Traumatic brain injury (TBI) is a major cause of death and disability. TBI is frequently followed by cerebral ischemia which is a great contributor to secondary brain damage. The main causes of cerebral ischemia are pathophysiological changes in cerebral blood flow and metabolism. Treatment of TBI patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted treatment protocols. However, ICP and CPP alone do not provide information of the oxygen availability in the brain. Monitoring of brain tissue oxygenation (BtipO2) may give additional and valuable information about the risk for development of ischemia in TBI patients. The aims of this thesis were to study BtipO2 monitoring devices in-vitro regarding accuracy and stability, to detect threshold level of cerebral ischemia in-vivo and finally to examine the cerebral oxygen levels and cerebral metabolism in TBI patients. The BtipO2 probes performed with high accuracy and stability at different clinically relevant oxygen concentrations. A pig TBI model was developed by step-wise intracranial volume/pressure increase. Volume increase resulted in a gradual increased ICP, decreased CPP, intracranial compliance and BtipO2, respectively. Brain death (BD) was confirmed by negative CPP and negligible amount of previously injected microspheres in the brain tissue. The model simulated the clinical development of BD in humans with a classical pressure-volume response and systemic cardiovascular reactions. The model should be suitable for studies of brain injury mechanisms. From the same in-vivo model it was also possible to detect the threshold level of cerebral ischemia in the pig, where BtipO2 below 10 mmHg and CPP below 30 mmHg was associated with an impaired cerebral metabolism (microdialysis lactate to pyruvate ratio >30). BtipO2 together with cerebral microdialysis were studied in 23 severe TBI patients. We observed different patterns of changes in BtipO2 and cerebral microdialysis biomarkers in focal and diffuse TBI.  Increased cerebral microdialysis levels of glutamate, glycerol or the lactate/pyruvate ratio were observed at BtipO2 < 5 mmHg, indicating increased vulnerability of the brain at this critical level of tissue oxygenation in TBI patients.

Background: Spinal cord injury (SCI) is heterogeneous in nature and can be complicated by inflammation and scarring in the subarachnoid space (arachnoiditis). The constellation of traumatic injury and arachnoiditis can lead to extensive intraparenchymal cysts or post-traumatic syringomyelia (PTS), due to alterations in fluid flow and pressure dynamics in the subarachnoid space. Hypothesis: Intrathecal injection of a bioengineered hydrogel containing hyaluronan (HA) will improve functional recovery following severe spinal cord injury associated with arachnoiditis. Methods: Acute to subacute pathophysiological events were characterized in non-injured sham rats, rats receiving a clip compression/contusion injury (SCI), rats receiving an intrathecal kaolin injection (Arachnoiditis) and in rats receiving SCI plus kaolin injection (PTS). Next, a HA containing hydrogel (HAMC) or artificial cerbralspinal fluid (aCSF) control was injected into the subarachnoid space 24 hours following PTS injury. To assess treatment efficacy, subacute pathophysiology was assessed as was long-term neurobehavioural and neuroanatomical recovery. Finally, in vitro studies examined the effect of HA on TLR4 activation using lipopolysaccharide in primary rat microglial cultures. Results: PTS animals exhibited a greater parenchymal injury response as compared to the sum of SCI alone or arachnoiditis alone. Injection of HAMC reduced the extent of scarring and inflammation in the subarachnoid space and improved neurobehavioural and neuroanatomical recovery relative to aCSF controls. These improvements were associated with reduced chondroitin sulfate proteoglycan and IL-1α expression and a trend towards and axonal preservation. In vitro studies demonstrated that HA is capable of reducing TLR4 mediated inflammation in microglia. Conclusions: Acute arachnoiditis potentiates the intensity of intraparenchymal inflammatory and scarring events following SCI. When HAMC was injected intrathecally following PTS injury, it mitigated some of the pernicious effects of arachnoiditis. Part of the therapeutic action of HAMC can be attributed to the ability of HA to reduce TLR4 mediated inflammation in microglia, possibly through an extracellular mechanism.

