Matching Items (3)
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- All Subjects: TBI
- Creators: Aftab, Umar Syed
- Creators: Caplan, Michael
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
The increase of Traumatic Brain Injury (TBI) cases in recent war history has increased the urgency of research regarding how veterans are affected by TBIs. The purpose of this study was to evaluate the effects of TBI on speech recognition in noise. The AzBio Sentence Test was completed for signal-to-noise ratios (S/N) from -10 dB to +15 dB for a control group of ten participants and one US military veteran with history of service-connected TBI. All participants had normal hearing sensitivity defined as thresholds of 20 dB or better at frequencies from 250-8000 Hz in addition to having tympanograms within normal limits. Comparison of the data collected on the control group versus the veteran suggested that the veteran performed worse than the majority of the control group on the AzBio Sentence Test. Further research with more participants would be beneficial to our understanding of how veterans with TBI perform on speech recognition tests in the presence of background noise.
ContributorsCorvasce, Erica Marie (Author) / Peterson, Kathleen (Thesis director) / Williams, Erica (Committee member) / Azuma, Tamiko (Committee member) / Barrett, The Honors College (Contributor) / Department of Speech and Hearing Science (Contributor)
Created2015-05
Description
Traumatic Brain Injury (TBI) affects approximately two million people on an annual basis and increases the frequency and onset of Alzheimer’s disease (AD) and other related dementias (ADRDs). Mechanical damage and shearing of neuronal axons are thought to be responsible for producing toxic variants of proteins that contribute to disease pathology. Specifically, the tau, beta amyloid, alpha-synuclein, and TAR-binding DNA Protein-43 (TDP-43) variants contribute to the heterogenous pathology mechanisms of neurodegenerative diseases. The Sierks lab at Arizona State University has aimed to study how these protein variants collectively interact to contribute to pathologies characteristic of AD/ADRDs. This study focuses on the accumulation of toxic oligomeric variants of TDP-43 secondary to TBI. The first aim of this study was to identify the protein variant fingerprint as a function time following experimental diffuse TBI. The second aim was to investigate if toxic variants of TDP-43 were associated with cognitive and motor functional deficits. C57BL/6 mice were subjected to a single or repetitive diffuse TBI via midline fluid percussion injury or a control surgery (sham). Post-injury, mice were evaluated for cognitive performance, sensorimotor function, and depressive-like behavior at 7-, 14-, and 28-days post-injury. Tissue was collected for immunohistochemistry and stained for ADTDP-3, a single chain antibody variable fragment (ScFv) which binds to toxic variants of TDP-43 in amyotrophic lateral sclerosis (ALS) and AD tissue. A one-way analysis of variance (ANOVA) was performed to compare staining intensity across various brain regions. Subsequently, a Pearson correlation was performed to compare behavioral task performance to staining intensity by brain region for each injury group. There were significantly elevated levels of ADTDP3 binding in all regions except for the hippocampus, and there was a significant correlation between the cortex staining intensity vs the cognitive behavior test at 7 days post-injury. There was also a significant correlation between the thalamus staining intensity and sensorimotor test at 7 days post-injury. These findings support the hypothesis that the accumulation of toxic variants of TDP-43 can contribute to neurodegenerative pathology and loss of function. These variants also may contribute to behavioral deficits secondary to diffuse TBI.
ContributorsAftab, Umar Syed (Author) / Sierks, Michael R (Thesis advisor) / Rowe, Rachel K (Thesis advisor) / Newbern, Jason M (Committee member) / Arizona State University (Publisher)
Created2021