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Emotion recognition and traumatic brain injury

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Emotion recognition through facial expression plays a critical role in communication. Review of studies investigating individuals with traumatic brain injury (TBI) and emotion recognition indicates significantly poorer performance compared to

Emotion recognition through facial expression plays a critical role in communication. Review of studies investigating individuals with traumatic brain injury (TBI) and emotion recognition indicates significantly poorer performance compared to controls. The purpose of the study was to determine the effects of different media presentation on emotion recognition in individuals with TBI, and if results differ depending on severity of TBI. Adults with and without TBI participated in the study and were assessed using the The Awareness of Social Inferences Test: Emotion Evaluation Test (TASIT:EET) and the Facial Expressions of Emotion-Stimuli and Tests (FEEST) The Ekman 60 Faces Test (E-60-FT). Results indicated that individuals with TBI perform significantly more poorly on emotion recognition tasks compared to age and education matched controls. Additionally, emotion recognition abilities greatly differ between mild and severe TBI groups, and TBI participants performed better with the static presentation compared to dynamic presentation.

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Created

Date Created
  • 2011

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Long-term EEG dynamics following traumatic brain injury in a rat model of post traumatic epilepsy

Description

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

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.

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Date Created
  • 2012

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Service-related conditions and higher-order cognitive processing in military veteran college students

Description

Military veterans have a significantly higher incidence of mild traumatic brain injury (mTBI), depression, and Post-traumatic stress disorder (PTSD) compared to civilians. Military veterans also represent a rapidly growing subgrou

Military veterans have a significantly higher incidence of mild traumatic brain injury (mTBI), depression, and Post-traumatic stress disorder (PTSD) compared to civilians. Military veterans also represent a rapidly growing subgroup of college students, due in part to the robust and financially incentivizing educational benefits under the Post-9/11 GI Bill. The overlapping cognitively impacting symptoms of service-related conditions combined with the underreporting of mTBI and psychiatric-related conditions, make accurate assessment of cognitive performance in military veterans challenging. Recent research findings provide conflicting information on cognitive performance patterns in military veterans. The purpose of this study was to determine whether service-related conditions and self-assessments predict performance on complex working memory and executive function tasks for military veteran college students. Sixty-one military veteran college students attending classes at Arizona State University campuses completed clinical neuropsychological tasks and experimental working memory and executive function tasks. The results revealed that a history of mTBI significantly predicted poorer performance in the areas of verbal working memory and decision-making. Depression significantly predicted poorer performance in executive function related to serial updating. In contrast, the commonly used clinical neuropsychological tasks were not sensitive service-related conditions including mTBI, PTSD, and depression. The differing performance patterns observed between the clinical tasks and the more complex experimental tasks support that researchers and clinicians should use tests that sufficiently tax verbal working memory and executive function when evaluating the subtle, higher-order cognitive deficits associated with mTBI and depression.

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Date Created
  • 2017

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Traumatic brain injury induces rapid enhancement of cortical excitability in juvenile rats

Description

Following a traumatic brain injury (TBI) 5-50% of patients will develop post traumatic epilepsy (PTE). Pediatric patients are most susceptible with the highest incidence of PTE. Currently, we

Following a traumatic brain injury (TBI) 5-50% of patients will develop post traumatic epilepsy (PTE). Pediatric patients are most susceptible with the highest incidence of PTE. Currently, we cannot prevent the development of PTE and knowledge of basic mechanisms are unknown. This has led to several shortcomings to the treatment of PTE, one of which is the use of anticonvulsant medication to the population of TBI patients that are not likely to develop PTE. The complication of identifying the two populations has been hindered by the ability to find a marker to the pathogenesis of PTE. The central hypothesis of this dissertation is that following TBI, the cortex undergoes distinct cellular and synaptic reorganization that facilitates cortical excitability and promotes seizure development. Chapter 2 of this dissertation details excitatory and inhibitory changes in the rat cortex after severe TBI. This dissertation aims to identify cortical changes to a single cell level after severe TBI using whole cell patch clamp and electroencephalogram electrophysiology. The work of this dissertation concluded that excitatory and inhibitory synaptic activity in cortical controlled impact (CCI) animals showed the development of distinct burst discharges that were not present in control animals. The results suggest that CCI induces early "silent" seizures that are detectable on EEG and correlate with changes to the synaptic excitability in the cortex. The synaptic changes and development of burst discharges may play an important role in synchronizing the network and promoting the development of PTE.

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Created

Date Created
  • 2014

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Targeting astrogliosis: isolation and characterization of astrocyte specific single chain antibody fragments

Description

Specificity and affinity towards a given ligand/epitope limit target-specific delivery. Companies can spend between $500 million to $2 billion attempting to discover a new drug or therapy; a significant portion

Specificity and affinity towards a given ligand/epitope limit target-specific delivery. Companies can spend between $500 million to $2 billion attempting to discover a new drug or therapy; a significant portion of this expense funds high-throughput screening to find the most successful target-specific compound available. A more recent addition to discovering highly specific targets is the application of phage display utilizing single chain variable fragment antibodies (scFv). The aim of this research was to employ phage display to identify pathologies related to traumatic brain injury (TBI), particularly astrogliosis. A unique biopanning method against viable astrocyte cultures activated with TGF-β achieved this aim. Four scFv clones of interest showed varying relative affinities toward astrocytes. One of those four showed the ability to identify reactive astroctyes over basal astrocytes through max signal readings, while another showed a statistical significance in max signal reading toward basal astrocytes. Future studies will include further affinity characterization assays. This work contributes to the development of targeting therapeutics and diagnostics for TBI.

