This thesis examined how pharmacological treatment and cortical injury during development affects brain plasticity. Rats were given either a low dose of perinatal fluoxetine or a mild postnatal day 7 Hypoxic‐Ischemic (HI) injury, both, or neither. The functional outcome was assessed using a series of behavioral tasks and anatomical measures. To assess how HI affects the development of motor maps, forelimb motor maps were evoked at P19. The findings indicate that fluoxetine treatment or HI injury mostly negatively affected functional outcome. The combined treatment with fluoxetine and HI injury only interacted on a limited number of measures. There was no delay in the emergence of evoked motor movements, or change in map location in the HI animals. These results suggest that the pharmacological treatment and cortical injury described in this thesis may have different mechanisms whereby plastic changes are induced and the interaction between these two mechanisms is limited. / xii, 169 leaves : ill. ; 29 cm.

Studies of sustained-attention retraining following brain injury are reviewed, and found to have produced inconclusive results. The reason for this, it is suggested, is that a standard operational analysis of attention has not been applied, as evidenced by considerable inconsistency in the dependent measures and treatment methods used from study to study. The present study addresses this concern by applying well established principles of operant conditioning to the analysis and remediation of attention deficits. After briefly reviewing the variety of task parameters in the attention literature, noting ambiguities inherent in the various conceptualizations of attention, it is decided to train vigilance task performance, a relatively unambiguous and uncontroversial operational definition of sustained attention. Both the principle of immediacy, of reinforcement (feedback of correct and incorrect on each trial) and shaping (gradual increase of speed demands contingent on increased performance accuracy) are employed. The issue of generalization is deemed central to concerns of treatment efficacy, and is explored by administration of alternate versions of the same basic vigilance task. Results show that training with immediate reinforcement and speed-shaping produced better acquisition of the trained task than delayed feedback and invariant speed of stimulus presentation. Furthermore, gains resulting from training were essentially limited to the task on which training was conducted, with little evidence for generalization to like tasks employing different stimuli. These results are discussed in terms of the applicability of the construct of sustained attention to head injury rehabilitation. / Graduate

The development of emergency department medical interventions and the implementation of fast-transport trauma systems has decreased the rate of death resulting from traumatic brain injury (TBI). Without corresponding methods for long-term treatment and recovery, the prevalence of people disabled by TBI has increased, creating a growing public health problem. Investigations generated by physicians, rehabilitation programs, and social scientists, which attempt to associate standard measures of injury severity with outcome, leave unexplained variance in long-term functional status for persons with TBI. The purpose of this investigation was to use persons with brain injury and their family members, to guide an analysis of the factors that foster successful recovery from brain injury. Three studies were conducted. In Study #1, the method for observation generated by Kurt Goldstein (1934) was adopted to conduct 20 case studies of persons who sustained brain injury. The Schema of the EsEx Couple (Maynard. 1992) was used to orient the investigation. The EsEx Couple Schema proposes that events in human life must be understood by considering the whole system of Person (Essence) in the Environment (Exchange), and the transactions that flow in a recursive loop from Person to Environment and back. Kurt Goldstein's Laws of Organismic Life (1934), a model consistent with that of the EsEx Couple, was used to evaluate the data. Strong patterns associated family and social networks, autonomy, and perceived self-determination with higher levels of recovery, and were used to generate a Model for Recovery. In Study #2. the Motivational Analysis of Self-Systems Processes (Connell & Wellborn, 1991) was combined with results from Study #1 to generate a Development Model, and to build a survey which was administered to 248 persons with brain injury. Results (1) confirmed the model, indicating factors that contribute to recovery were hypothesized measures of Social Context, Perception, and Engagement; and (2) established a valid instrument, generated by persons with brain injury and their families, for measuring functional status. In Study #3. results of the survey research were used to return to the case studies to consider where individual lives differ from expected patterns, and why. Deviations from expected patterns were explored to identify how individual differences operate to affect outcome. Recommendations for clinical practice include (1) directing interventions toward family as well as patient, as a method of enhancing the Social Context for the patient, and (2) using careful evaluation of each patient's idiosyncrasies to consider individual interventions.

