Thesis (Ph. D.)--University of New South Wales, 2006. / "May 2006." Title taken from title screen (viewed October 25, 2007). Includes bibliographical references (p. 188-206) and appendices.

Thesis (Ph. D.)--Dept. of Psychology. University of Missouri--Kansas City, 2006. / "A dissertation in psychology." Advisor: Lisa Terre. Typescript. Vita. Title from "catalog record" of the print edition Description based on contents viewed Oct. 30, 2007. Includes bibliographical references (leaves 140-158 ). Online version of the print edition.

It has been postulated that there could be a connection between traumatic brain injury (TBI) and motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS). As chronic traumatic encephalopathy (CTE) is caused by repeated TBI and is a newly examined disease, there has been little evaluation of the potential relationship between CTE and ALS. It was proposed that CTE is a risk factor for not only MND, but also ALS. There is significant evidence that even a single TBI is a risk factor for Parkinson's disease (PD), thought to be invoked by the inflammatory process that the brain undergoes following a TBI. General rigorous physical activity with trauma to the trunk or extremities does not appear to be a risk factor for ALS. However, physical activity with associated head traumas, especially repeated head traumas, does seem to increase the likelihood of developing ALS. The biological mechanism for this is suspected to be increase in free radicals during exercise in individuals who are predisposed to decreased antioxidant function. Additionally, individuals who have suffered repeated head trauma, even amongst the general population in a non-athletic setting, has been shown to drastically increase the individual's chance of developing ALS. CTE, which is most common in athletes, is speculated to be caused by TAR DNA-binding protein 43 (TDP-43), tau neurofibrillary tangle (NFT), and beta-amyloid (A-Beta) protein inclusions in brain tissue following a multitude of TBI during high level sport activity. There are individuals who suffer initially CTE, followed by ALS, indicating CTE is clearly a risk factor for ALS. Anatomically, the TDP-43, NTF, and A-Beta; inclusions are present in the brain tissue of both individuals with CTE alone as well as the individuals with CTE and ALS. The anatomic difference between these two pathologies is the inclusion of these three proteins in the spinal cord of ALS patients as well. Unfortunately, there are indications that previous studies of professional athletes and their development of ALS have presented with significant issues including confounding factors of the subpopulation and sample sizing. Additionally, the anatomical cause of TBI leading to ALS is still unknown. Further evaluation on the relationship between head injury and ALS must be dedicated to investigating the mechanism involved in developed PD versus ALS following TBI. The biologic sequence following TBI that leads to ALS must be examined and compared to individuals whom develop ALS but did not suffer TBI. Moreover, an assessment must be made to determine what causes some individuals to develop protein inclusions solely in the brain tissue, leading to CTE, and some individuals to have an advancement of the protein inclusions into the spinal cord, leading additionally to CTE followed by ALS.

Chronic Traumatic Encephalopathy (CTE) has been linked to contact sports, most notably boxing and American football, due to their propensity for repetitive head impacts. Concerns in the community for the safety of athletes in all contact sports has driven a significant amount of research into concussions, their long term effects, and strategies for treatment and prevention. Knowledge of long term brain health in response to neurotrauma is limited, a gap especially noticeable in the literature on non-catastrophic brain injuries sustained as a child. Concussion is a common injury that is often self-resolving with no lasting neurologic or cognitive deficits. Although repetitive brain trauma is hypothesized to be necessary and sufficient to lead to CTE, no human or animal models have definitively demonstrated the pathophysiologic connection or confirmed the mechanism of symptoms. The research to date has been case based, lacking prospective cohorts, with data complicated by convenience sampling. These factors limit the generalizability of conclusions. CTE is neuropathologically defined with variable symptoms; however, it is only diagnosable at postmortem autopsy making the etiology and prevalence difficult to understand. As more research is published to understand if there is an association between a neurocognitive degenerative disease and contact sports, the concentration is on professional athletes. Yet professional athletes do not represent the overwhelming majority of all contact sport participants. The proposed study will compare adults who participated in youth football, but not beyond the high school level, to a control group of adults who did not play contact sports. Evaluating their cognitive function with an online assessment, the Behavior Rating Inventory of Executive Function – Adult Version (BRIEF-A), data will be analyzed for signs of clinical cognitive impairment. The objective is to measure adults who represent the high percentage of youth football players who do not continue to the advanced levels. Data obtained from this study will help communities make informed decisions, and create the foundation for future studies on long term benefits and risks of contact sports for children.

