Att drabbas av traumatisk hjärnskada (Traumatic Brain Injury; TBI) innebär att hjärnan utsättas för ett yttre våld som kan orsaka kortvariga samt långvariga funktionsnedsättningar. Det kan medföra livsförsändningar både för den drabbade och för de närstående. Syftet med denna litteraturstudie var att beskriva upplevelsen av att vara närstående till en person med traumatisk hjärnskada. Studien utfördes i form av en litteraturstudie med kvalitativ innehållsanalys som analyserades med manifest ansats där människors upplevelse och erfarenheter var i fokus. I studien inkluderades 13 vetenskapliga artiklar. Under analysprocessen av valda artiklar identifierades sex slutkategorier; Ta ansvar och ge upp sina egna behov, Få förändrade och nya roller, Brist på information från hälso-och sjukvården, Vara psykiskt belastad, känsla av ensamhet och isolering; Förlust av relationer. Resultatet visade att närstående upplevde olika svårigheter relaterade till att leva med en person med traumatisk hjärnskada. Att vara närstående till en person med traumatisk hjärnskada kan skapa ekonomiska, sociala, psykiska, känslomässiga och sexuella konsekvenser vilket medför stora förändringar i sociala roller och relationer. Sjuksköterskor behöver kunskap om hur det är att vara närstående till personer med traumatisk hjärnskada samt ha en förståelse för deras upplevelse för att kunna bemöta dem på ett adekvat sätt. Sjuksköterskans kunskap och förståelse kan förbättra närståendes upplevelse av sjukvården samt att de får stöd i sin situation.

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Traumatic brain injury (TBI) elicits an immediate neuroinflammatory response that involves resident glia and infiltrating peripheral immune cells that coordinate tissue damage and functional deficits. The activation of resident microglial has been associated with a change in their morphology from a branched-like ramified cell to an ameboid state. This activation is thought to initiate a pro-inflammatory response leading to the release of neurotoxic, immune chemoattractant, and antigen-presenting signals. Subsequently, peripheral-derived immune cells (PICs), such as neutrophils and monocytes, travel to the site of injury and help coordinate this response. However, little is known regarding whether PICs influence the progressive activation state of microglia in the acute and chronic phases of injury. Overactivation of microglia can lead to neuroinflammation-mediated tissue damage and death or dysfunction of healthy neurons. Therefore, understanding how microenvironmental cues may regulate the microglial response may aid in strategies to retool their activation state in the brain. EphA4 receptor tyrosine kinase has been identified as a potential cell-to-cell contact protein on PICs that could be involved in the inflammatory changes following TBI. While microglial activation changes have been described in TBI models, the mechanistic role of infiltrating peripheral-derived immune cell (PIC) recruitment on microglial fate and function is not well understood. The purpose of my project is to gain a better understating of the temporospatial influence that EphA4-expressing PICs, specifically monocyte/macrophages, have on microglial proliferation, survival, activation phenotype, and debris clean-up using bone marrow GFP chimeric mice and the cortical contusion injury TBI model. / Doctor of Philosophy / Traumatic brain injury (TBI) triggers an immediate response from the brain's immune system, involving both local glial cells and immune cells from outside the brain. These cells work together to mediate the initial injury but, in some cases, cause development of a secondary injury. Microglia, the brain's resident immune cell, change their shape and behavior when activated by a TBI, becoming more aggressive and releasing inflammatory proteins. At the same time, immune cells from the bloodstream, like neutrophils and monocytes, rush to the injury site to assist. Yet, it's unclear how these immune cells affect microglia over time during the injury's acute and chronic phases. If microglia become too active, they can cause further damage to brain tissue and harm healthy neurons. Therefore, understanding the signals that control microglial activity could help us develop therapies to manage brain inflammation. One protein of interest in this process is the EphA4 receptor found on immune cells, which might play a crucial role in inflammation following TBI. While we know that microglia change post-TBI, we don't fully understand how the recruitment of immune cells from outside the brain affects them. My research aims to clarify how EphA4-expressing immune cells, especially monocytes/macrophages, influence microglia in terms of growth, behavior, and their ability to mediate a TBI.

Traumatic brain injury (TBI) is the most frequent cause of death in children and young adults in the United States. Besides emergency neurosurgical procedures, there are few medical treatment options to improve recovery in people who have experienced a TBI. Management of patients who survive TBI is complicated by both central nervous system and peripheral systemic effects. The pathophysiology of systemic inflammation and coagulopathy following TBI has been attributed to trauma-induced endothelial cell dysfunction; however, there is little knowledge of the mechanisms by which trauma might impact the functions of the vascular endothelium at sites remote from the injury. The endothelium lining these small vessels normally produces nitric oxide (NO), arachidonic acid metabolites, and endothelial-dependent hyperpolarizing factors to relax the surrounding vascular smooth muscle. For this research study we investigated the effects of fluid-percussion-induced TBI on endothelial-dependent vasodilatory functions in a remote tissue bed (the mesenteric circulation) 24 hours after injury. We hypothesized that TBI causes changes in the mesenteric artery endothelium that result in a loss of endothelial-dependent vasodilation. We found that vasodilations induced by the muscarinic-receptor agonist, acetylcholine, are attenuated following TBI. While the endothelial-derived hyperpolarizing component of vasodilation was preserved, the NO component was severely impaired. Therefore, we tested whether the loss of NO component was due to a decrease in bioavailablity of the NO synthase (NOS) cofactor BH4, the NOS substrate L-arginine, or to changes in expression/activity of the enzyme arginase, which competes with NOS for L-arginine. We found that supplementation of L-arginine and inhibition of the enzyme arginase rescues endothelial-dependent vasodilations in TBI arteries. This study demonstrates that there are pathological systemic effects outside the point of injury following TBI leading to a dysfunctional endothelial vasodilatory pathway. These data provide insight into the pathophysiology of endothelial dysfunction after trauma and may lead to new potential targets for drug therapy.

