Addressing the comprehensive needs of individuals with brain injuries is a growing concern in brain injury rehabilitation as well as evaluating the efficacy of these conventional therapeutic modalities: cognitive rehabilitation, and physical, occupational, and speech therapies. Therapeutic dance/movement has not been an integral part of these core services. I have observed its potential, however, during the past thirteen years while providing this intervention to individuals with brain injuries. The focus of this dissertation was to gain a better understanding of the dynamics of a therapeutic dance/movement intervention for individuals with brain injuries by comparing it to conventional physical therapy. Physical therapy, given its longevity in providing rehabilitative services to individuals with brain injuries, afforded a means by which to more systematically explore therapeutic dance/movement. Five individuals with brain injuries were observed and analyzed as they participated in five weekly therapeutic dance/movement sessions and five weekly physical therapy sessions. Laban Movement Analysis (LMA) was used as the observation and analytic tool for the purpose of elucidating similarities and differences between the two interventions in relation to the five case studies. Two questions guided the inquiry: (a) What are the similarities and differences between a physical therapy intervention and a dance/movement intervention? and (b) What are the dynamics of a therapeutic dance/movement intervention? Findings revealed that the physical therapy intervention focused specifically on body level connectivity and single joint action movement from a <i>Body</i> perspective. In comparison, the dance/movement intervention incorporated body level connectivity in addition to the dynamics of <i>Breath/Core Support</i> and <i>Grounding</i>, <i>Effort-Life</i>, <i>Spatial Intent</i>, and Aspects of <i>Shape</i>, providing the spectrum of <i>Body</i>, <i>Effort</i>, <i>Space</i>, and <i>Shape</i> ( <i>BESS</i>) components in harmony with the <i>Movement Themes: Whole/Part, Inner/Outer, Function/Expression, Exertion/Recuperation</i>, and <i>Mobility/Stability</i>.The dance/movement intervention imparted an integrative mind-body approach to learning about one's Inner and Outer self and one's ability to cope with and connect to one's environment. Knowledge was added to the current literature at an opportune time in the brain injury rehabilitation field. Rehabilitation professionals are recognizing the need to transform current assumptions regarding the essential aspects of brain injury rehabilitation and seek additional non-medical model approaches to rehabilitation. This study offers a therapeutic modality along with a viable measurement tool that has the potential for meeting this need. Recommendations for future research are offered. / Ph. D.

The purpose of this linear-analytic exploratory case study is to illustrate the reintegration process from acute care and rehabilitative care to the traditional school setting after one has sustained a Traumatic Brain Injury (TBI). TBI is an unrecognized educational challenge. Few educational professionals are aware of the divarication of TBI. Traumatic Brain Injury is the leading cause of death and disability in children and adolescents in the United States. The review of literature reveals there is a void between the requirements of the law and educator preparedness regarding TBI. There is a need for a proactive means to enhance transition and reintegration of a TBI student from rehabilitation to the traditional school setting. The research study showed the schematic efforts of one school division to integrate a TBI student. This exploratory case study emphasized the importance of a proactive education treatment planning process that facilitates the transition to the school setting. The study is qualitative in design and examined the sequence of subtopics of the problem, a review of relevant literature, methods used, findings of the data collected and analyzed, and conclusions and implications from the findings. This case study is analogous to a single experiment. Data were gathered from archival records, educational records, medical records, teachers and therapists comments, friends' perceptions, family histories, recollections, and interviews with participants in the reintegration process. There were three major domains that have been extracted from the case study. The first domain, the strengths and weakness of the student in the post traumatic brain injury environment were collated, collected, and analyzed. The second domain, the adaptation of Larry involved three general sub sets: (1) Larry's self adaptation, (2) the participants' roles in the student's adaptation, and (3) other influential factors in Larry's adaptation. The third domain centers on the strengths and weaknesses of the strategies used by the school division in the reintegration process. The strengths fell into five general categories; (1) caring professional (2) existing structure for disabled students, (3) cooperation, (4) willingness of general education teachers to make accommodations, and (5) willingness of school-based clinicians to try a variety of approaches. The weaknesses consisted of seven categories; (1) little knowledge of TBI, (2) no in-house pro-active plan,(3) no historical data on TBI, (4) no written records, (5) not central structure (scattered resources), (6) no written plan, and (7) no roster teacher/case manager with authority to direct staff with TBI scenario. The study will enhance the understanding of TBI and will provide a meaningful guide to parents, educators, and school based clinicians. The results illustrated that the data base of this study contained the critical pieces of evidence, this evidence was presented neutrally, and the evidence is valid. A holistic overview of the findings included the major domains and data sources that were explored. Additionally, the integrant building blocks that support this holistic overview are provided. In conclusion this case study discusses implications and recommendations. Of note is the reconciliation of this case study with the literature on TBI. / Ed. D.