Glial cells maintain homeostasis that is essential to neuronal function. Injury to the nervous system leads to the activation and proliferation of glial cells and pericytes, which helps to wall off the damaged region and restore homeostatic conditions. Sonic hedgehog is a mitogen which is implicated in injury-induced proliferation of glial cells and pericytes. The mitogenic effects of sonic hedgehog require primary cilia, but the few reports on glial or pericyte primary cilia do not agree about their abundance and did not address effects of injury on these cilia. Primary cilia are microtubule-based organelles that arise from the centrosome and are retracted before cells divide. Depending on cell type, proteins concentrated in cilia can transduce several mitotic, chemosensory, or mechanosensory stimuli. The present study investigated effects of stab wound injury on the incidence and length of glial and pericyte primary cilia in the area adjacent to the injury core. Astrocytes, polydendrocytes and pericytes were classified by immunohistochemistry based on cell-type markers. In normal adult mice, Arl13b immunoreactive primary cilia were present in a majority of each cell type examined: astrocytes, 98±2%; polydendrocytes, 87±6%; and pericytes, 79±13% (mean ± SEM). Three days post-injury, cilium incidence decreased by 24% in astrocytes (p< 0.008) and 41% in polydendrocytes (p< 0.002), but there was no significant effect in pericytes. Polydendrocytes labeled with the cell cycle marker Ki67 were less likely to have cilia compared to resting, Ki67- polydendrocytes. Considering post-injury rates of proliferation for astrocytes and polydendrocytes, it appears that resorption of cilia due to cell cycle entry may account for much of the loss of cilia in polydendrocytes but was not sufficient to account for the loss of cilia in astrocytes. Under normal conditions, astrocytes rarely divide, and they maintain non-overlapping territories. However, three days after injury, there was a 7-fold increase in the number of paired mirror-image astrocytes (p< 0.018), which are most likely daughter cells from astrocytes that recently divided. Cilia incidence tended to decrease in these pairs compared to single astrocytes (p< 0.057) in injured mice. This is the first systematic investigation of cilia of astrocytes, polydendrocytes, and pericytes in the brain. Moreover, the examination of effects of brain injury on cilia adds to the understanding of injury-induced proliferation in these cells.