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Created

Date Created
  • 2013

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Repetitive mild traumatic brain injury induces ventriculomegaly and cortical thinning in juvenile rats

Description

Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for 70-90% of all TBI cases,

Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for 70-90% of all TBI cases, yet its neuropathophysiology is still poorly understood. While a single mTBI injury can lead to persistent deficits, repeat injuries increase the severity and duration of both acute symptoms and long term deficits. In this study, to model pediatric repetitive mTBI (rmTBI) we subjected unrestrained juvenile animals (post-natal day 20) to repeat weight drop impact. Animals were anesthetized and subjected to sham or rmTBI once per day for 5 days. At 14 days post injury (PID), magnetic resonance imaging (MRI) revealed that rmTBI animals displayed marked cortical atrophy and ventriculomegaly. Specifically, the thickness of the cortex was reduced up to 46% beneath and the ventricles increased up to 970% beneath the impact zone. Immunostaining with the neuron specific marker NeuN revealed an overall loss of neurons within the motor cortex but no change in neuronal density. Examination of intrinsic and synaptic properties of layer II/III pyramidal neurons revealed no significant difference between sham and rmTBI animals at rest or under convulsant challenge with the potassium channel blocker, 4-Aminophyridine. Overall, our findings indicate that the neuropathological changes reported after pediatric rmTBI can be effectively modeled by repeat weight drop in juvenile animals. Developing a better understanding of how rmTBI alters the pediatric brain may help improve patient care and direct "return to game" decision making in adolescents.

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Created

Date Created
  • 2014

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Finite element modeling of human brain response to football helmet impacts

Description

The football helmet is a device used to help mitigate the occurrence of impact-related traumatic (TBI) and minor traumatic brain injuries (mTBI) in the game of American football. The current

The football helmet is a device used to help mitigate the occurrence of impact-related traumatic (TBI) and minor traumatic brain injuries (mTBI) in the game of American football. The current design methodology of using a hard shell with an energy absorbing liner may be adequate for minimizing TBI, however it has had less effect in minimizing mTBI. The latest research in brain injury mechanisms has established that the current design methodology has produced a helmet to reduce linear acceleration of the head. However, angular accelerations also have an adverse effect on the brain response, and must be investigated as a contributor of brain injury.

To help better understand how the football helmet design features effect the brain response during impact, this research develops a validated football helmet model and couples it with a full LS-DYNA human body model developed by the Global Human Body Modeling Consortium (v4.1.1). The human body model is a conglomeration of several validated models of different sections of the body. Of particular interest for this research is the Wayne State University Head Injury Model for modeling the brain. These human body models were validated using a combination of cadaveric and animal studies. In this study, the football helmet was validated by laboratory testing using drop tests on the crown of the helmet. By coupling the two models into one finite element model, the brain response to impact loads caused by helmet design features can be investigated. In the present research, LS-DYNA is used to study a helmet crown impact with a rigid steel plate so as to obtain the strain-rate, strain, and stress experienced in the corpus callosum, midbrain, and brain stem as these anatomical regions are areas of concern with respect to mTBI.

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Agent

Created

Date Created
  • 2014

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Novel protein delivery platforms to modulate SDF-1a/CXCR4 signaling in the adult cortex

Description

Stromal cell-derived factor-1α (SDF-1α) and its key receptor, CXCR4 are ubiquitously expressed in systems across the body (e.g. liver, skin, lung, etc.). This signaling axis regulates a myriad of physiological

Stromal cell-derived factor-1α (SDF-1α) and its key receptor, CXCR4 are ubiquitously expressed in systems across the body (e.g. liver, skin, lung, etc.). This signaling axis regulates a myriad of physiological processes that range from maintaining of organ homeostasis in adults to, chemotaxis of stem/progenitor and immune cell types after injury. Given its potential role as a therapeutic target for diverse applications, surprisingly little is known about how SDF-1α mediated signaling propagates through native tissues. This limitation ultimately constrains rational design of interventional biomaterials that aim to target the SDF-1α/CXCR4 signaling axis. One application of particular interest is traumatic brain injury (TBI) for which, there are currently no means of targeting the underlying biochemical pathology to improve prognosis.

