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- Creators: Barrett, The Honors College
- Creators: Stabenfeldt, Sarah
- Status: Published
Description
The objective of this small animal pre-clinical research project was to study quantitatively the long-term micro- and macro- structural brain changes employing multiparametric MRI (Magnetic Resonance Imaging) techniques. Two separate projects make up the basis of this thesis. The first part focuses on obtaining prognostic information at early stages in the case of Traumatic Brain Injury (TBI) in rat animal model using imaging data acquired at 24-hours and 7-days post injury. The obtained parametric T2 and diffusion values from DTI (Diffusion Tensor Imaging) showed significant deviations in the signal intensities from the control and were potentially useful as an early indicator of the severity of post-traumatic injury damage. DTI was especially critical in distinguishing between the cytotoxic and vasogenic edema and in identification of injury regions resolving to normal control values by day-7. These results indicate the potential of quantitative MRI as a clinical marker in predicting prognosis following TBI. The second part of this thesis focuses on studying the effect of novel therapeutic strategies employing dendritic cell (DC) based vaccinations in mice glioma model. The treatment cohorts included comparing a single dose of Azacytidine drug vs. mice getting three doses of drug per week. Another cohort was used as an untreated control group. The MRI results did not show any significant changes in between the two treated cohorts with no reduction in tumor volumes compared to the control group. The future studies would be focused on issues regarding the optimal dose for the application of DC vaccine. Together, the quantitative MRI plays an important role in the prognosis and diagnosis of the above mentioned pathologies, providing essential information about the anatomical location, micro-structural tissue environment, lesion volume and treatment response.
ContributorsAnnaldas, Bharat (Author) / Kodibagkar, Vikram (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Bhardwaj, Ratan (Committee member) / Arizona State University (Publisher)
Created2014
Description
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.
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.
ContributorsHarrison, Jordan L (Author) / Lifshitz, Jonathan (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Willyerd, Frederick A (Committee member) / Pirrotte, Patrick (Committee member) / Arizona State University (Publisher)
Created2017
Description
Abstract White matter thickness correlates with various mental illness. Commissure white matter tracts are responsible for interconnecting the same cortical area in both hemispheres. Injury to the brain can result in thinning and shrinkage even collapsing and detachment of the white matter tracts' myelin sheaths. Injury can affect cognitive function and time points are essential for therapeutic intervention. Research is beginning to identify gradual long-term neurodegenerative effects. With the advancement of brain imaging technology, we know that Wallerian degeneration has a significant negative impact on the white matter tracts throughout the brain (Johnson, Stewart, & Smith, 2013). If major tracts become injured like, the corpus callosum, then it can affect interhemispheric communication. Once myelin is damaged the axon becomes vulnerable, and the mechanisms of nerve recovery are not well known. Myelin sheath recovery has been studied in hopes to proliferate the oligodendrocytes that make up for the atrophied myelin. Neurotoxic chemicals released at activation of macrophages which hinders the brains ability to proliferate myelin protein needed for myelin differentiation adequately. In the central nervous system myelin has mechanisms to recover. Neurogenesis is a naturally occurring recovery mechanism seen after brain injury. Understanding the time points in which brain recovery occurs is important for treatment of diffuse injuries that cannot be identified through some imaging techniques. To better understand critical timepoints of natural recovery after brain injury can allow further investigation for early intervention to promote adequate recovery.
ContributorsLiptow, Kristen Ashley (Author) / Neisewander, Janet (Thesis director) / Law, L. Matthew (Committee member) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
In this quantitative research paper, we explored the correlation between the six dimensions of motivation as part of the Self-Determination Theory spectrum and physical activity. In addition, our aim was to also see if Transcranial Direct Current Stimulation (tDCS) paired with exercise as an intervention would affect motivation to exercise over time.
ContributorsPankoff, Mia (Author) / Quezada, Gabrielle (Co-author) / Katsanos, Christos (Thesis director) / Shaffer, Zachary (Committee member) / Ruiz Tejada, Anaissa (Committee member) / Barrett, The Honors College (Contributor) / Edson College of Nursing and Health Innovation (Contributor)
Created2021-12
Description
In this quantitative research paper, we explored the correlation between the six dimensions of motivation as part of the Self-Determination Theory spectrum and physical activity. In addition, our aim was to also see if Transcranial Direct Current Stimulation (tDCS) paired with exercise as an intervention would affect motivation to exercise over time.
