In this PhD thesis, the lives and experiences of a group of combat veterans who began surfing following their return from war are explored. Having encountered life changing traumatic events and experienced much suffering (with many becoming diagnosed with post-traumatic stress disorder), these veterans joined an ex-services charity called Surf Action where they were introduced to surfing alongside other veterans who shared their suffering. The purpose of this research is to explore the effects of surfing and, more broadly, of participation in the charity Surf Action in the veterans lives and on their well-being. It is the first in-depth qualitative investigation of surfing in the lives of combat veterans. Using a combination of life history interviews and participant observation, I collected and analysed stories from the veterans about their lived experiences. Through rigorously applying the innovative analytical approach of dialogical narrative analysis (Frank, 2010, 2012), also inspired by phenomenology, the effects of the veterans stories both on and for their lives and well-being are examined. The analysis first demonstrates that stories of surfing were focused on the veterans physical and sensory interactions with the ocean environment, and helped to cultivate the notion of embodied respite from suffering. It is then suggested that by telling and enacting a collective story, the veterans at Surf Action (the Combat Surfers ) created a therapeutic community through which they accessed mutual support, recreated positive military identities associated with camaraderie, and legitimised their struggles with PTSD. Next, the masculine performances which shaped the veterans actions and narratives around help-seeking and dealing with PTSD are highlighted. Furthermore, the analysis reveals the meanings associated with moving beyond the chaotic influence of trauma in the veterans lives and suggests ways of keeping well following trauma and PTSD. The thesis also incorporates an ethnographic creative non-fiction as a way of enhancing knowledge translation and facilitating wider impact and dissemination of the findings. Finally, the thesis concludes with empirical, theoretical, methodological, and practical implications of the research, with an emphasis throughout on what to the study adds to knowledge. The potential of surfing to contribute to veterans healthcare is discussed alongside recommendations for the charity Surf Action and future possibilities for expanding this research.

Objectives: There is evidence that childhood traumatic brain injury (TBI) is associated with increased risk of offending and violent crime. This study aimed to explore associations between TBI in a group of delinquent and vulnerable young people (VYP) at risk of offending, and facial emotion recognition (FER) abilities, inhibition control (Stop-IT) and self-reported reactive-proactive aggression (RPQ). Methods: There were two studies. The first study used a cross sectional between group design to compare 45 VYP (with and without TBI) and a control group of 59 students on FER task measuring emotion recognition accuracy of six basic emotions. The second study examined differences between TBI and non-TBI groups in the VYP sample (N=21) on a Stop-IT task, FER accuracy and self-reported reactive-proactive aggression. Results: A history of TBI was reported by 60% of the VYP group (48.9% with loss of consciousness [LoC]), whereas 30% of the control group reported a history of TBI (25.4% with LoC). The VYP group (with and without TBI) demonstrated a similar pattern of reduced overall FER accuracy that was significantly different to the control group. Compared to the control group, The VYP groups (with and without TBI) were less accurate on recognising anger, disgust, sadness and surprise, but not happy and fear. There were no significant differences between the TBI- and non-TBI groups. The second study did not find any significant differences between the TBI and non-TBI groups on overall FER accuracy, Stop-IT performance, and RPQ scores. There were also no significant associations between these measures. Conclusions: Future research requires larger samples that enable investigating the association between different severity of TBI, FER and inhibition control ability. Better and more youth-friendly measures are also needed.

