuning, onbewustheid, finansiële las, emosionele uitdagings en hantering. Die hulpbronne wat geïdentifiseer is, het die pad na herstel, sosiale ondersteuning, finansiële hulpbron en hantering ingesluit. Intervensies wat fokus op psigo-opvoeding is geïndentifiseer as ’n belangrike behoefte onder die deelnemers aan die studie. Hierbenewens is ook ’n behoefte aan ondersteuningsgroepe uitgelig as ’n belangrike wyse om die vele uitdagings wat hierdie versorgers ervaar aan te pak. Die versorgers het ook ’n behoefte ervaar aan meer aktiewe betrokkenheid van gesondheidskundiges ten opsigte van die voorsiening van leiding, empatie en inligting. Dit blyk dat versorgers die verhouding tussen hulself en die gesondheidskundiges betrokke by hul gesinslid met die TBB as belangrik beskou. Desnietemin blyk dit duidelik uit die bevindinge van hierdie studie dat versorgers oor die algemeen nie tevrede is met die kwaliteit van die interaksie tussen die gesondheidskundiges en hulself nie. Die bevindinge van hierdie studie dien as basis vir toekomstige navorsing oor die ervaringe van gesinsversorgers van TBB-oorlewendes in the Wes-Kaap.

Thesis (MA (Theol.))-University of Pretoria, 2007. / Includes bibliographical references.

This study discusses the assessment and treatment of a 21-year old male who had suffered multiple traumas, which had culminated in the death of his younger brother. He presented with Acute Stress Disorder. The literature review examines a diverse range of theorists and discourses, that have addressed the psychological consequences of trauma and highlights the complexity of the phenomena involved. The case study, located in the South African context, aims to sensitise the reader to the unique dilemmas facing each trauma survivor, and serves to highlight specifically those areas, which are pertinent and further more contribute significantly to the recovery process. The case narrative consists of a detailed synopsis of the therapy process, extracted from the session record notes documented at the time. Several other sources of information, including contributions from the participant, were used to verify and validate the accuracy of the data included. The narrative is written in a style that conveys the intensity of the nature of trauma work and the manner in which both patient and clinician are frequently confronted with very difficult emotional work. Finally the discussion examines the case narrative through the use of a set of carefully selected hermeneutic questions. These focused on (I) key concepts from the work of Robert Lifton who highlights the existential dimensions of the impact of trauma; (2) the role of the image in encapsulating the complex traumatic and post-traumatic experience of the survivor as well as facilitating the emotional processing of the trauma is examined; (3) the contribution to the process of therapy of aspects of the therapeutic relationship; and (4) the concept of recovery in relation to the question of what constitutes 'trauma work'. In conclusion, several meta-theoretical issues related to trauma, the strengths and weaknesses inherent to the research and relevant future areas of research are highlighted.

No description available.

Thesis (MA)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: Posttraumatic stress Disorder (PTSD) has been researched and written about since its recognition as a disorder in the DSM-III in 1980. This study reviews the literature on PTSD and cognitive behavioural therapies, designed for its treatment. It covers the historical aspects of how the syndrome came to be identified, defined and recognized as a discrete disorder. The neurobiological features of the disorder, its cognitive processes, particularly those of dissociation and traumatic memory are dealt with. Cognitive behavioural therapies are reviewed, these include: relaxation; hypnosis; exposure; eye movement desensitization reprocessing; anxiety management training; cognitive therapy and combination therapies. Further areas for research are suggested based on the lacunae that have yet to be explored with regard to cognitive behavioral therapy treatments. / AFRIKAANSE OPSOMMING: Posttraumatiesestressversteuring is nagevors en bespreek vandat dit in 1980 in die DSM-III as 'n versteuring herken is. Hierdie studie gee 'n oorsig van die literatuur oor PTSVen kognitiewe gedragsterapeutiese, ontwerp om dit te behandel. Dit gee 'n historiese oorsig van hoe dit geïdentifiseer, beskryf en gedefinieër is as 'n spesifieke gedragsversteuring. Die neurobiologiese implikasies van die versteuring, die kognitiewe kenmerke, veral die van dissosiasie en traumatiese geheue word ondersoek. Kognitiewe gedragsterapieword beskryf en sluit die volgende in: ontspanning; blootstelling, oogbewegingdesensiteringherprosering; angsbeheeropleiding; kognitiewe terapie en kombinasie terapie. Verdere areas vir navorsing word voorgestel en is gebasseer op die gebrekke wat bestaan in kognitiewebedragsterapie.