abstract: Development of post-traumatic epilepsy (PTE) after traumatic brain injury (TBI) is a major health concern (5% - 50% of TBI cases). A significant problem in TBI management is the inability to predict which patients will develop PTE. Such prediction, followed by timely treatment, could be highly beneficial to TBI patients. Six male Sprague-Dawley rats were subjected to a controlled cortical impact (CCI). A 6mm piston was pneumatically driven 3mm into the right parietal cortex with velocity of 5.5m/s. The rats were subsequently implanted with 6 intracranial electroencephalographic (EEG) electrodes. Long-term (14-week) continuous EEG recordings were conducted. Using linear (coherence) and non-linear (Lyapunov exponents) measures of EEG dynamics in conjunction with measures of network connectivity, we studied the evolution over time of the functional connectivity between brain sites in order to identify early precursors of development of epilepsy. Four of the six TBI rats developed PTE 6 to 10 weeks after the initial insult to the brain. Analysis of the continuous EEG from these rats showed a gradual increase of the connectivity between critical brain sites in terms of their EEG dynamics, starting at least 2 weeks prior to their first spontaneous seizure. In contrast, for the rats that did not develop epilepsy, connectivity levels did not change, or decreased during the whole course of the experiment across pairs of brain sites. Consistent behavior of functional connectivity changes between brain sites and the "focus" (site of impact) over time was demonstrated for coherence in three out of the four epileptic and in both non-epileptic rats, while for STLmax in all four epileptic and in both non-epileptic rats. This study provided us with the opportunity to quantitatively investigate several aspects of epileptogenesis following traumatic brain injury. Our results strongly support a network pathology that worsens with time. It is conceivable that the observed changes in spatiotemporal dynamics after an initial brain insult, and long before the development of epilepsy, could constitute a basis for predictors of epileptogenesis in TBI patients. / Dissertation/Thesis / M.S. Bioengineering 2012

This work documents the treatment of a 20-year-old male suffering from Post Traumatic Stress Disorder as a result of his experience during two years of national service as an Operations "Ops" Medic in the South African Defence Force. The literature review is drawn largely from the body of work emerging from the Vietnam War, and in particular the work of Robert Lifton and Erwin Parson is considered. The case study consists of a detailed synopsis of the treatment based upon material from the therapy sessions. This section hopes to accurately convey the experience of working with someone suffering from Post Traumatic Stress Disorder and provide insight into the dynamics of such a therapeutic relationship. Finally the discussion examines the links between the theory and the treatment and attempts to understand the various factors which shaped and influenced the final outcome of the therapy. Special consideration is given to showing how essentially cognitive restructuring techniques are successfully utilised within a more existential, psychodynamic framework. Furthermore, there is a paucity of literature on the subject of combat-related Post Traumatic Stress Disorder in South Africa and it is hoped that this work will both point to a need for further research in this field whilst simultaneously provide guidance for those who wish to become involved in working with individuals suffering from Post Traumatic Stress Disorder.

Traumatic incidences happen all around the globe. Some of the people who experience trauma develop post-traumatic stress disorder (PTSD), while some do not. Even more interesting is that some also experience growth afterwards (post-traumatic growth; PTG). The purpose of this paper is to look at neural aspects of why some people develop PTSD and others PTG after a traumatic event. To fulfill the aim, both PTSD and PTG will be reviewed to create an image of the existing research in behavioral and neurological terms. In addition to looking at the constructs separately, a chapter will also look at studies where both PTSD and PTG are acknowledged collaterally in participants. When looking deeper into the theories of PTSD divisions occur, and more research is needed to establish the most prominent explanation of PTSD. PTG on the other hand has only been studied for a short period of time but yields important insights into trauma-related outcomes. These fields need to be submerged and new multidisciplinary definitions are needed for future research. The key to PTSD is suggested to emerge within the new field.

Mild Traumatic Brain Injuries (mTBIs) are non-penetrating brain injuries that do not result in gross pathological lesions, yet they may cause a spectrum of cognitive and behavioral deficits. mTBI has been placed in the spotlight because of increased awareness of blast induced and sports-related concussions, but the underlying pathophysiological mechanisms are poorly understood. Several studies have implicated neuronal membrane poration and ion channel dysfunction as the primary mechanism of injury. We hypothesized that injury forces utilize mechanically-sensitive, transmembrane integrin proteins, which are coupled to the neuronal cytoskeleton (CSK) and distribute injury forces within the intracellular space, disrupting CSK organization and reducing intercellular neuronal functionality. To test this, magnetic beads were coated with adhesive protein, allowing them to bind to integrins in the neuronal membrane in vitro. To apply forces to the neurons via the bound beads, we built custom magnetic tweezers and demonstrated that focal adhesions (FACs) formed at the site of bead binding. We showed that the beads were coupled to the CSK via integrins by measuring the disparate adhesion of the soma and neurite to their underlying substrate. The soma also required more force to detach than neurites, correlating with the FAC density between each neuronal microcompartment and substrate. We then utilized the magnetic tweezers to test whether beads bound to integrins injured neurons more than beads that bound to neurons nonspecifically. Integrin-bound beads injured neurons more often and the injury was characterized by the formation of focal swellings along axons, reminiscent of Diffuse Axonal Injury. While integrin-bound beads initiated swellings throughout neurons, beads bound nonspecifically only caused local injury where beads were attached to neurons. To demonstrate the electrical dysfunction of integrin-mediated injury forces, we adapted Magnetic Twisting Cytometry to simultaneously apply injury forces to beads bound to multiple cells within neuronal networks in vitro. The formation of focal swellings resulted in reduced axonal electrical activity and decreased coordinated network activity. These data demonstrate that the mechanical insult associated with mTBI is propagated into neurons via integrins, initiating maladaptive CSK remodeling that is linked to impaired electrical function, providing novel insight into the underlying mechanisms of mTBI. / Engineering and Applied Sciences