Objective: To examine sleep and wake disorders following traumatic brain injury (TBI) and their impact on recovery of cognition, communication and mood. Research Design: This three-manuscript thesis comprises an introduction to sleep in the context of human function and development. It is followed by a systematic review of the literature pertaining to sleep and wake disorders following TBI, and then explores the relationship between sleep and arousal disturbance and functional recovery of cognitive-communication through a single case study, pre–post intervention. Finally, a larger study longitudinally explores the impact of treatment to optimize sleep and wakefulness on recovery of cognition, communication and mood through objective and subjective measures, pre-post intervention. The thesis concludes with a chapter that addresses the implications of findings for rehabilitation from the perspective of the International Classification of Functioning, Disability and Health (ICF), and a presentation of future research directions for the field Methods: The first manuscript involved a systematic review and rating of the quality of evidence. The second manuscript involved the evaluation of sleep and wakefulness by objective measures, and longitudinally by self-report through the Daily Cognitive-Communication and Sleep Profile (DCCASP, © Wiseman-Hakes 2008, see Appendix S). Cognitive-communication abilities were also measured by the DCCASP. The third manuscript utilized a single case series and cohort design to evaluate sleep and wakefulness, and to examine cognition, communication and mood at baseline and following optimization of sleep and wakefulness. Results: For Manuscript One, 43 articles were reviewed for levels and quality of evidence across 5 domains: epidemiology, pathophysiology, neuropsychological implications, intervention and paediatrics. In Manuscript Two, we showed that there was a statistically and functionally significant relationship between perceived quality of sleep and language processing, attention and memory, seen across the phases of the intervention. In Manuscript Three, we showed that there were statistically and functionally significant improvements across several domains of cognition, communication and mood in response to treatment. Conclusions: Sleep and wake disorders after TBI are pervasive, and can negatively impact rehabilitation and recovery. There is a need for systematic evaluation and intervention for these disorders in all persons with TBI.

In two separate studies, we used diffusion tensor imaging (DTI)to examine white matter changes secondary to traumatic brain injury (TBI) and spinal cord injury (SCI). The first study examined the utility of DTI for a single case diagnosis of mild TBI (mTBI) and demonstrated that the anterior limb of the internal capsule and the genu of the corpus callosum were sensitive and specific to mTBI. The second study examined the sub-acute effects of SCI on white matter tissue in the brain and demonstrated that SCI patients have a significantly greater degree of FA asymmetry than control subjects in the superior and posterior corona radiata. The first study has provided preliminary proof of principal evidence that DTI can be used to diagnose mTBI in individual cases. The second study suggests that the degree of asymmetry may be a useful biomarker for detecting subtle white matter changes.

In two separate studies, we used diffusion tensor imaging (DTI)to examine white matter changes secondary to traumatic brain injury (TBI) and spinal cord injury (SCI). The first study examined the utility of DTI for a single case diagnosis of mild TBI (mTBI) and demonstrated that the anterior limb of the internal capsule and the genu of the corpus callosum were sensitive and specific to mTBI. The second study examined the sub-acute effects of SCI on white matter tissue in the brain and demonstrated that SCI patients have a significantly greater degree of FA asymmetry than control subjects in the superior and posterior corona radiata. The first study has provided preliminary proof of principal evidence that DTI can be used to diagnose mTBI in individual cases. The second study suggests that the degree of asymmetry may be a useful biomarker for detecting subtle white matter changes.

Two of Don DeLillo’s recently published novels, The Body Artist (2001) and Falling Man (2007), feature performance artists performing trauma. Through the bodies of these performers, DeLillo restates the central concern of trauma studies: if trauma is that which denies mediation, how may we speak about traumatic experience? DeLillo’s stagings of traumatic (re)iterations illustrate how the missed originary moment of trauma precludes directly referential content in traumatic representation. But I propose that performed trauma – the knowledge of forgetting addressed to another – recapitulates the structure of traumatic experience itself, thereby revealing trauma to be wholly constituted in repetition, and providing a means of speaking about the unspeakable. I hope to illustrate how restoring trauma to language revives the ethical and political efficacy of traumatic representation.

Brain injury is a serious clinical problem. The success of recovery from brain injury involves functional compensation in the affected brain area. We are interested in general mechanisms that underlie compensatory plasticity after brain damage, particularly when multiple brain areas or multiple modalities are included. In this thesis, I studied the function of auditory cortex after recovery from neonatal midbrain damage as a model system that resembles patients with brain damage or sensory dysfunction. I addressed maladaptive changes of auditory cortex after invasion by ectopic visual inputs. I found that auditory cortex contained auditory, visual, and multisensory neurons after it recovered from neonatal midbrain damage (Mao et al. 2011). The distribution of these different neuronal responses did not show any clustering or segregation. As might be predicted from the fact that auditory neurons and visual neurons were intermingled throughout the entire auditory cortex, I found that residual auditory tuning and tonotopy in the rewired auditory cortex were compromised. Auditory tuning curves were broader and tonotopic maps were disrupted in the experimental animals. Because lateral inhibition is proposed to contribute to refinement of sensory maps and tuning of receptive fields, I tested whether loss of inhibition is responsible for the compromised auditory function in my experimental animals. I found an increase rather than a decrease of inhibition in the rewired auditory cortex, suggesting that broader tuning curves in the experimental animals are not caused by loss of lateral inhibition. These results suggest that compensatory plasticity can be maladaptive and thus impair the recovery of the original sensory cortical function. The reorganization of brain areas after recovery from brain damage may require stronger inhibition in order to process multiple sensory modalities simultaneously. These findings provide insight into compensatory plasticity after sensory dysfunction and brain damage and new information about the role of inhibition in cross-modal plasticity. This study can guide further research on design of therapeutic strategies to encourage adaptive changes and discourage maladaptive changes after brain damage, sensory/motor dysfunction, and deafferentation.