Mild traumatic brain injury (mTBI) accounts for approximately 73-83% of all traumatic brain injuries (TBI) and continues to be a serious clinical challenge [1]. The role of injury mechanism in TBI has been widely debated, and it is believed that although there are differences between diffuse and focal TBI, the resulting injury is not influenced by the way in which it was acquired [1], [2]. It is known that TBIs can cause cognitive impairments that are often due to injury experienced in the hippocampus [2]. In response to insult, quiescent neural stem cell (NSC) populations within the dentate gyrus region of the hippocampus become activated. Stem cell differentiation following injury is hypothesized to be unique for diffuse and impact TBIs, primarily due to the differences in mechanotransduction pathways triggered by each respective injury. By quantifying the lineage of stem cells through immunohistochemistry, this study examined the dentate gyrus following mTBI in a rodent model, and the contribution that injury mechanism plays in mTBI outcomes. Additionally, the behavioral effects of mTBI were assessed through open field testing at 72 hours and four weeks following injury. Overall, these findings indicated that after four weeks following mTBI, there are not significant differences between impact and blast both from an immunohistochemical and behavioral standpoint. Despite there being few differences between injury groups, these findings help clarify the role of injury mechanism not only in the context of neurogenesis, but they also inform future studies addressing preventative and treatment strategies for mTBI. / Master of Science / Mild traumatic brain injury (mTBI) accounts for approximately 73-83% of all traumatic brain injuries (TBI) [1]. There are two main ways in which a mTBI can occur: through diffuse or focal injury. A diffuse injury is due to the brain experiencing a force that does not physically come into contact with the head, such as a shockwave from an explosion. These types of injuries typically affect the entire head. Impact injuries on the other hand, are caused by the head encountering an object at a force that causes injury to the brain. These injuries tend to be focal, as the entire head rarely comes into contact with an object. Both diffuse and focal injuries can cause mTBI, and there is a current debate questioning if the mode of injury has an impact on the damage experienced by the brain [1], [2]. However, it is also known that mTBI can cause cognitive impairments such as changes in behavior, memory, and even mental health, which can occur in the hippocampus of the brain [2]. Within the hippocampus, there is a small subset of cells referred to as neural stem cells (NSC) that become active following injury. The activation of these cells is believed to be in response to injury in the brain. Furthermore, NSCs have the ability to differentiate into various cell types within the brain, including astrocytes, oligodendrocytes, and neurons. Each of these cell types perform an integral role in the function of the brain. It is hypothesized that the response of NSCs in the hippocampus is unique depending on if an injury was acquired through diffuse or impact mechanisms. To investigate this, the lineage of NSCs was quantified within the hippocampus following blast and impact mTBI in a rodent model. Additionally, the behavioral effects of diffuse and impact injury were investigated at 72 hours and four weeks following injury. Despite there being no significant differences in outcomes between injury groups, these findings help clarify the role of injury mechanism not only in the context of NSC response, but they also inform future studies addressing preventative and treatment strategies for mTBI.

