A novel cell culture system was designed to serve as a model of neuroinflammation. Neurons, astrocytes, and microglia derived from embryonic and perinatal rat cortical tissue were combined in a three-dimensional hydrogel utilizing a method that facilitated cell maturation and viability. Chemical challenge of the cultures with a broad pro-inflammatory stimulus resulted in the production of inflammatory cytokines and other associated molecules commensurate with the response observed in vivo and in other in vitro systems. It was hypothesized that mechanical deformation of the multitypic neural cell cultures would produce a similar response and thus validate the system as an in vitro model of traumatic brain injury-induced neuroinflammation. Mechanical injury delivered using custom-manufactured culture chambers and injury devices successfully imparted a moderate level of cell death to the cultures. It was determined that a mechanically-induced inflammatory response required chemical stimulation prior to the injury. The research presented here describes the generation and characterization of a novel in vitro culture system and its implementation in experiments designed to model secondary injury mechanisms associated with injury-induced neuroinflammation. The findings of these studies, applications of the culture system, and future research avenues are discussed.

BACKGROUND/AIMS: Inconsistency in the use of secondary brain injury prevention guidelines among US trauma centers after severe traumatic brain injury is prevalent in many literature sources. However, this phenomenon has not been thoroughly studied. The purpose of this DNP project is to identify the key barriers and challenges in compliance to the evidence-based guidelines for secondary brain injury prevention. DESIGN: An exploratory, emergent design was used to collect descriptive qualitative data through the use of a survey. SETTING: Six Phoenix Metropolitan Level 1 trauma centers. PARTICIPANTS: All survey participants who consented to survey completion, which had greater than six months of experience and directly worked with patients suffering from a severe TBI in the clinical setting. MEASUREMENTS: Participant demographics (work experience, area of work, job title), current awareness and use of Brain Trauma Foundation guidelines, and time duration for evidence based order set implementation. Narrative responses were also used to identify barriers to current use of the BTF guidelines and factors that may promote their use in the future. RESULTS: A total of 43 participants consented to the survey study, with completion by 35 participants. RNs (n=27), Physicians (n=2), NPs or PAs (n=5), with an average work experience of 6 to 14 years (42.86%). A total of n=22 (62%) of participants were unaware of the current BTF guidelines for severe TBI and only 25% (n=9) aware that their facility has a protocol based on the BTF guidelines for severe TBI, while 51% (n=18) were unsure if their facility had a protocol. Barriers were identified in narrative form and were consistent with awareness/education, provider congruence, communication, and order set/protocol process improvement. CONCLUSION: The understanding of current patient management for severe TBI based on the BTF guidelines is sporadic among the greater Phoenix area Level 1 trauma centers. Requiring proof of BTF guidelines compliance by the ACS at time of Level 1 certification may increase the consistent recommended use of the BTF guidelines for the care of severe TBIs.

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The purpose of this study is to provide an inclusive portrait of the experience of female spouses living with traumatized male Canadian soldiers healing from Post-Traumatic Stress Disorder (PTSD). By facilitating the articulation of the spouses' stories this research gives a voice to and fosters appreciation for this neglected population. As well, this study helps clarify the needs and possible therapeutic interventions for spouses of soldiers in psychotherapy for PTSD. Although recently there has been an increased focus on addressing PTSD in soldiers, there has been comparatively little research and clinical attention given to the soldiers' families. For this study, in-depth interviews were conducted with six spouses of former peacekeeping Canadian soldiers who received group therapy for PTSD. Using the Life Story interview method, a spontaneous picture of the spouses' experiences was elicited as part of a comprehensive relationship narrative. This provided the opportunity for understanding the experience of living with a soldier in treatment for PTSD within a couple relationship and larger social context. Narrative summaries were created from the interviews and follow-up was conducted with each participant to gain feedback on these narratives. Participants were also given the opportunity to read each other's narratives and discuss their impressions. The narrative summaries are presented along with thematic results. The participants' stories revealed instances of aggression, primary trauma and problems related to their husbands' periods of alcohol abuse, so Figley's model of Secondary Traumatic Stress was not the best conceptual fit to explain the experiences of these women. Limited support was found, however, for Hobfoll's (1998)model of a loss spiral to help describe the descent into chronic disability associated with combat-related PTSD as well as the difficulties soldiers experience in their transition from military service. This study's implications for practice include recommendations for groups for military spouses; the need to address the iatrogenic suffering of soldiers and their spouses; treatment recommendations for soldiers with PTSD. Future research also needs to include delivery and evaluation of a group-based counselling intervention for the spouses of traumatized soldiers.