The main focus of this study was to investigate how Swedish military veterans experience that events during an international service affect them after completed mission. This also includes the contact with their relatives. Secondly, this study deals with the course of the crisis, personal defense mechanisms, cumulative stress and post-traumatic stress syndrome (PTSD). The study was performed using a qualitative method and comprises individual interviews with six Swedish veterans. The responders were all men of different military positions, who participated in one or more international missions during 1993 to 2011. The results of this study show that, according to the veterans, the return back home is the most strenuous part of an international mission. With all the new experiences that an international service brings fresh in their memories, it is hard to re-adjust to the life of a civilian. In connection with the return back home, different degrees of stress reactions were also commonly seen, for example sleep disturbance, restlessness and exhaustion. One of the veterans being interviewed was also affected by post-traumatic stress syndrome, although healthy again at the time of the study.

Personer som genomgått en traumatisk händelse befinner sig i riskzonen för att utveckla post-traumatic stress disorder (PTSD), som innebär en stor livsbegränsning och ett stort lidande. Dagligen möter hälso- och sjukvårdspersonal personer som ännu ej diagnostiserats och det är därför av vikt att kunna identifiera PTSD-symptom. Syftet med litteraturstudien var att undersöka samband mellan olika trauman och PTSD-symptom enligt diagnostiseringssystemet DSM IV. Studien grundades på en deduktiv ansats och resultatet bestod av 15 vetenskapliga artiklar som granskades. Resultatet behandlade DSM IV:s tre symptomkluster: re-experience/intrusion, avoidance och hyperarousal. Studien fann att det kan föreligga en skillnad mellan olika typer av trauma och vilka PTSD-symptom som var det mest frekvent upplevda. Det framkom också i studien att re-experience/intrusion och avoidance var de kluster som var mest frekventa hos dem som uppvisade PTSD-symptom efter ett trauma. Det finns ett behov av en utökad kvalitativ forskning inom området PTSD-symptom, samtidigt som hälso- och sjukvårdpersonal är i behov av att hålla sig uppdaterade när det kommer till de symptom som är ett resultat av sjukdomen. Det är av vikt att synliggöra PTSD och att låta kunskapen kring psykisk ohälsa få mer utrymme under sjuksköterskeutbildningen. För att tidigare kunna identifiera PTSD krävs en utförligare anamnes, där sjuksköterskan kan synliggöra tidigare upplevda trauman hos personen. Personer som hälso- och sjukvården vet har genomgått ett tidigare trauma kan vara i behov att screenas för PTSD.

En positiv eller negativ livsinställning, djur, natur, tro och utbildning, är det faktorer som har skyddande egenskaper? Personerna som fått behandling professionellt, har bearbetat händelserna de varit med om bättre än de som inte har fått hjälp med bearbetning. De personer som har en positiv livsinställning, i kombination med att de fått professionell hjälp av någon, har bearbetat de traumatiska händelser de varit med om bättre, än personer som har en negativ livsinställning, eller inte fått professionell hjälp. Några av personerna som intervjuats har även haft stor hjälp av att vistas ute i naturen tillsammans med sina hundar. Hundarna har varit ett stort stöd mentalt och en god vän som lyssnat när de mått dåligt. / A positive or negative approach to life, animals, nature, faith and education, are those factors with protective characteristics? Persons that have got professional treatment, have processed the experienced incidents, better than those who have not received help to process the incidents. Those who have a positive approach to life, combined with professional treatment, have processed traumatic experiences better than persons with a negative approach to life, or those with no professional treatment offered. Some of the interviewed persons have gained a lot by spending time with their dogs in nature. The dog has acted as mental support and a good friend, who has listened when the person has been depressed and in need of support.