Introduction: Annually, an estimated 2.5 million traumatic brain injuries (TBI) occur in the United States, of which, over 50,000 result in deaths. Currently, 5.3 million Americans are living with neurological dysfunction secondary to TBIs leading to a $60 billion dollar cost in medical expenses and productivity losses. To date, there are limited treatments available to cure or ease the morbidity of TBI. Despite preventative efforts, traumatic brain injuries (TBI) occur at a staggering rate and it is estimated that 15-20% of survivors develop persistent post-traumatic neurological impairment. The purposed source of neurological dysfunction is a result of circuit reorganization when the brain rebuilds itself. After diffuse TBI, rodents have been shown to develop a late-onset, gain-of-function sensory sensitivity to whisker stimulation; similar to phonophobia and photophobia experienced by human TBI survivors. This morbidity coincides with evidence of post-TBI circuit reorganization, however the etiology of post-traumatic neurological impairment remains largely unknown. Thrombospondin-1 (TSP-1) and thrombospondin-2 (TSP-2) are heavily expressed during pediatric neuronal synapse development. Expression of TSPs, however declines with age. Mechanistically during development, TSP mediates synaptogenesis via bindingα2δ-1 subunit of the voltage-gated calcium channel receptor (α2δ-1). After neurological insult, re-expression of TSPs has been demonstrated and experimental modulation of the TSP/α2δ-1 interaction has led to changes in morbidity. We therefore hypothesize that experimental diffuse TBI will result in re-expression of TSPs, which will be synchronous with increases in synaptic markers in the thalamocortical whisker circuit. Methods: Adult male Sprague-Dawley rats underwent sham or moderate midline fluid percussion brain injury. At multiple time points over 2-months post-injury, expression of TSPs and synaptic markers were quantified from thalamocortical circuit (ventroposterior medial thalamus (VPM), primary somatosensory barrel fields (S1BF)) biopsies using qPCR and automated capillary westerns, respectively. Results: TSP-1 gene expression and protein levels increase in the VPM during the first week after injury. Gene expression of TSP-1 did not significantly change over time in the S1BF, however, there was a significant increase in protein levels in the first and second weeks after injury. No significant changes were demonstrated in synaptic markers in the VPM over the time course. TSP-1 protein levels demonstrated a similar multimodal response to synaptic markers in the S1BF.Conclusion: Re-expression of TSP-1 and synchronous changes in synaptic marker supports a role for TSP-1 mediated synaptogenesis after experimental diffuse TBI in the S1BF. These data positions us for future investigation of pharmacological inhibition of TSP-mediated synaptogenesis after TBI; which may represent a prophylactic strategy against circuit reorganization and neurological dysfunction after TBI.

Background: Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation. Results: To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an acute time course. In a second cohort, peripheral inflammation was induced seven days after surgery/injury with an intraplantar injection of carrageenan. This was followed by measurement of mechanical hyperalgesia, glial fibrillary acidic protein and Iba1 immunohistochemical analysis of neuroinflammation in the brain, and flow cytometric analysis of T-cell differentiation in mucosal lymph. Traumatic brain injury increased interleukin-6 and chemokine ligand 1 levels in the cortex and serum that peaked within 1-9 h and then resolved. Intraplantar carrageenan produced mechanical hyperalgesia that was potentiated by traumatic brain injury. Further, mucosal T cells from brain-injured mice showed a distinct deficiency in the ability to differentiate into inflammation-suppressing regulatory T cells (Tregs). Conclusions: We conclude that traumatic brain injury increased the inflammatory pain associated with cutaneous inflammation by contributing to systemic immune dysregulation. Regulatory T cells are immune suppressors and failure of T cells to differentiate into regulatory T cells leads to unregulated cytokine production which may contribute to the potentiation of peripheral pain through the excitation of peripheral sensory neurons. In addition, regulatory T cells are identified as a potential target for therapeutic rebalancing of peripheral immune homeostasis to improve functional outcome and decrease the incidence of peripheral inflammatory pain following traumatic brain injury.

published_or_final_version / abstract / Social Work and Social Administration / Doctoral / Doctor of Philosophy