The scientific problem of the study Brain concussion is the most common subtype of the post-concussion syndrome in childhood. This is a mild traumatic brain injury that accounts for 80-90℅ of all cases. Individuals who have sustained brain concussion, i.e. mild traumatic brain injury, frequently complain of various symptoms that are commonly defined as the post-concussion syndrome. Such symptoms are headache, dizziness, nausea, attention disorders, memory problems, sleep disturbances, learning problems, fatigue, emotional instability, mood changes, anxiety, fear, etc. – all of these are defined in the International Classification of Diseases. The symptoms of the post-concussion syndrome are non-specific and subjective. Some patients indicate similar symptoms even without having experienced head injury; these symptoms can occur in the presence of other health disorders, such as the fatigue syndrome, neurasthenia, hyperactivity and attention disorders, as well as in cases of anxiety, mood and emotional disorders, and depression. During the last 25 years, over 500 articles on mild traumatic brain injury have been published in psychological literature, and a similar number of publications in medical literature. The results of scientific studies are quite different, and the variety of the results is still inciting heated scientific debates. Some researchers insist that brain concussion has long-tern sequelae. On the other hand, an opinion has emerged that even if... [to full text]

This thesis examines the associations between substance use/ misuse and mental health outcomes among Canadians with a Traumatic Brain injury (TBI). Its primary aim is to explore whether or not individuals with a TBI have higher rates of substance use/misuse and poorer mental health than Canadians without a TBI, and to examine two competing hypothesis that help to explain these behaviours -- the impaired brain functioning and the general coping hypotheses. Drawing on data from the 2009-2010 Canadian Community Health Survey, a nationally representative cross-sectional survey, this research assessed substance use and mental health outcomes among those with a TBI, as well as two control groups: (1) individuals with a back or spinal injury; and (2) healthy non-injured controls. Analyses include descriptive statistics and multivariate regressions (logistic and multinomial) adjusting for a range of injury and socioeconomic variables. Those with a TBI demonstrated significantly elevated rates of binge drinking, illicit drug use, and having an anxiety disorder relative to non-injured Canadians, and provided partial support for both the impaired brain functioning and general coping hypotheses to substance use. These findings indicate that public health policy should increase awareness amongst healthcare and social workers on the necessity of continued follow-up of those who experience a TBI in order to reduce future health conditions and to reduce the likelihood of re-injury.

Objective: The purpose of this study was to investigate the impact of salience on the comprehension of predictive inferences in adults with traumatic brain injury (TBI), by increasing the visual salience of the predictive sentence. This study also investigated whether a relationship existed between performance on a predictive inferencing comprehension task and working memory for this population. Increasing the salience of a crucial sentence in the predictive inferencing task may lead to better memory for the inferred information within the focused portion of the text (Gernsbacher & Jescheniak, 1995; Parkhurst, Law, & Niebur, 2002). Method: Six participants with TBI and six non-brain injured peers (NBI) took part in the study. Each participant was administered an inference comprehension task which consisted of a series of 55 stories. Each story incorporated one of five conditions: 1) a Recent salient condition (inferred information immediately preceded the comprehension question and was visually salient); 2) a Recent non-salient condition (inferred information immediately preceded the comprehension question but was not visually salient); 3) a Distant salient condition (inferred information occurred early in the story and was visually salient); 4) a Distant non-salient condition (inferred information occurred early in the story and was not visually salient); and 5) a Control condition (no inferred information in the story). In addition there were 20 filler stories. The predictive sentence was bolded in half the stories in order to increase the visual salience of the stimuli. In addition, a measure of working memory span (Lehman-Blake & Tompkins, 2001) was administered. Results: A significant main effect was found for Group, F(1,11) = 7.6, p= 0.019, with adults with TBI performing more poorly than matched controls. A significant main effect was also found for Condition, F(3,33) = 3.159, p = 0.038, with all participants performing more poorly in the Distant non-salient condition. No statistically significant interaction between Group x Condition was observed, F(3,33) = 0.469, p =0.706. Post-hoc comparisons revealed that all participants performed more poorly in the non-salient condition when the storage load was high (distant non-salient condition). Significant correlations were found for working memory span and the Distant salient condition (r =0.677, p < 0.05) and Distant non-salient condition (r = 0.646, p < 0.05). Conclusion: The results have both theoretical and clinical implications. Theoretically, the role of attention in working memory is of interest in language comprehension (e.g. Montgomery, Evans, & Gillam, 2009). This study may further contribute to studies of allocation of attention using increased salience to enhance comprehension. Clinically, the use of enhancing the salience of key information is a practical strategy that can be employed.