Growing evidence suggests a relationship between SDF-1α/CXCR4 signaling and endogenous neural progenitor/stem cells (NPSC)-mediated regeneration after neural injury. Long-term modulation of the SDF-1α/CXCR4 signaling axis is thus hypothesized as a possible avenue for harnessing and amplifying endogenous regenerative mechanisms after TBI. In order to understand how the SDF-1α/CXCR4 signaling can be modulated in vivo, we first developed and characterized a sustained protein delivery platform in vitro. We were the first, to our knowledge, to demonstrate that protein release profiles from poly(D,L,-lactic-co-glycolic) acid (PLGA) particles can be tuned independent of particle fabrication parameters via centrifugal fractioning. This process of physically separating the particles altered the average diameter of a particle population, which is in turn was correlated to critical release characteristics. Secondly, we demonstrated sustained release of SDF-1α from PLGA/fibrin composites (particles embedded in fibrin) with tunable burst release as a function of fibrin concentration. Finally, we contrasted the spatiotemporal localization of endogenous SDF-1α and CXCR4 expression in response to either bolus or sustained release of exogenous SDF-1α. Sustained release of exogenous SDF-1α induced spatially diffuse endogenous SDF-1/CXCR4 expression relative to bolus SDF-1 administration; however, the observed effects were transient in both cases, persisting only to a maximum of 3 days post injection. These studies will inform future systematic evaluations of strategies that exploit SDF-1α/CXCR4 signaling for diverse applications.

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Date Created
  • 2016

Severe traumatic brain injury induces cortical remodeling in the pediatric inhibitory network

Description

Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. When TBI occurs in children it often results in severe cognitive and behavioral deficits.

Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. When TBI occurs in children it often results in severe cognitive and behavioral deficits. Post-injury, the pediatric brain may be sensitive to the effects of TBI while undergoing a number of age-dependent physiological and neurobiological changes. Due to the nature of the developing cortex, it is important to understand how a pediatric brain recovers from a severe TBI (sTBI) compared to an adult. Investigating major cortical and cellular changes after sTBI in a pediatric model can elucidate why pediatrics go on to suffer more neurological damage than an adult after head trauma. To model pediatric sTBI, I use controlled cortical impact (CCI) in juvenile mice (P22). First, I show that by 14 days after injury, animals begin to show recurrent, non-injury induced, electrographic seizures. Also, using whole-cell patch clamp, layer V pyramidal neurons in the peri-injury area show no changes except single-cell excitatory and inhibitory synaptic bursts. These results demonstrate that CCI induces epileptiform activity and distinct synaptic bursting within 14 days of injury without altering the intrinsic properties of layer V pyramidal neurons. Second, I characterized changes to the cortical inhibitory network and how fast-spiking (FS) interneurons in the peri-injury region function after CCI. I found that there is no loss of interneurons in the injury zone, but a 70% loss of parvalbumin immunoreactivity (PV-IR). FS neurons received less inhibitory input and greater excitatory input. Finally, I show that the cortical interneuron network is also affected in the contralateral motor cortex. The contralateral motor cortex shows a loss of interneurons and loss of PV-IR. Contralateral FS neurons in the motor cortex synaptically showed greater excitatory input and less inhibitory input 14 days after injury. In summary, this work demonstrates that by 14 days after injury, the pediatric cortex develops epileptiform activity likely due to cortical inhibitory network dysfunction. These findings provide novel insight into how pediatric cortical networks function in the injured brain and suggest potential circuit level mechanisms that may contribute to neurological disorders as a result of TBI.

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Agent

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Date Created
  • 2015

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Modulating chemokine receptor expression in neural stem cell transplants to promote migration after traumatic brain injury

Description

Traumatic brain injury (TBI) is a significant public health concern in the U.S., where approximately 1.7 million Americans sustain a TBI annually, an estimated 52,000 of which lead to death.

Traumatic brain injury (TBI) is a significant public health concern in the U.S., where approximately 1.7 million Americans sustain a TBI annually, an estimated 52,000 of which lead to death. Almost half (43%) of all TBI patients report experiencing long-term cognitive and/or motor dysfunction. These long-term deficits are largely due to the expansive biochemical injury that underlies the mechanical injury traditionally associated with TBI. Despite this, there are currently no clinically available therapies that directly address these underlying pathologies. Preclinical studies have looked at stem cell transplantation as a means to mitigate the effects of the biochemical injury with moderate success; however, transplants suffer very low retention and engraftment rates (2-4%). Therefore, transplants need better tools to dynamically respond to the injury microenvironment.

One approach to develop new tools for stem cell transplants may be to look towards the endogenous repair response for inspiration. Specifically, activated cell types surrounding the injury secrete the chemokine stromal cell-derived factor-1α (SDF-1α), which has been shown to play a critical role in recruiting endogenous neural progenitor/stem cells (NPSCs) to the site of injury. Therefore, it was hypothesized that improving NPSC response to SDF-1α may be a viable mechanism for improving NPSC transplant retention and migration into the surrounding host tissue. To this end, work presented here has 1. identified critical extracellular signals that mediate the NPSC response to SDF-1α, 2. incorporated these findings into the development of a transplantation platform that increases NPSC responsiveness to SDF-1α and 3. observed increased NPSC responsiveness to local exogenous SDF-1α signaling following transplantation within our novel system. Future work will include studies investigating NSPC response to endogenous, injury-induced SDF-1α and the application of this work to understanding differences between stem cell sources and their implications in cell therapies.

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Agent

Created

Date Created
  • 2015