The 567-item MMPI-2 is the most widely used personality measure; it requires a sixth-grade reading level, takes 60-90 minutes to administer, and reports robust psychometrics. However, traumatic brain injury (TBI) sequelae can cause cognitive deficits that affect test-taking abilities and item endorsement during differential diagnoses of neurological and personality factors. Therefore, this study examined the clinical utility of the shortened 338-item MMPI-2-RF inventory with a post-acute TBI population as a practical alternative. The MMPI-2-RF requires a fifth-grade reading level and takes 35-50 minutes to administer. The MMPI-2-RF also includes revised versions of the MMPI-2 Validity Scales and new substantive scales that may better psychometrically account for personality in TBI sequelae, such the Somatic/Cognitive Scales. This study conducted an incremental validity analysis of the MMPI-2-RF with a non-litigating, post-acute care TBI population in Central Texas. The goal of the study was to explore the measure’s performance, or its ability to capture functional dimensions in a TBI sample. More specifically, the study examined the construct validity of MMPI-2 to MMPI-2-RF Validity and Restructured Clinical Scales, and criterion validity for the Somatic/Cognitive Scales with neuropsychological and neurobehavioral functioning measures. An archival neuropsychological database (N = 60) was analyzed of patients who participated in TBI rehabilitation treatment at a Central Texas hospital. MMPI-2-RF profiles were retrospectively scored with MMPI-2 archival data. Statistical analysis between MMPI-2 to MMPI-2-RF Validity and Restructured Clinical Scales was conducted. MMPI-2-RF Somatic/Cognitive Scales and criterion measures of Weschler Adult Intelligence Scale, 4th Edition (WAIS-IV), The Weschler Memory Scales, 4th Edition (WMS-IV), The Booklet Category Test, 2nd Edition (BCT), and the Neurobehavioral Functioning Inventory (NFI) were examined. Patient demographics and measurement qualities were reported with the sample. / text

Traumatic brain injury is one of the leading causes of death and disability in the North America, and can result in long-term physical and psychological consequences, which over time change brain injury from a medical problem to an issue of quality of life. Various self-care activities can significantly improve the quality of life in people living with a chronic health condition. However, research on self-care in these populations has focused on the physical aspect of self-care, often excluding other domains of functioning. There is minimal self-care research involving people who had a traumatic brain injury; however, it is important to understand how they experience and make sense of their injury and its consequences in order to develop more effective approaches to their rehabilitation and support systems. In this study, I interviewed adults with traumatic brain injury who had their injury at least two years prior to the study. Narrative analysis of their stories revealed that the participants faced the following difficulties: constructing an explanation for the injury, dealing with losses and limitations, feeling misunderstood and insignificant, and dealing with memory deficits and physical problems. The ways in which participants tried to overcome these difficulties was understood as self-care. It manifested in a variety of ways, including deliberate health-related behaviours, changes in one’s way of thinking, emotional regulation strategies, and linguistic and paralinguistic means used in the narratives. I discuss ways to understand the findings using different theoretical models, such as illness narratives, social disenfranchisement, and social disability models. The results of the study strongly suggest that our understanding of self-care should encompass both physical and psychological health.

Traumatic brain injury is one of the leading causes of death and disability in the North America, and can result in long-term physical and psychological consequences, which over time change brain injury from a medical problem to an issue of quality of life. Various self-care activities can significantly improve the quality of life in people living with a chronic health condition. However, research on self-care in these populations has focused on the physical aspect of self-care, often excluding other domains of functioning. There is minimal self-care research involving people who had a traumatic brain injury; however, it is important to understand how they experience and make sense of their injury and its consequences in order to develop more effective approaches to their rehabilitation and support systems. In this study, I interviewed adults with traumatic brain injury who had their injury at least two years prior to the study. Narrative analysis of their stories revealed that the participants faced the following difficulties: constructing an explanation for the injury, dealing with losses and limitations, feeling misunderstood and insignificant, and dealing with memory deficits and physical problems. The ways in which participants tried to overcome these difficulties was understood as self-care. It manifested in a variety of ways, including deliberate health-related behaviours, changes in one’s way of thinking, emotional regulation strategies, and linguistic and paralinguistic means used in the narratives. I discuss ways to understand the findings using different theoretical models, such as illness narratives, social disenfranchisement, and social disability models. The results of the study strongly suggest that our understanding of self-care should encompass both physical and psychological health.

