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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Reducing the Societal Costs of Traumatic Brain Injury: Astrocyte-Based Therapeutics and Functional Injury Tolerance of the Living Brain

Kang, Woo Hyeun January 2014 (has links)
Approximately 1.7 million traumatic brain injuries (TBI) occur annually in the United States, with an annual estimated societal cost of at least $76.5 billion. Addressing the growing TBI epidemic will require a multi pronged approach: developing novel treatment strategies and enhancing existing preventative measures. The specific aims of this thesis are: (1) to modulate astrocyte activation as a potential therapeutic strategy post TBI, (2) to determine the relationship between tissue deformation and alterations in electrophysiological function in the living brain, and (3) to investigate underlying mechanisms of functional changes post TBI by utilizing stretchable microelectrode arrays (SMEAs). In response to disease or injury, astrocytes become activated in a process called reactive astrogliosis. Activated astrocytes generate harmful radicals that exacerbate brain damage and can hinder regeneration of damaged neural circuits by secreting neuro developmental inhibitors and glycosaminoglycans (GAGs). Since mechanically-activated astrocytes upregulate GAG production, delivery of GFP-TAT, a mock therapeutic protein conjugated to the cell-penetrating peptide TAT, increased significantly after activation. A TAT-conjugated peptide JNK inhibitor was delivered to activated astrocytes and significantly reduced activation. These results suggest a potentially new, targeted therapeutic utilizing TAT for preventing astrocyte activation with the possibility of limiting off-target, negative side effects. While modulating astrocyte activation is a promising treatment strategy for TBI, effective therapeutic treatments are still lacking. Preventing TBI, by developing more effective safety systems, remains crucial. We determined functional tolerance criteria for the hippocampus and cortex based on alterations in electrophysiological function in response to controlled mechanical stimuli. Organotypic hippocampal and cortical slice cultures were mechanically injured at tissue strains and strain rates relevant to TBI, and changes in electrophysiological function were quantified. Most changes in electrophysiological function were dependent on strain and strain rate in a complex, nonlinear manner. Our results provide functional data that can be incorporated into finite element (FE) models to improve their biofidelity of accident and collision reconstructions. TBI causes alterations in macroscopic function and behavior, which can be characterized by alterations in electrophysiological function in vitro. We utilized a novel in vitro platform for TBI research, the SMEA, to investigate the effects of TBI on pharmacologically induced, long lasting network synchronization in the hippocampus. Mechanical stimulation of organotypic hippocampal slice cultures significantly disrupted this network synchronization 24 hours after injury. Our results suggest that the ability of the hippocampal neuronal network to develop and sustain network synchronization was disrupted after mechanical injury, while also demonstrating the utility of the SMEA for TBI research. Herein, we identified a novel therapeutic strategy for treating the deleterious effects of astrocyte activation post-TBI. We also developed tolerance criteria relating mechanical injury parameters to electrophysiological function, an important step in developing more accurate computational simulations of TBI. Equipping FE models with new information on the functional response of the living brain will enhance their biofidelity, potentially leading to improved safety systems while reducing development costs. Finally, we utilized a novel in vitro TBI research platform, the SMEA, to investigate the effects of TBI on long-lasting network synchronization in the hippocampus. Compared to more labor intensive in vivo approaches, the ability of the SMEA to efficiently test TBI hypotheses within a single organotypic slice culture over extended durations could increase the speed of drug discovery through high-content screening. This multi-pronged approach is necessary to address the growing public health concern of TBI.
2

The experience of dyspraxia in everyday activities : a phenomenological study

Blijlevens, Heleen Unknown Date (has links)
While dyspraxia has been studied from the neuro-anatomical aspects, few studies have explored the experience of adults with dyspraxia in the course of their everyday activities. This study reveals the unique and complex experiences of five adults as they struggle to live with dyspraxia.The research is underpinned by the phenomenological perspective. Participants were filmed performing everyday activities of their choice and were interviewed on their experiences of dyspraxia with everyday activities.The stories and videos reveal the struggle participants have with their unknowing and unwilling bodies, puzzled thinking, unfamiliar surroundings, and unhandy tools. Despite the enormity of their struggles, participants persevere, using individual strategies to overcome obstacles. The findings show that the lived-experience of dyspraxia tends to remain hidden from the person, as well as the clinician. Much of what is taken for granted during everyday activities is shattered in the lives of people with dyspraxia. The automatic, smooth, unconscious way activities are done, tools are handled and the world is experienced is altered. The path to recovery remains unclear as dyspraxia makes itself known one day and not the next. Sheer determination and a hope for the future helps participants carry on with trying to reclaim the person they lost as a result of the dyspraxia.The importance for understanding, by clinicians of the impact of dyspraxia on people's everyday lives cannot be underestimated. Implications for practice are discussed, as these relate to formal definitions of dyspraxia, client-centred practice, as well as diagnosis, assessment, intervention, and education.

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