Fatal earthquakes such as that which occurred in Christchurch on February 22nd 2011, can result in survivors having difficulties with cognitively processing the event, which may be the precursor to posttraumatic stress symptoms. Trauma related dissociation has been proposed to be a mechanism related to these cognitive processing difficulties. Most research focusing on information processing and dissociation post-trauma has conducted controlled analogue studies or has not focused solely on information processing and dissociation. There is also scant research on these constructs across therapy. In response to this gap in research, two studies were developed. An association was proposed between dissociation and information processing as demonstrated by an increase in conceptual processing and a reduction in dissociation. It was predicted that an improvement in these constructs would be related to a reduction in PTSD symptoms over therapy. Study1 applied a case-study design to 5 individuals who were attending therapy for post-traumatic stress disorder in response to the trauma they had experienced from the Christchurch earthquakes. Study 2 assessed information processing and dissociation (via self and observer report) in 20 individuals who had direct exposure to the effects of the earthquake. Earthquake information processing and dissociation were assessed as they were happening nearly two year’s post-quake using correlation analyses and hierarchical regressions. The hypotheses were partially confirmed, in that an increase in conceptual processing was not shown to be associated with a reduction in dissociation. However, an increase in conceptual processing was shown to be related to trauma symptom improvement particularly for re-experiencing symptoms. In addition, study 2 demonstrated a possible relationship between trait dissociation and arousal symptoms. These findings partially support the proposed role information processing and dissociation play in the recovery from PTSD. The findings suggest that trauma related difficulties should be assessed as early as possible to resolve issues related to a delay in symptom reporting.

Traumatic brain injury (TBI) is a prominent disease in developed countries, and age is an important factor in functional outcome. Although aged patients typically show diminished recovery compared to young patients, and have higher mortality and morbidity following TBI, the mechanism is not well understood. To date, there is no effective therapeutic for TBI. Previous studies indicate a secondary injury in TBI begins immediately after impact, and is likely the major contribution to delayed neuron dysfunction and loss. Studies also suggest mitochondrial dysfunction and increased free radical species (ROS) production following TBI may play a key role in the process. To evaluate oxidative damage following TBI, especially in aging, young (3 months), middle aged (12 months) and aged (22 months) Fisher-344 rats were subjected to a unilateral controlled cortical impact (CCI) injury, and tissue sparing, 4-hydroxynonenal (HNE) and acrolein levels, and antioxidant enzyme activities, and DNA oxidative damage were measured. In order to evaluate changes in mitochondria following TBI, mitochondrial protein levels were investigated using young adult animals. To evaluate a potential therapeutic for TBI, the effect of creatine on oxidative damage was evaluated. These studies show an age dependent increase of oxidative damage following TBI, demonstrated by increased levels of 4-HNE, acrolein and 8-hydroxyguanine. Middle aged and aged animals showed increased tissue loss compared to young animals 7 days post injury. Mitochondrial proteins involved in the respiratory chain, carrier proteins and channel proteins were significantly decreased 24 h post injury in ipsilateral cortex, but increased in both ipsilateral and contralateral hippocampus. To study potentially protective compounds in TBI, animals were fed with creatine two weeks before TBI and showed less oxidative damage and increased antioxidant capacity, which suggests creatine may be a potential drug for clinical treatment of TBI. The work described in this dissertation is the first to show increased oxidative damage and diminished antioxidant capacity in TBI in aging. The study of mitochondriafollowing TBI using quantitative proteomics is also the first time to show multiple mitochondrial proteins change following TBI. These data are also the first to show creatine can increase antioxidant defenses. These studies contribute to our understanding the mechanisms of secondary injury in TBI in aging.

The studies presented in this dissertation were conducted with the objective ofgaining greater understanding into the mechanisms of successful aging, the role ofmitochondria dysfunction in traumatic brain injury, and also on the mechanisms ofimproved learning and cognitive function in the aging.Aging is usually characterized by impairments in physiological functionsincreasing its susceptibility to dementia and neurodegenerative disorders. In thisdissertation, the mechanisms of dementia-free aging were investigated. The use of anantioxidant fortified diet and a program of behavioral enrichment in the canine model ofhuman aging was shown to result in a significant decrease in the levels of oxidativestress. A proteomic analysis of these brains also demonstrated a significant decrease inthe oxidative modification of key brain proteins and an increase in the expression levelsof other key brain proteins associated with energy metabolism and antioxidant systemswhich correlated with improved learning and memory.We show that following TBI key mitochondrial-related proteins undergoextensive oxidative modification, possibly contributing to the severe loss ofmitochondrial energetics and neuronal cell death previously observed in experimentalTBI.Taken together, these findings support the role of oxidative stress in thepathophysiology of aging and age-related neurodegenerative disorders and in CNS injury.These studies also show that antioxidants and a program of behavioral enrichmentprovide protection against oxidative stress-mediated cognitive impairments.