Woodpeckers can withstand 1200-1400 g of force during repetitive pecking. The forces a woodpecker’s skull and brain are subjected to warrants an in-depth investigation for the possible existence of neuro-trauma. Dr. Philip May and colleagues in 1976 published a paper titled “Woodpeckers and Head Injury” detailing two woodpeckers and one toucan control. The group utilized ferrocyanide staining, a general stain used for detecting iron deposits, on the sections. The results of these stains were not reported in Dr. May’s paper, yet he and his colleagues conclude that “clearly the woodpecker’s brain is protected somehow from impact and vibration injury.” Close to 115 journal articles have cited this one paper as the standard for woodpeckers not incurring brain injury during pecking. Due to limited studies on the woodpecker brain and the fact the woodpecker is a model for advancing helmet technology, we set out to study the woodpecker’s brain for signs of injury. Taking 10 different ethanol preserved woodpeckers from all parts of the world in different climates, and five non-woodpecker, ethanol preserved red-winged black bird experimental controls, paraffin embedded sections were cut and stained. A piece of human Alzheimer’s disease cortex was also used as a positive control. We utilized Gallyas silver stain for the study of neurofibrillary tangles and tauopathies as well as anti-phospho-tau and anti-glial fibrillary acidic protein (GFAP) immunostaining to detect tau protein and GFAP respectively. The results demonstrated perivascular silver-positive deposits in the superficial cortex and axonal tract injury of eight out of the 10 woodpeckers. The anti-phospho-tau immunostaining stained axonal tract injury in two of the three woodpeckers studied. The red-winged back birds demonstrated no positivity for all three stains. The Alzheimer’s positive control showed silver positive and phospho-tau positive staining as expected. This is the first study of this kind to discover and label potential brain injury in the woodpecker model. The negative staining of the red-winged black bird controls contrasted with the positive staining woodpecker sections suggest pecking in the woodpecker may induce brain injury. When addressing the development of safety equipment, the use of the woodpecker model should be approached with caution. Moving forward, research into different immunostaining molecular targets and an age controlled woodpecker and experimental control study should be performed to determine if the brain injury seen with our research is age-dependent.

Traumatic brain injury (TBI) is a common event that can lead to profound consequences for the individual involved, and a considerable socio-economic cost. The initial injury event triggers a series of secondary brain injury mechanisms that lead to further mortality and contribute to morbidity. One classical injury pathology is termed traumatic axonal injury (TAI), which in clinical settings produces the picture of diffuse axonal injury. TAI occurs both as a primary insult, and as a consequence of secondary mechanisms. One secondary injury mechanism that worsens TAI may be Wallerian degeneration (WD), a cell-autonomous axonal death pathway. The relationship between traumatic axonal injury and WD is poorly characterised. This thesis explores the basic mechanisms by which a physical axonal trauma can lead to WD, and how modulation of the WD pathway can affect the cellular responses to a traumatic injury. This involves the development and characterisation of in vitro and in vivo models of traumatic axonal injury. These models are then used to explore the response of cellular cultures to injury when treated with pharmacological and genetic modulators of WD. Using a primary neuronal stretch-injury system we demonstrate that rates of neurite degeneration are altered by modulators of the WD pathway but that a purported neuroprotective compound ‘P7C3-A20’ did not protect primary cultures in vivo and did not act via a WD dependent mechanism. An organotypic hippocampal slice stretch injury model was then used to demonstrate genetic rescue of cellular death, and used to assess amyloidogenic responses to injury. Next we established a TBI model using Drosophila Melanogaster, and demonstrated that a loss of function mutation in a key WD gene ‘highwire’ which controls NMNAT levels, was capable of rescuing premature death and a range of behavioral deficits after a high impact trauma. The injury caused dopaminergic neuronal loss and this was rescued by highwire mutation. Furthermore, this dopaminergic neuronal protection extended to a genetic PINK1 model of Parkinsonism. Together these results help establish WD as an important secondary injury mechanism in TBI, and provide evidence that modulation of the WD pathways can improve outcomes in various model systems. This provides a foundation for future translational research into the fields of WD and TBI.

