Matching Items (6)
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- Genre: Masters Thesis
- Creators: Arizona State University
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 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.
ContributorsMarsh, William (Author) / Stabenfeldt, Sarah (Thesis advisor) / Caplan, Michael (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2013
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 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.
ContributorsNichols, Joshua (Author) / Anderson, Trent (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Newbern, Jason (Committee member) / Arizona State University (Publisher)
Created2014
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 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.
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.
ContributorsDarling, Timothy (Author) / Rajan, Subramaniam D. (Thesis advisor) / Muthuswamy, Jitendran (Thesis advisor) / Oswald, Jay (Committee member) / Mignolet, Marc (Committee member) / Arizona State University (Publisher)
Created2014
Description
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.
ContributorsBrown, Cassie Anne (Author) / Wright, Heather H (Thesis advisor) / Stats-Caldwell, Denise (Committee member) / Ingram, Kelly (Committee member) / Arizona State University (Publisher)
Created2011
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 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.
ContributorsTobin, Edward (Author) / Iasemidis, Leonidas (Thesis advisor) / Tsakalis, Konstantinos (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2012
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, 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.
ContributorsGoddeyne, Corey (Author) / Anderson, Trent (Thesis advisor) / Smith, Brian (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2014