Millions of people sustain a mild traumatic brain injury (concussion) each year. While most clinical signs and symptoms resolve within 7-10 days for the majority of typical concussions, some gait and balance tasks have shown abnormalities lasting beyond the resolution of clinical symptoms. These abnormalities can persist after athletes have been medically cleared for competition, yet the implications of such changes are unclear. Most prior research has examined straight gait and standard measures of balance, yet there is a lack of knowledge regarding potential persistent effects on non-straight maneuvers or on indicators of motor control variability or complexity. To expand the knowledge of post-concussion locomotor and postural changes, this investigation examined the recovery of recently concussed athletes longitudinally, over the course of one year, in three domains: 1) path selection and body kinematics during turning gait, 2) non-linear local dynamic stability during straight gait, and 3) postural control complexity during quiet standing. Compared to matched health controls, concussed athletes exhibited significant and persistent differences in turning kinematics, local dynamic stability, and postural complexity over the initial six weeks following injury. These motor differences may increase the risk of injury to concussed athletes who are cleared to return to play. Given the persistent nature of these effects, future clinical tests may benefit from incorporating gait assessments before returning athletes to competition. Future research should prospectively and longitudinally monitor locomotor and postural control in conjunction with structural and functional changes within the brain to better understand the pathophysiology of concussions and potential rehabilitation strategies. / Ph. D.

Traumatic brain injury (TBI) continues to be a widespread problem in the United States with approximately 1.7 million occurrences annually [1]. Current automotive crash test standards use the Head Injury Criterion (HIC) [2] to assess head injury potential, but this metric does not relate an impact to underlying damage. For an injury metric to effectively predict TBI, it is crucial to relate level of impact to resulting injury. The research presented in this dissertation explains the development and repeatability of two novel injury devices, impact response characterization over the course of 24 hours in the Gottingen minipig and the relationships between metabolite changes, underlying disruption, and impact kinematics, and the characterization of impact response over the course of 72 hours. The translation-input and combined translation and rotation-input injury devices were shown to be repeatable, minimizing the number of animals needed for testing. Impact response over the course of 24 hours showed axonal disruption through immunostaining and proton magnetic resonance spectroscopy. The translation-input injury group metabolite analyses revealed the initial stages of glutamate excitotoxicity while the combined-input injury group showed a clear pathway for glutamate excitotoxicity. Numerous correlative relationships and potential underlying disruption predictors were found between metabolites, immunostaining, and kinematics. The most promising predictor combination for the translation-input injury device was N-acetylaspartylglutamate/Scyllo at 24 hours compared to 1 hour and linear speed for predicting underlying light neurofilament disruption. For the combined-input injury device, the strongest predictor combination was Glutamine/N-acetylaspartylglutamate at 24 hours compared to baseline and angular acceleration for predicting underlying light neurofilament disruption. Statistically significant predictors were found between Glutamate+Glutamine/Total Creatine at 24 hours compared to baseline and all kinematics and injury metrics with an angular component for predicting heavy neurofilament disruption. Analyses over the course of 72 hours revealed persistent axonal disruption and metabolite perturbations. Overall, this dissertation and the complementary parts of this project have many societal implications. Due to the high incidence of traumatic brain injury, there is a need for prevention, mitigation, and treatment strategies. Developing a new injury metric will help improve prevention strategies, especially in the automotive, sporting, and military environments. 1 Faul, M., Xu, L., Wald, M. M., and Coronado, V. G. (2010). Traumatic Brain Injury in the United States. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. 2 Versace, J. (1971). A Review of the Severity Index. SAE Technical Paper. No. 710881 / Ph. D.