Traumatic brain injury (TBI) is a devastating health problem based on its high incidence, economic burden, and lack of effective pharmacological treatment. Individuals who suffer an injury often experience lifelong disability. TBI results in abrupt, initial cell damage leading to delayed neuronal death. The calcium-activated proteases, calpains, are known to contribute to this secondary neurodegenerative cascade. Prolonged activation of calpains results in proteolysis of numerous cellular substrates including cytoskeletal components, membrane receptors, and cytosolic proteins, contributing to cell demise despite coincident expression of calpastatin, the specific inhibitor of calpains. A comprehensive analysis using two separate calpastatin transgenic mouse lines was performed to test the hypothesis that calpastatin overexpression will reduce posttraumatic calpain activity affording neuroprotection and behavioral efficacy. Increased calpastatin expression was achieved using transgenic mice that overexpress the human calpastatin (hCAST) construct under control of a neuron-specific calcium-calmodulin dependent kinase II alpha or a ubiquitous prion protein promoter. Both transgenic lines exhibited enhanced calpastatin expression within the brain, extending into peripheral tissues under the prion protein promoter. hCAST overexpression significantly reduced protease activity confirmed by reductions in acute calpain-mediated substrate proteolysis in the cortex and hippocampus following controlled cortical impact brain injury. Aspects of posttraumatic motor and cognitive behavioral deficits were also lessened in hCAST transgenic mice compared to their wildtype littermates. However, volumetric analyses of neocortical contusion revealed no histological neuroprotection at either acute or long-term time points in either transgenic line. Partial hippocampal neuroprotection observed at a moderate injury severity in neuron-specific calpastatin overexpressing transgenic mice was lost after severe TBI. Greater levels of calpastatin under the prion protein promoter line failed to protect against hippocampal cell loss after severe brain injury. This study underscores the effectiveness of calpastatin overexpression in reducing calpain-mediated proteolysis and behavioral impairment after TBI, supporting the therapeutic potential for calpain inhibition. However, the reduction in proteolysis without accompanied neocortical neuroprotection suggests the involvement of other factors that are critical for neuronal survival after contusion brain injury. Augmenting calpastatin levels may be an effective method for calpain inhibition and may have efficacy in reducing behavioral morbidity after TBI and neurodegenerative disorders.

This study looked in detail at the parental experience of having a child sustain traumatic brain injury (TBI); beginning with the child sustaining the injury, through the acute and chronic stages of rehabilitation, to the child’s return home. Mother and father dyads were interviewed in their own homes using a semi-structured interview schedule. A narrative analysis highlighted important findings through the identification and construction of several plots and subplots within parent narratives. These include that parents themselves appear to undergo trauma as a consequence of their child sustaining TBI; that parents made - and wanted to make - a major contribution throughout their child’s rehabilitation, and that all parents went - and are continuing to go - through a number of transitions in this process. Given that fathers have historically been neglected from research into child health issues, the finding here that mothers and fathers made a substantial contribution throughout the rehabilitation process is timely and important. For most parents, this event led to profound and long-lasting changes in their lives and life stories where their previous, hitherto narratives were ‘shattered’. On the child’s return home, these changes appear neither recognised nor supported by services. There seemed little if anything in service provision and coordination to meet the needs of children and parents, which resulted in parents continually fighting for services. Clinical implications are discussed as well as directions for future research.

Background: For Diffusion Tensor Imaging (DTI) to become a clinically useful tool in the detection of traumatic brain injury (TBI) and prediction of functional outcome, a reliable method enabling the identification of likely injury in individual patients needs to be developed. Objective: To explore different methods of analysing DTI measures to determine if individual TBI patients can be differentiated from a group of non-brain injured controls and if so, how these differences are associated with cognitive function. Method: 4 participants with TBI and 11 control participants were scanned using DTI and completed a battery of neuropsychological tests. The DTI measures of Fractional Anisotropy (FA) and Mean Diffusivity (MD) in the uncinate fasciculus were compared across individual TBI patients and a control group using 3 different methods of analysis. Results: The comparison of mean FA/MD from individual TBI patients with the overall mean FA/MD of the control group revealed that some TBI patients had lower values of FA whilst others had increased MD. This difference in FA may be associated with deficits in measures of attention. The histogram curves and cumulative frequency plots for individual TBI patients and the controls revealed subtle yet potentially significant differences in the distribution of FA/MD. However at this stage these differences could not be associated with cognitive function. Conclusion: Initial findings indicate that individual TBI patients can be differentiated from a control group using different methods with differing degrees of sensitivity. These differences may be related to cognitive function but further research is warranted before firm conclusions can be drawn.