Previously, we have demonstrated that nicotinamide (NAm), a neuroprotective soluble B-group vitamin, improves recovery of function following traumatic brain injury (TBI). However, no prior studies have examined whether NAm is beneficial following continuous infusions over seven days post-TBI. The purpose of this study was to investigate the preclinical efficacy of NAm treatment as it might be delivered clinically; over several days by slow infusion. Rats were prepared with either unilateral controlled cortical impact (CCI) injuries over the somatosensory cortex (SMC) or sham procedures and divided into three groups: CCI-NAm, CCI-vehicle, and sham. Thirty minutes following CCI, Alzet osmotic mini-pumps were implanted subcutaneously. NAm was delivered at a rate of 50 mg/kg/day for seven days immediately post-CCI. On day seven following injury, the pumps were removed and blood draws were collected for serum NAm and nicotinamide adenine dinucleotide (NAD+) analyses. Starting on day two post-CCI, animals were tested on a battery of sensorimotor tests (bilateral tactile adhesive removal, locomotor placing, and limb-use asymmetry). Statistical analyses of the tactile removal and locomotor placing data revealed that continuous administration of NAm significantly reduced the initial magnitude of the injury deficit and improved overall recovery compared to the vehicle-treated animals. NAm treatment also significantly decreased limb-use asymmetry compared to vehicle-treated animals. Continuous infusion of NAm resulted in a significant serum elevation in NAm, but not NAD+, as well as significantly attenuated cortex tissue loss than un-treated animals. The NAm-treated group also had the lowest number of glial fibrillary acidic protein (GFAP) positive cells. No detrimental effects were seen following continuous infusion. The present results suggest that NAm delivered via a clinically relevant therapeutic regimen may truncate behavioral damage following TBI. Thus our results offer strong support for translation into the clinical population.

AN ABSTRACT OF THE THESIS OF AIDAN CHRISTIE SMITH, for the MASTER OF ARTS degree in PSYCHOLOGY, presented on OCTOBER 27th, 2017, at Southern Illinois University Carbondale. TITLE: EFFECTS OF NICOTINAMIDE ON MICROGLIAL RESPONSE IN JUVENILE RATS AFTER CONTROLLED CORTICAL IMPACT MAJOR PROFESSOR: Dr. Michael J. Hylin Traumatic brain injury (TBI) is a leading cause of death, cognitive and behavioral disability in children in industrialized nations. Preclinical trials of nicotinamide (NAM) treatment provide neuroprotection and reduced inflammatory responses in adult models of TBI. The primary goal of this study was to address the neuroprotective effects of NAM in the developing brain, specifically, the microglial response that occurs following injury. Animals received a bilateral craniotomy with a single cortical contusion injury over the parietal lobe and were treated with either 500mg/kg of nicotinamide or 0.9% saline via intraperitoneal injection. Animals received three injections, 15 minutes, 24 hours, and 48 hours after injury, and were sacrificed at 4 time points, 3 hours, 72 hours, 1 week, or 1 month following injury. Brains were then used for histological assessment for microglial activity. The results show that NAM attenuates the activation of microglia after CCI. Over the course of time, saline treated animals had a marked increase in microglia at 72 hours and remained elevated after 1 week. In NAM treated animals however, there was no significant increase in the number of microglia at any time point. It is suggested here that NAM has a great effect on the inflammatory response. Further studies are needed to examine NAM’s effects on behavior and functional recovery.