Blast-induced traumatic brain injury (bTBI) remains a significant problem among military populations. When an explosion occurs, a high magnitude positive pressure rapidly propagates away from the detonation source. Upon contact, biological tissues throughout the body undergo deformation at high strain rates and then return to equilibrium following a brief negative pressure phase. This mechanical disruption of the tissue is known to cause oxidative stress and neuroinflammation in the brain, which can lead to neurodegeneration and consequently poor cognitive and behavioral outcomes. Further, these clinical outcomes, which can include chronic headaches, problems with balance, light and noise sensitivity, anxiety, and depression, may be sustained years following blast exposure and there are currently no effective treatments. Thus, there is a need to investigate the acute molecular responses following bTBI in order to motivate the development of effective therapeutic strategies and ultimately improve or prevent long-term patient outcomes. It is important to not only understand the acute molecular response, but how the brain tissue mechanics drive these metabolic changes. The objective of this work was to identify the interplay between the tissue-level biomechanics and the acute bTBI pathophysiology. In a rodent bTBI model, using adult rats, intracranial pressure was mapped throughout the brain during blast exposure where frequency contributions from skull flexure and wave dynamics were significantly altered between brain regions and were largely dependent on blast magnitude. These findings informed the subsequent spatial and temporal changes in neurometabolism. Amino acid molecular precursor concentrations decreased at four hours post-blast in the cortex and hippocampus regions. This motivates further investigation of amino acids as therapeutic targets aimed to reduce oxidative stress and prevent prolonged injury cascades. However, neurochemical changes were not consistent across blast magnitudes, which may be explained by the disparities in biomechanics at lower blast pressures. Lastly, we investigated the acute changes in metabolic regulators influencing excitotoxicity where it was found that astrocytes maintained normal clearance of excitatory and inhibitory neurotransmitters prior to astrocyte reactivity. Outcomes of this work provide improved understanding of blast mechanics and associated acute pathophysiology and inform future therapeutic and diagnostic approaches following bTBI. / Doctor of Philosophy / Blast-induced traumatic brain injury (bTBI) remains a significant problem among military populations. When an explosion occurs, a high magnitude positive pressure wave rapidly propagates away from the detonation source. Upon contact, biological tissues throughout the body undergo deformation that can cause injury. This mechanical disruption of the tissue is known to trigger negative biological processes that lead to persistent cognitive and behavioral deficits. Further, these clinical outcomes, which can include chronic headaches, problems with balance, light and noise sensitivity, anxiety, and depression, may be sustained years following blast exposure. There are currently no effective treatments that can help those afflicted, and biomarkers for injury diagnostics are limited. Thus, there is a great need to investigate the early biological responses following bTBI in order to motivate the development of effective therapeutic strategies and ultimately improve or prevent long-term patient outcomes. It is important to not only understand the immediate responses, but also how the brain tissue mechanics drive these metabolic changes. The objective of this work was to identify the interplay between the brain biomechanics and the acute bTBI pathophysiology. Using a translational animal model, pressure inside the brain was measured with pressure sensors during blast exposure. Subsequent spatial and temporal changes in neurochemical concentrations were quantified. The results showed (1) significant disparities in the pressure dynamics inside the brain and it varied across brain regions, (2) neurochemical precursors may have therapeutic potential post-injury, and (3) biomechanical and neurochemical responses were dependent on blast severity. Outcomes of this work provide improved understanding of blast mechanics and associated pathophysiology and inform future therapeutic and diagnostic approaches to prevent prolonged injury cascades.