Traumatic brain injury (TBI) is a major problem with an estimated cost of $76 billion per year in the US alone. The Center for Disease Control and Prevention (CDC) documented 2.53 million TBI-related emergency department visits, with approximately 288,000 TBI-related hospitalizations and 56,800 TBI-related deaths in 2014 in the US. The lack of FDA-approved treatment strategies for TBI drives the need for novel therapeutic and preventative measures. In a quest to reduce TBI-related injuries and deaths, automotive companies have focused their efforts to make safer cars for both occupants and pedestrians. Computational finite element (FE) models have been used to advance research efforts in automotive safety systems engineering in hopes of ameliorating the burden caused by TBI. The current use of FE models in the automotive industry focuses on predicting stresses and strains that occur during the accident itself to predict primary injury. However, contemporary models lack the appropriate mechanical properties required to make accurate predictions of brain tissue deformation after injury and lack the ability to model secondary injuries such as cerebral edema (brain swelling). With cerebral edema being a major cause of death and disability after TBI, and with the pattern and magnitude of cerebral edema being dependent on the initiating strain field in brain tissue during TBI, automotive safety systems could be further improved if 1) FE head models contained more accurate mechanical properties and 2) if FE models could simulate secondary injuries such as cerebral edema. Therefore, the driving purpose of this thesis is two-fold: 1) to determine the mechanical properties of different regions of the brain and 2) to present a new computational methodology that allows for modeling of cerebral edema to better predict patient outcome following TBI. The use of FE models requires appropriate constitutive formulations and associated parameters to accurately model and predict the initial mechanical response of the brain to injury loading conditions. Since patient outcome is dependent on the resulting strain field within brain tissue post-injury, accurate modeling of brain tissue deformation is important for testing the efficacy of engineered automotive safety systems using FE simulations. To address this need, the first aim of this thesis employed an inverse FE approach to characterize mechanical properties of the human hippocampus (CA1, CA3, dentate gyrus), cortex white matter, and cortex gray matter. Anatomical regions were significantly different in their mechanical properties. Although no sex dependency was observed, there were trends indicating that some male brain regions were generally stiffer than corresponding female regions. In addition, mechanical properties were not dependent on age within the examined age range (4-58 years old). Ultimately, this study provides a structure-specific description of fresh human brain tissue mechanical properties, which will be an important step toward explicitly modeling the heterogeneity of brain tissue deformation during TBI using FE modeling. Fatal brain injuries may also result from physiological changes in the brain that occur after the primary injury that immediately occurs during head injury. Secondary injuries such as cerebral edema are associated with poor outcome. Despite the severe consequences of cerebral edema, its mechanism is not fully understood. The second aim of this thesis, therefore, was to elucidate the driving mechanism of cerebral edema by demonstrating that cleavage of intracellular fixed-charge density (FCD) reduces brain swelling pressure and to measure the FCD content of rat and pig brain tissue. Thin brain samples were placed into a confined pressure chamber, and FCD content was calculated from measured swelling pressure and the Gibbs-Donnan equation. We observed that cleavage of FCD using enzymes reduced swelling pressure in rat brain tissue samples and determined that pig cortex gray matter contains more FCD than pig cortex white matter. These results demonstrate that cerebral edema may occur in accordance with principles of triphasic swelling biomechanics and demonstrates the plausibility of computationally modeling cerebral edema with triphasic material formulations. Cerebral edema leads to increased intracranial pressure (ICP) as the brain swells within the fixed volume of the skull, and there is overwhelming evidence of ICP as a powerful predictor of patient outcome following TBI. Current industry standards of patient outcome evaluation use tissue-level metrics solely from primary injury such as maximum principal strain (MPS) or cumulative strain damage measure (CSDM), but these methods can be improved especially in regards to predicting mortality. Therefore, the third aim of this thesis was to develop a new FE head model and computational methodology incorporating triphasic swelling biomechanics to simulate brain swelling following impact to improve patient outcome predictions. Patient outcome was predicted by simulating swelling and calculating the resulting ICP, which is a strong indicator of patient mortality. Calculating ICP in addition to predicting primary injury metrics such as MPS and CSDM may allow automotive safety engineers to make better predictions of patient outcome following TBI so they can develop better safety systems. Another common indicator of poor outcome following TBI is acute subdural hematoma (ASDH). ASDH is an intracranial bleed that often results from TBI because of stretching and tearing of the bridging veins which causes blood to collect in the innermost layer of the dura. Despite the poor prognosis associated with the presence of ASDH following TBI, the mechanism as to why its presence is associated with a higher likelihood of death remains uncertain. Current state of the art FE head models used in automotive safety engineering efforts do not consider ASDH, which may drastically reduce their effectiveness in predicting patient outcome following TBI. Therefore, the fourth and final aim of this thesis was to incorporate ASDH into our FE head model of swelling and elucidate the underlying secondary brain injury mechanism of ASDH that contributes to increased mortality in hopes of increasing the efficacy of current FE models to predict patient outcome and ultimately design better safety systems. Using our novel FE head model and methodology from aim 3, we showed that the higher likelihood of death associated with the presence of ASDH may be caused by exacerbated ischemic injury which increases ICP, demonstrating that modeling of ASDH is necessary for accurately modeling patient outcome following TBI. Despite decades of TBI research and FE head model improvements, more work is required to enhance the biofidelity of these models to better predict patient outcome. The work in this thesis is important, as it introduces a new tool that will allow automotive safety engineers to incorporate cerebral edema and ASDH, both of which may drastically influence patient outcome following TBI, into models of head injury to allow for better predictions of patient outcome. It is hoped that the work in this thesis lays the foundation for future work that aids in the design of improved automotive safety systems that will save countless human lives.