Traumatic Brain Injury (TBI) is linked to a diverse range of diffuse pathological damage for which there is a severe lack of therapeutic options. A major limitation to drug development is the inability to identify causal mechanisms that link head trauma to the multitude of secondary injury cascades that underlie neuropathology. To elucidate these relationships, it is important to consider how physical forces are transmitted through the brain across multiple spatial scales ranging from the whole head to the sub-cellular level. In doing so, the mechanical behavior of the brain is typically characterized solely by its material properties and biological structure. Alternatively, forces transmitted through distinct cellular and extracellular structures have been shown to influence physiological processes in multiple cell types through the transduction of mechanical forces into cellular chemical responses. As an essential component of various biological processes, these mechanotransduction events are regulated by mechanical cues directed through extracellular matrix (ECM) and cell adhesion molecules (CAM) to mechanosensitive intra-cellular structures such as focal adhesions (FAs). Using a series of in vitro models, we have implicated FAs in the cellular mechanism of traumatic axonal injury by showing that forces directed through these structures potentiate injury levels and, moreover, that inhibition of FA-mediated signaling pathways may be neuroprotective. In addition, we show that localizing trauma forces through specific brain ECM results in differential injury rates, further implicating mechanosensitive cell-ECM linkages in the mechanism of TBI. Therefore, we show that FAs play a major role in axonal injury at low strain magnitudes indicating that cellular mechanotransduction may be an important mechanism underlying the initiation of cell and sub-cellular injuries ultimately responsible for the diffuse pathological damage and clinical symptoms observed in diffuse axonal injury. Furthermore, since these mechanisms may present the earliest events in the complex sequelae associated with TBI, they also represent potential therapeutic opportunities. / Engineering and Applied Sciences

Focal damage to cartilage sustained in serious joint injuries typically goes unrepaired and may progress to post-traumatic osteoarthritis. However, in a bovine explant model we found that cartilage damage provoked the emergence of highly migratory cells that homed to the site of injury and appeared to re-populate dead zones. We hypothesized that the migrating population were chondrogenic progenitor cells engaged in cartilage repair. The surfaces of bovine osteochondral explants injured by blunt impact were serially imaged to follow cell migration. Migrating cells harvested from cartilage surfaces were tested for clonogenic, side population, chemotactic activities and multipotency in in vitro assays. Gene expression in migrating cells was evaluated by microarray and their potential for spontaneous cartilage regeneration was assessed in a chondral defect model. Migrating cells emerged from superficial zone cartilage and efficiently repopulated areas where chondrocyte death had occurred. In confocal examination with high magnification, we could clearly observe the morphology of elongated progenitor cells which were migrating toward cartilage defect area and these cells were distinguishable from round chondrocytes. The cells were also activated to migrate in cartilage defect model. Most migrated cells in fibrin were morphologically elongated and a few cells were differentiating to chondrocyte-like cells with the deposit of proteoglycans. These cells proved to be highly clonogenic and capable of chondrogenesis and osteogenesis, but not adipogenesis. They were more active in chemotaxis assays than chondrocytes, showed a significantly larger side population, and over-expressed progenitor cell markers and genes involved in migration, chemotaxis, and proliferation. To active migration of chondrogenic progenitor cells (CPCs) short-term enzymatic method was used around edge of cartilage defect. Surprisingly, CPCs migrated into fibrin defect and were differentiating into chondrocytes with abundant deposit of proteoglycans. This result strongly supports that progenitor cells are activated in traumatic cartilage injury and have great potential for cartilage repair. In conclusion, migrating cells on injured explant surfaces are chondrogenic progenitors from the superficial zone that were activated by cartilage damage to attempt repair. Facilitating this endogenous process could allow repair of focal defects that would otherwise progress to post-traumatic osteoarthritis.