While there has been ample research examining the relationship between an acute concussion on immediate neuropsychological performance, very little research has examined the relationship between lifetime concussion history with current neuropsychological performance. We collected preseason neuropsychological test performance (ImPACT) and a detailed lifetime concussion history questionnaire from 71 UCF football players. Stepwise linear regressions were conducted for each of the five ImPACT domain scores for the 18 participants that reported at least one lifetime concussion. The regressions used the following four concussion history predictors: total number of lifetime concussions, length of time between last concussion and lmPACT testing, severity of worst concussion, and severity of most recent concussion. Results revealed that only one ImpACT domain score had at least one predictor enter the model. For the domain of visual memory, the predictor of length of time between last concussion and ImPACT testing entered the model (and only that predictor),P = 4.07, t(l7) = 2.78,p = .01, R1 = .33, as a shorter length of time between the last concussion and the preseason testing related to lower performance on the visual memory tests. Many athletes and clinicians assume that the cognitive effects of a concussion are relatively brief in duration. However, the results of this study suggest that, at least for visual memory, these effects may last for several years following a concussion. The correlational design of this study precludes drawing conclusions about the causal direction of this relationship, but future longitudinal research may be able to clarify this important preliminary finding.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality among young children and adults. This primary injury initiates an inflammatory response that may lead to a secondary brain injury. Nursing care in the critical care setting supports prevention or reduction of secondary injury through control of intracranial pressure (ICP), mean arterial pressure (MAP), and the subsequent cerebral perfusion pressure (CPP). While secondary injury may be preventable, some nursing interventions may contribute to increased ICP and decreased CPP. Patients with increased ICP or decreased CPP are at risk for poor clinical outcomes. This literature review examined the effort of routine nursing care interventions on outcomes of TBI patients in the critical care setting. Eleven research articles studying head of bed elevation, head and neck positioning, turning, and spacing of patient care activities were the focus of the analysis. Results typically showed positive outcomes by elevating the head of the bed to thirty degrees. CPP was also maintained at thirty degrees, but showed varied results. ICP and CPP are best controlled with the head and neck in a neutral position. Turning patients is a routine nursing intervention that contributes to increased ICP in some positions in some patients. Most studies suggest ICP is lowest in the supine position and highest in the left lateral position, but differences in findings were noted. Providing basic nursing care interventions in close succession also may contribute to increases in ICP in some patients. Results from this review provide evidence to support the importance of assessing and planning care for each TBI patient individually. It is hoped that findings from this review will provide guidance for bedside nurses to improve clinical practice and drive future research to support best practices for care of patients who suffer TBI.

Traumatic brain injury (TBI) is a growing health concern worldwide that affects a broad range of the population. As TBI is the leading cause of disability and mortality in children, several pre-clinical models have been developed using rodents at a variety of different ages; however, key brain maturation events are overlooked that leave some age groups more or less vulnerable to injury. Thus, there has been a large emphasis on producing relevant animal models to elucidate molecular pathways that could be of therapeutic potential to help limit neuronal injury and improve behavioral outcome. TBI involves a host of different biochemical events, including disruption of the cerebral vasculature and breakdown of the blood brain barrier (BBB) that exacerbate secondary injuries. A better of understanding of the mechanism(s) underlying cerebral vascular regulation will aid in establishing more effective treatment strategies aimed at improving cerebral blood flow restoration and preventing further neuronal loss. Our studies reveal an age-at- injury dependence on the Angiopoetin-Tie2 axis, which mediates neuroprotection in a model of juvenile TBI following cortical controlled impact (CCI) that is not seen in adult mice. The protection observed was mediated, in part, by the microvascular response to CCI injury and prompted further detailed analysis of the larger arteriole network across several mouse strains and models of TBI. Our second study revealed both a model and species dependent effect on a specialized network of arteriole vessels, called collaterals after trauma. We demonstrated that a repetitive mild TBI (rmTBI) can induce collateral remodeling in C57BL/6 but not CD1 mice; however, CCI injury had no effect on collateral changes in either strain. Together, these findings demonstrate an age-dependent and species/model dependent effect on vascular remodeling that highlights the importance of individualized therapeutics to TBI. / Ph. D.