Intrusive images are a common phenomenon in post-traumatic stress disorder (PTSD; American Psychological Society, 2013). Imagery-Rescripting (ImRs; Arntz & Weertman, 1999) is an experiential technique for targeting intrusive images and is gaining popularity as a treatment for PTSD (Arntz, 2012). Although there is evidence to suggest that ImRs is an effective treatment of PTSD (see Arntz, 2012), it is currently unclear how ImRs works. The aims of the present study were 1) to develop a coding scheme that captured important factors of ImRs session, and 2) to apply this coding scheme prospectively to investigate how certain factors might relate to treatment outcome. The study used thematic analysis (Braun & Clarke, 2006) to develop an ImRs coding scheme. Next, a single case experimental design was employed to track six participants over the course of their ImRs therapy for PTSD. Session content captured by the coding scheme was compared to changes in weekly outcome measures to investigate whether the presence of certain codes related to a reduction in PTSD symptoms. Results suggested a number of factors might be important for determining treatment outcome. Specifically, Attitude towards ImRs, Activation of the image, Ability to follow ImRs, Activation of original internal processes and internal processes during the re-script, Believability and Attitude towards the outcome are suggested as potentially important factors for determining ImRs efficacy. Study strengths, limitations and clinical implications are discussed. Recommendations for future research, including in-depth investigation of individual factors are suggested.

Background Traumatic brain injury (TBI) is a complex disease with a spectrum of symptoms and disabilities. Over the past decade TBI has become the focus of research due to growing epidemiological and clinical evidences that TBI incidences are strong risk factors for Alzheimer’s disease (AD). Major pathological hallmarks of AD are massive accumulations of amyloid-β peptide (Aβ) toxic oligomers and plaques. Neuroinflammation is also considered as a common denominator in AD and aging. The epidemiological and experimental studies have supported that non-steroidal anti-inflammatory drugs markedly reduce the age-related prevalence of AD and can slow amyloid deposition by mechanisms that still remain elusive. S100A9 is a multifunctional cytokine with diverse roles in the cell signaling pathways associated with inflammation and cancers. A widespread expression of S100A9 was also reported in many other ailments involving inflammatory processes, such as AD, malaria, cerebral ischemia and TBI, implying that S100A9 may be a universal biomarker of inflammation. The distinctive feature of S100A9 compared to other pro-inflammatory cytokines is its ability to self-assemble into amyloids, which may lead to the loss of its signaling functions and acquired amyloid cytotoxicity, exceeding that of Aβ. Methods S100A9 properties was studied under various ex vivo and in vitro conditions. First, human and mouse tissues with TBI and AD were subjected to microscopic, immunohistochemical and immunofluorescent techniques. Then, aged mouse treated with native, oligomeric and fibrillary S100A9 was also studied by using behavioral and neurochemical analysis. Moreover, S100A9 was established as a biomarker of dementia progression and compared with others such as Aβ42 and tau proteins, by studying cerebrospinal fluid (CSF) samples from different stages of dementia. Finally, in vitro experiments on S100A9 amyloidogenesis, co-aggregation with Aβ40 and Aβ42, digestion and cytotoxicity were also performed by using spectroscopic, atomic force microscopy and cell biology methods. Results S100A9-driven amyloid-neuroinflammatory cascade serves as a link between TBI and AD. We have found that S100A9 contributes to the plaque formation and intraneuronal responses in AD, being a part of the amyloid-neuroinflammatory cascade. In TBI we have found that extensive S100A9 neuronal production and amyloid self-assembly is triggered immediately after injury, leading to apoptotic pathways and neuronal loss. S100A9 is an integral component of both TBI precursor-plaques, formed prior to Aβ deposition, and AD plaques, characterized by different degree of amyloid maturation, indicating that all plaques are associated with inflammation. Both intra- and extracellular amyloid-neuroinflammatory cascades are intertwined and showed similar tendencies in human and mouse tissues in TBI and AD. Ex vivo findings are further supported by in vitro experiments on S100A9 amyloidogenesis, digestion and cytotoxicity. Importantly, being highly amyloidogenic itself, S100A9 can trigger and aggravate Aβ amyloid self-assembly and significantly contribute to amyloid cytotoxicity. Moreover, the CSF dynamics of S100A9 levels matches very closely the content of Aβ42 in AD, vascular dementia and mild cognitive impairment due to AD, emphasizing the involvement of S100A9 together with Aβ in the amyloid-neuroinflammatory cascade in these ailments. Conclusions The conclusions of this thesis is that the inflammatory pathways and S100A9 specifically represent a potential target for the therapeutic interventions during various post-TBI stages and far prior AD development to halt and reverse these damaging processes. / Role of pro-inflammatory S100A9 protein in amyloid-neuroinflammatory cascade in Alzheimer’s disease and traumatic brain injury