abstract: The objective of this small animal pre-clinical research project was to study quantitatively the long-term micro- and macro- structural brain changes employing multiparametric MRI (Magnetic Resonance Imaging) techniques. Two separate projects make up the basis of this thesis. The first part focuses on obtaining prognostic information at early stages in the case of Traumatic Brain Injury (TBI) in rat animal model using imaging data acquired at 24-hours and 7-days post injury. The obtained parametric T2 and diffusion values from DTI (Diffusion Tensor Imaging) showed significant deviations in the signal intensities from the control and were potentially useful as an early indicator of the severity of post-traumatic injury damage. DTI was especially critical in distinguishing between the cytotoxic and vasogenic edema and in identification of injury regions resolving to normal control values by day-7. These results indicate the potential of quantitative MRI as a clinical marker in predicting prognosis following TBI. The second part of this thesis focuses on studying the effect of novel therapeutic strategies employing dendritic cell (DC) based vaccinations in mice glioma model. The treatment cohorts included comparing a single dose of Azacytidine drug vs. mice getting three doses of drug per week. Another cohort was used as an untreated control group. The MRI results did not show any significant changes in between the two treated cohorts with no reduction in tumor volumes compared to the control group. The future studies would be focused on issues regarding the optimal dose for the application of DC vaccine. Together, the quantitative MRI plays an important role in the prognosis and diagnosis of the above mentioned pathologies, providing essential information about the anatomical location, micro-structural tissue environment, lesion volume and treatment response. / Dissertation/Thesis / Masters Thesis Bioengineering 2014

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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.

Moderate-to-severe traumatic brain injury (M/S TBI) is a growing public health concern with significant impact on the cognitive functioning of survivors. Cognitive control and deficits in awareness have been linked to poor recovery and rehabilitation outcomes. One way to research cognitive control is through awareness of errors using electroencephalogram and event-related potentials (ERPs). Both the error-related negativity and the post-error positivity components of the ERP are linked to error awareness and cognitive control processes. Attentional capacity and levels of apathy influence error awareness in those with M/S TBI. There are strong links between awareness, attention, and apathy. However, limited research has examined the role of attention, awareness, and apathy using electrophysiological indices of error awareness to further understand cognitive control in a M/S TBI sample. The current study sought to elucidate the role of apathy in error awareness in those with M/S TBI. Participants included 75 neurologically-healthy controls (divided randomly into two control groups) and 24 individuals with M/S TBI. All participants completed self-report measures of mood, apathy, and executive functioning, as well as a brief neuropsychological battery to measure attention and cognitive ability. To measure awareness, participants completed the error awareness task (EAT), a modified Stroop go/no-go task. Participants signaled awareness of errors committed on the previous trial. The M/S TBI group decreased accuracy while improving or maintaining error awareness compared to controls over time. There were no significant between-group differences for ERN and Pe amplitudes. Levels of apathy in the M/S TBI group were included in three multiple regression analyses predicting proportion of unaware errors, ERN amplitude, and Pe amplitude. Apathy was predictive of error awareness, although not in the predicted direction. Major analyses were replicated using two distinct control groups to determine potential sample effects. Results showed consistent results comparing both control groups to a M/S TBI group. Findings show variable levels of awareness and accuracy over time for those with M/S TBI when compared to controls. Conclusions include varying levels of attention and awareness from the M/S TBI group over time, evidenced by improving awareness of errors when they are happening, but an inability to regulate performance sufficiently to improve accuracy. Levels of apathy are playing a role in error awareness, however, not in predicted directions. The study provides support for the role of attentional impairments in error awareness and encourages future studies to look for varying levels of performance within a given task when using populations linked to elevated levels of apathy and attentional deficits.

This study presents mathematical surrogate models, derived from finite element kinematic response data, to predict car crash-induced occupant head and neck injury risk for a broad range of impact velocities (10 – 45 mph), impact locations, and angles of impact (-45° to 45°). The development of these models allowed for wide-scale injury prediction while significantly reducing the overall required number of impact test cases. From these, increases in both the impact velocity and the impact’s locational proximity to the occupant were determined to result in the greatest head and neck injury risks. Additionally, strong interactions between the impact orientation variables (location and angle) produced significant changes in the head injury risk, while the neck injury risk was relatively insensitive to these interactions; likely due to the uniaxiality of the current standard neck injury risk metrics. Overall, this methodology showed potential for future applications in wide-scale injury prediction or vehicular design optimization.