An astonishing number of deaths and related disabilities are attributed to traumatic brain injury (TBI) in the United States per year. Due to the unforeseeable nature of TBI and its association with the sequelae of other neurological comorbidities, research is centered around the secondary responses of brain mechanisms proceeding the initial mechanical injury. Blood brain barrier disruption is a well described driver of this secondary injury response and predictive marker of prognosis following TBI. Although BBB disruption plays a role in subsequent edema, inflammation, and the overall TBI outcome, the molecular mechanisms responsible for its regulation remain to be investigated. A large family of receptor tyrosine kinases, known as Eph receptors, that are important for axon growth and guidance embryonically and early-postnatally have been implicated in brain insults. Previous findings have shown that Eph expression is upregulated at the mRNA and protein level immediately following TBI. Moreover, ablation of Eph receptors on endothelial cells (ECs) revealed improved blood flow to the lesioned cortex in knockout (KO) mice compared to wild type (WT). Based on these results, we hypothesize that Eph receptors negatively regulate BBB permeability leading to neural dysfunction and motor deficits following TBI. To investigate this hypothesis, we characterized the temporal profile of the BBB, evaluated the EC-specific effects of Eph receptors, and used RNA sequencing to assess the cell-specific contributions following TBI in WT compared to KO mice. Our results show that EC-specific loss of Eph expression ameliorated BBB permeability at 6hr, 1-, 4-, and 7-days post injury (dpi) correlating with improved motor function at 7- and 14-dpi. Furthermore, mechanistic studies revealed increased mRNA expression of Tie2, Ang1, and the tight junction proteins Zona Occludens and Occludin in KO mice compared to WT. As well as, connection with neuronal processes. Based off of these findings, we utilized a soluble Tie2 inhibitor to elucidate the influence of Eph receptors on the Tie2/Ang pathway, and their role in mediating the effects seen. Tie2 inhibition of the KO mice revealed similar BBB disruption and lesion volume as WT 1dpi, attenuating the previous protection KO mice demonstrated. Future studies are necessary to understand other pathways that may be implicated in Eph receptor influence on endothelial cells such as inflammatory mediators and neurovascular crosstalk. This data provides evidence that Eph receptors negatively mediate EC response through downstream signaling of the Tie2/Ang pathway and may be a means of therapeutic target in the future. / Ph.D. / Traumatic brain injuries (TBIs) impact millions of individuals each year in the United States, making it a significant cause of death and disability. Furthermore, TBI has been linked to other comorbidities such as Alzheimers Disease, mood disorders, and epilepsy. Since the primary impact of a TBI cannot be predicted or prevented, research focuses on the secondary injury response as a therapeutic target to improve the outcomes following brain insult. Blood brain barrier (BBB) disruption is a well described consequence of TBI and has been correlated to a worse prognosis. The BBB normally provides a barrier between the circulating blood and the brain as protection and to maintain homeostasis. It is understood that decreased BBB integrity leads to subsequent edema, inflammatory response, and glial excitotoxicity, however, the mechanisms regulating this response remain to be investigated. Recent focus has been on a family of receptor tyrosine kinases, Eph receptors, that are unregulated following brain injury. Utilizing a mouse model, we can manipulate the temporal and spatial expression of Eph receptors to understand their role in the secondary injury cascade. Findings indicated that ablation of Eph receptors specifically on endothelial cells (ECs) resulted in preservation of BBB integrity at 1-, 4-, and 7- days following injury. Based on these results, we hypothesize that Eph receptor signaling on ECs negatively mediates BBB function and recovery following TBI. To test this hypothesis, we performed a comparative analysis between wild type (WT) and knockout (KO) mice on the expression of genes integral to BBB integrity, functional motor deficits, and loss of tissue in the lesion site following injury. We discovered significant decreases in lesion volume correlating with improvements in motor function in the KO mice compared to the WT. Moreover, KO mice showed increased expression of genes important for BBB maintenance such as Occludin and Tie2. To further discern the mechanism for these effects, we blocked Tie2 in the KO mice and observed similar negative prognostic indicators as in the WT. Future studies are warranted to understand the downstream signaling of Eph receptors on the Tie2 pathway. This data provides evidence that Eph signaling influences the BBB negatively following TBI through the Tie2 pathway and may be exploited for therapeutic means in the future.