ABSTRACT: During inflammation, the kynurenine pathway (KP) metabolises the essential amino acid tryptophan (TRP) potentially contributing to excitotoxicity via the release of quinolinic acid (QUIN) and 3-hydroxykynurenine (3HK). Despite the importance of excitotoxicity in the development of secondary brain damage, investigations on the KP in TBI are scarce. In this study, we comprehensively characterised changes in KP activation by measuring numerous metabolites in cerebrospinal fluid (CSF) from TBI patients and assessing the expression of key KP enzymes in brain tissue from TBI victims. Acute QUIN levels were further correlated with outcome scores to explore its prognostic value in TBI recovery. METHODS: Twenty-eight patients with severe TBI (GCS ≤ 8, three patients had initial GCS = 9-10, but rapidly deteriorated to ≤8) were recruited. CSF was collected from admission to day 5 post-injury. TRP, kynurenine (KYN), kynurenic acid (KYNA), QUIN, anthranilic acid (AA) and 3-hydroxyanthranilic acid (3HAA) were measured in CSF. The Glasgow Outcome Scale Extended (GOSE) score was assessed at 6 months post-TBI. Post-mortem brains were obtained from the Australian Neurotrauma Tissue and Fluid Bank and used in qPCR for quantitating expression of KP enzymes (indoleamine 2,3-dioxygenase-1 (IDO1), kynurenase (KYNase), kynurenine amino transferase-II (KAT-II), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilic acid oxygenase (3HAO) and quinolinic acid phosphoribosyl transferase (QPRTase) and IDO1 immunohistochemistry. RESULTS: In CSF, KYN, KYNA and QUIN were elevated whereas TRP, AA and 3HAA remained unchanged. The ratios of QUIN:KYN, QUIN:KYNA, KYNA:KYN and 3HAA:AA revealed that QUIN levels were significantly higher than KYN and KYNA, supporting increased neurotoxicity. Amplified IDO1 and KYNase mRNA expression was demonstrated on post-mortem brains, and enhanced IDO1 protein coincided with overt tissue damage. QUIN levels in CSF were significantly higher in patients with unfavourable outcome and inversely correlated with GOSE scores. CONCLUSION: TBI induced a striking activation of the KP pathway with sustained increase of QUIN. The exceeding production of QUIN together with increased IDO1 activation and mRNA expression in brain-injured areas suggests that TBI selectively induces a robust stimulation of the neurotoxic branch of the KP pathway. QUIN's detrimental roles are supported by its association to adverse outcome potentially becoming an early prognostic factor post-TBI.

This dissertation is about how the concept of harm, damage or wound is applied as a metaphor to a site often called the self or the soul. This is the social space of the individual subject, which is, paradoxically, placed by our language and culture in a person’s interior – a place where we are all said to be vulnerable and endangered by a potentially hostile environment. The thesis consists of a series of studies which are designed to show how the concept of harm to an inner life emerges from different discursive contexts, and how it does so in distinctly variable versions: psychological, emotional, neurological or social, in more or less stable hybrid forms. Using primary sources which are mostly documentary, supported by some interviews, the studies range from a look at the psychiatric history of post traumatic stress disorder (PTSD) and at the story of its rewriting in English tort law; the recent reprised popularity of attachment theory and its marriage to neurology and a look at the career of the concept of the emotional abuse of children as a social problem category in the legal/administrative processes of Child Protection. These are introduced by a first chapter which concentrates on the metaphoric content of invisible wounds or psychic trauma and the way it produces particular forms of the self. The studies which follow this are clustered around the literature and practices of the psychiatric, psychological, psycho-analytic, social work and legal professions, in order to show how the work of these professionals makes the concept of a psychic injury visible, discussible, treatable, administrable and justiciable. Through their efforts, it is argued, the concept moves from being a metaphor, hooked onto the palpable reality of a physical wound, to acquire a ‘facticity’ of its own; it becomes a reality through its achieved status as a social problem category and an ever present risk to self and self regulation at the turn of the 21st century.