This autoethnography explores the phenomenon of marriage after traumatic brain injury (TBI). Capturing as its data, through a series of audio-recorded conversations and journal entries, the first-hand, co-constructed experiences of a married couple, it provides an ‘insider’ and as such, intimate perspective on life together following such an unexpected, disruptive and life-altering event. Situated within ‘a systemic constructionist’ epistemology, it spotlights, in particular, the relational aspects of the post-TBI marriage unfolding over time, rather than just the individual perspectives of each spouse at a single point in time - as most existing studies on the topic do. As a qualitative study, it made allowance for the collection and use of rich, nuanced data so as to do some justice to the complex nature of the topic being studied. David Reiss’ explanatory theory on ‘crisis and the development of the family paradigm’ was applied deductively during the carrying out of a thematic analysis of the data, with the intention of bringing new insights to the understanding of the phenomenon of the post-TBI marriage. Data were also analysed inductively, in that themes emerging from the data itself were also used. A discussion based on the findings of the data analysis was proffered. Based on these findings, recommendations on what issues therapists working from within a family-systems orientation might focus their attention on were made. A recommendation for TBI couples to receive support from early intervention and follow-up services was also made, along with identifying the consequent need for research first to be done on developing and implementing such a service / Psychology / M.A. (Psychology)

Background: The hippocampus and corpus callosum have been shown to be vulnerable in head injury. Various neuroimaging modalities and quantitative measurement techniques have been employed to investigate pathological changes in these structures. Cognitive and behavioural deficiencies have also been well documented in head injury. Aims: The aim of this research project was to investigate structural changes in the hippocampus and corpus callosum. Two different quantitative methods were used to measure physical changes and neuropsychological assessment was performed to determine cognitive and behavioural deficit. It was also intended to investigate the relationship between structural change and neuropsychology at 1 and 6 months post injury. Method: Forty-seven patients with head injury (ranging from mild to severe) had undergone a battery of neuropsychological tests and an MRI scan at 1 and 6 months post injury. T1-weighted MRI scans were obtained and analysis of hippocampus and corpus callosum was performed using region-of-interest techniques and voxel-based morphometry which also included comparison to 18 healthy volunteers. The patients completed neuropsychological assessment at 1 and 6 months post injury and data obtained was analysed with respect to each assessment and with structural data to determine cognitive decline and correlation with neuroanatomy. Results: Voxel-based morphometry illustrated reduced whole scan signal differences between patients and controls and changes in patients between 1 and 6 months post injury. Reduced grey matter concentration was also found using voxel-based morphometry and segmented images between patients and controls. A number of neuropsychological aspects were related to injury severity and correlations with neuroanatomy were present. Voxel-based morphometry provided a greater number of associations than region-of-interest analysis. No longitudinal changes were found in the hippocampus or corpus callosum using region-of-interest methodology or voxel-based morphometry. Conclusions: Decreased grey matter concentration identified with voxel-based morphometry illustrated that structural deficit was present in the head injured patients and does not change between 1 and 6 months. Voxel-based morphometry appears more sensitive for detecting structural changes after head injury than region- of-interest methods. Although the majority of patients had suffered mild head injury, cognitive and neurobehavioural deficits were evidenced by a substantial number of patients reporting increased anxiety and depression levels. Also, the findings of relationships between reduced grey matter concentration and cognitive test scores are indicative of the effects of diffuse brain damage in the patient group.

This study examined the neurocognitive skills, incidence of mild head injury, incidence of learning disabilities, and study habits among college students with grade point average of 2.00 or below (N = 25) as contrasted with college students with grade point average above 2.00 (N = 70). The intent of this research was to extend the work of Segalowitz and Brown (1991) and Segalowitz and Lawson (1993) who found significant associations between reported history of mild head injury and developmental disabilities among high school and college samples. MANOVAs conducted on measures of academic achievement, global cognitive skills, verbal and nonverbal memory, motor and tactile functioning, and study habits did not discriminate between probationary and non-probationary students. Probationary and non-probationary students also did not differ with regard to incidence of reported head injury, frequency of diagnosed learning disabilities, and study habits. Measures of neurocognitive functioning and study habits did not contribute to the prediction of grade point average over and above that predicted by Scholastic Aptitude Test composite score. Several exploratory analyses were performed examining the relationship between study habits and neurocognitive skills. Gender differences, implications for future research and development of study skills courses, and limitations of this study were discussed.