abstract: Approximately 2.8 million Americans seek medical care for traumatic brain injury (TBI) each year. Of this population, the majority are sufferers of diffuse TBI, or concussion. It is unknown how many more individuals decline to seek medical care following mild TBI. This likely sizeable population of un- or self-treated individuals combined with a lack of definitive biomarkers or objective post-injury diagnostics creates a unique need for practical therapies among diffuse TBI sufferers. Practical therapies stand to decrease the burden of TBI among those who would otherwise not seek treatment or do not meet clinical diagnostic criteria upon examination. For this unique treatment niche, practical therapies for TBI are defined as having one or more of the following qualities: common availability, easy administration, excellent safety profile, and cost-effectiveness. This dissertation identifies and critically examines the efficacy of four classes of practical treatments in improving rodent outcome from experimental diffuse traumatic brain injury. Over-the-counter (OTC) analgesics, omega-3 fatty acids, specialized pro-resolving mediators (SPMs), and remote ischemic conditioning (RIC) were administered before or following midline fluid percussion injury. Behavioral, histological, and molecular analyses were used to assess treatment effects on functional outcome and secondary injury progression. Acute administration of common OTC analgesics had little effect on post-injury outcome in mice. Dietary supplementation with omega-3 fatty acid docosahexaenoic acid (DHA) prior to or following diffuse TBI significantly reduced injury-induced sensory sensitivity and markers of neuroinflammation with no effect on spatial learning. Intraperitoneal administration of omega-3 fatty acid-derived SPM resolvin E1 significantly increased post-injury sleep and suppressed microglial activation. Aspirin-triggered (AT) resolvin D1 administration improved both motor and cognitive outcome following diffuse TBI. RIC treatment in mice demonstrated little effect on functional outcome from diffuse TBI. Untargeted proteomic analysis of plasma samples from RIC-treated mice was used to identify candidate molecular correlates of RIC. Identification of these candidates represents a vital first step in elucidating the neuroprotective mechanisms underlying RIC. The overall findings suggest that omega-3 fatty acid supplementation, SPM administration, and RIC may serve as effective practical therapies to reduce the somatic, cognitive, and neurological burden of diffuse TBI felt by millions of Americans. / Dissertation/Thesis / Doctoral Dissertation Neuroscience 2017

There is increasing evidence that repeat mild traumatic brain injury (rmTBI) may result in cumulative and long-term symptoms, more pronounced behavioural deficits, and neurodegeneration. Children have a greater susceptibility to head injury and represent a significant at risk population for rmTBI, especially those that participate in contact sports. Despite this, there is a paucity of data on rmTBI pathophysiology in the juvenile brain. The current study utilizes a novel awake closed head injury (ACHI) model to deliver repeat injuries to fully conscious juvenile rats. The ACHI model avoids the potential confounds of anaesthesia, and facilitates the assessment of neurological function immediately after each impact. Results indicate that the ACHI model produces acute neurological deficits after each impact, and that repeat injury worsens outcomes. Behavioural testing identified transient anxiety-like behaviour and motor impairment in response to rmTBI. The functional impairments and affective behaviour were in the absence of tau protein pathology. This study represents the first investigation of the consequences of rmTBI on the juvenile brain using an awake model of brain injury. / Graduate

Traumatic brain injury (TBI) is one of the leading causes of death and disability in children. The prefrontal cortex (PFC) is most susceptible to injury which leads to deficits in executive function, sociability, and cognitive flexibility. The oxytocin (OT) system plays a significant role in the modulation of species-typical social behaviors, such as social recognition and memory. Intranasal OT (IN-OT) has been shown to be neuroprotective against neuronal insults and social deficits through various mechanisms. Due to this and OT’s role in the modulation of social behaviors, it is possible that IN-OT could improve the social deficits caused by a PFC injury. The primary goal of this study was to determine the effects of a TBI on the development of the OT system. The secondary goal was to address the efficacy of IN-OT as a treatment for the social deficits observed following a TBI. For these studies, animals received a single cortical contusion injury bilaterally damaging the medial pre-frontal cortex. Immediately following injury (1-2 minutes), animals were given a single dose of IN-OT (20 μg, 1 μg/1 μl Ringer’s solution), placebo, or no treatment and sacrificed at days 1, 14, and 30 post-injury. Animals were assessed using behavioral and histological measures. It was predicted that animals that received IN-OT would demonstrate fewer social deficits on the behavioral measures and a smaller lesion size. Additionally, it was expected that a TBI would increase inflammation levels and decrease the levels of OT and OT receptors compared to sham animals. The results indicate that OT treatment did not significantly improve histopathological outcomes. However, the vehicle that was utilized impaired outcomes. Additionally, there was minimal changes to the OT system at the injury site, in the anterior olfactory nucleus, and in the caudate putamen due to injury. But vehicle treatment altered the expression levels of the OT peptide and receptors. Behaviorally, OT treatment improved performance in the Morris water maze in TBI animals compared to vehicle-treated and untreated TBI animals, but not other behaviors. However, vehicle-treated, and OT-treated animals were more likely to be aggressive than expected and untreated sham animals were less likely to be aggressive than expected. Taken together, it was observed that administration of a hypotonic saline solution following TBI significantly increases pathophysiology after TBI, and these effects translate into increased aggression levels. Although, learning and memory remained unaffected by the vehicle. Thus, further studies are needed to examine the effects of OT on TBI for behavioral and pathophysiological improvements.