When children have a moderate to severe traumatic brain injury (TBI), they are treated in a continuum of care that includes triage and emergency care, hospitalization, rehabilitation and outpatient therapy. Physical and cognitive recovery from brain injury may take several years. Children’s recovery varies, depending on numerous factors including pre-injury conditions and injury severity. While children and families are eager to return home to familiar activities, there are often significant physical, cognitive, behavioral and emotional changes that challenge families. Successful community reintegration depends on the ability of the family to understand and support the child, dealing with and responding effectively to those challenges. The purpose of this study is to understand how parents manage the care and community reintegration of their child who has experienced a TBI over time. This study utilized a mixed methods approach exploring the dimensions of the health challenge faced by parents caring for a child after a TBI, critical turning points as they face health challenges, and approaches for movement toward resolving health challenges. Story theory and story inquiry method were used to gather stories from 10 parents of children who experienced moderate to severe traumatic brain injury between the ages of 12 and 18, and between 2 and 5 years ago. Parents’ perceptions of their child’s quality of life and their ability to manage their child’s health challenge were explored using the Pediatric Quality of Life Inventory and Family Management Measure. Health challenges identified were: living with overwhelming personal upheaval, navigating the unknown, and struggling with how to support independence/dependence. Turning points were chronological or epiphanies. Approaches for movement toward resolving were continuously re-creating a new normal, being fully engaged in meeting the needs of one’s child, and embracing caring relationships to construct the new normal. Qualitative and quantitative data were analyzed to synthesize the findings. Results include a sense of ease in managing the health condition of the child associated with continuously creating a new normal. Healthcare providers can support and strengthen family management of children after TBI by understanding the health challenge, critical turning points and how parents move toward resolving. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

During a traumatic insult to the brain, tissue is subjected to large stresses at high rates which often surpass cellular thresholds leading to cell dysfunction or death. Cellular events that occur at the time of and immediately after an insult are poorly understood. Immediately following traumatic brain injury (TBI), the neuronal plasma membrane may become disrupted and potentiate detrimental pathways by allowing extracellular contents to gain access to the cytosol. In the current study, neuronal plasma membrane disruption was assessed in vivo following moderate unilateral controlled cortical impact in rats using a normally cell-impermeant fluorescent compound as a plasma membrane permeability marker. This fluorescent dye was injected into the cerebrospinal fluid and was allowed to diffuse into the brain. TBI caused a widespread acute disruption of neuronal membranes which was significantly different compared to uninjured brains. Affected cells were present in cortex and hippocampal regions. These findings were complemented by an in vitro model of TBI where membrane disruption was quantified and its mechanisms elucidated. Permeability marker(s) were added to neuronal cultures before the insult as indicators for increases in plasma membrane permeability. The percentage of cells containing the permeability marker was dependent on the molecular mass, as smaller molecules gained access to a higher percentage of cells than larger ones. Permeability increases were also positively correlated with the rate of insult. Membrane disruption was transient, evidenced by a robust resealing within the first minute after the insult. In addition, membrane resealing was found to be dependent on extracellular Ca2+, as chelation of the ion abolished a significant amount of resealing. We have also investigated the effects of mechanically-induced plasma membrane disruptions on neuronal network electrical activity. We have developed a multielectrode array system that allows the study of electrical activity before, during, and after a traumatic insult to neurons. Endogenous electrical activity of neuronal cultures presented a heterogeneous response following mechanical insult. Moreover, spontaneous firing dysfunction induced by injury outlasted the presence of membrane disruptions. This study provides a multi-faceted approach to elucidate the role of neuronal plasma membrane disruptions in TBI and its functional consequences.