ContributorsQuezada, Gabrielle (Author) / Pankoff, Mia (Co-author) / Katsanos, Christos (Thesis director) / Shaffer, Zachary (Committee member) / Ruiz Tejada, Anaissa (Committee member) / Barrett, The Honors College (Contributor) / Edson College of Nursing and Health Innovation (Contributor) / College of Integrative Sciences and Arts (Contributor)
Created2021-12
Description
For my thesis, I conducted a study on a healthy pediatric cohort to investigate how DNA methylation of genes related to myelin may predict total white matter volume in a healthy pediatric cohort. The relatively new field of neuroimaging epigenetics investigates how methylation of genes in peripheral tissue samples is related to certain structural or functional features of the brain, as measured by neuroimaging data. Research has already demonstrated that methylation of genes in peripheral tissues is related to a variety of brain disorders. We hypothesized that methylation of myelin-related genes as measured in saliva samples would predict total white matter volume in a healthy pediatric cohort. After processing DNA methylation data from saliva samples from participants, multiple linear regressions were ran to determine if DNA methylation of myelin related genes was related to total white matter volume, as measured by data from structural MRIs. Results showed that these genes, which included MOG, MBP, and MYRF, significantly predicted total white matter volume. Two genes that were significant in our results have been previously shown to produce proteins that are essential to the structure of myelin.
ContributorsSpencer, Sophie (Author) / Lewis, Candace (Thesis director) / Braden, Blair (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / College of Integrative Sciences and Arts (Contributor)
Created2023-05
Description
Glioblastoma Multiforme is a prevalent and aggressive brain tumor. It has an average 5-year survival rate of 6% and average survival time of 14 months. Using patient-specific MRI data from the Barrow Neurological Institute, this thesis investigates the impact of parameter manipulation on reaction-diffusion models for predicting and simulating glioblastoma growth. The study aims to explore key factors influencing tumor morphology and to contribute to enhancing prediction techniques for treatment.
ContributorsShayegan, Tara (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution & Social Change (Contributor)
Created2024-05
Description
Previous research has showed that auditory modulation may be affected by pure tone
stimuli played prior to the onset of speech production. In this experiment, we are examining the
specificity of the auditory stimulus by implementing congruent and incongruent speech sounds in
addition to non-speech sound. Electroencephalography (EEG) data was recorded for eleven adult
subjects in both speaking (speech planning) and silent reading (no speech planning) conditions.
Data analysis was accomplished manually as well as via generation of a MATLAB code to
combine data sets and calculate auditory modulation (suppression). Results of the P200
modulation showed that modulation was larger for incongruent stimuli than congruent stimuli.
However, this was not the case for the N100 modulation. The data for pure tone could not be
analyzed because the intensity of this stimulus was substantially lower than that of the speech
stimuli. Overall, the results indicated that the P200 component plays a significant role in
processing stimuli and determining the relevance of stimuli; this result is consistent with role of
P200 component in high-level analysis of speech and perceptual processing. This experiment is
ongoing, and we hope to obtain data from more subjects to support the current findings.
stimuli played prior to the onset of speech production. In this experiment, we are examining the
specificity of the auditory stimulus by implementing congruent and incongruent speech sounds in
addition to non-speech sound. Electroencephalography (EEG) data was recorded for eleven adult
subjects in both speaking (speech planning) and silent reading (no speech planning) conditions.
Data analysis was accomplished manually as well as via generation of a MATLAB code to
combine data sets and calculate auditory modulation (suppression). Results of the P200
modulation showed that modulation was larger for incongruent stimuli than congruent stimuli.
However, this was not the case for the N100 modulation. The data for pure tone could not be
analyzed because the intensity of this stimulus was substantially lower than that of the speech
stimuli. Overall, the results indicated that the P200 component plays a significant role in
processing stimuli and determining the relevance of stimuli; this result is consistent with role of
P200 component in high-level analysis of speech and perceptual processing. This experiment is
ongoing, and we hope to obtain data from more subjects to support the current findings.
ContributorsTaylor, Megan Kathleen (Author) / Daliri, Ayoub (Thesis director) / Liss, Julie (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The locus coeruleus-norepinephrine system (LC-NE) has been argued to play a vital role in task engagement and attention control by the adaptive gain theory (Aston-Jones & Cohen, 2005). One of the central claims of this theory is that tonic LC activity exhibits a quadratic relationship with task performance. Pupil dynamics have been correlated to LC-NE activity via primate intracranial recordings in ways that provide evidence for the adaptive gain theory. Due to the small size and location of the LC, less is known about LC functioning in humans, leading to a desire to find valid, noninvasive psychophysiological proxies to study this structure. In this paper we performed a replication of Murphy, Robertson, Balsters, & O’Connell (2011) to gather evidence on whether pupil fluctuations and the P3 event-related potential are viable markers for measuring tonic and phasic LC-NE activity in humans. A sample of 33 subjects from the Arizona State University human subjects pool provided usable electroencephalogram and pupillometry data collected during an auditory oddball task. Our analyses largely correspond with those found in Murphy et al. (2011) showing some evidence that pupillometry and P3 can be utilized when studying the LC. Moving forward we will reproduce the full set of analyses from Murphy et al. (2011) with our dataset.
ContributorsStrayer, Deanna L. (Author) / Brewer, Gene (Thesis director) / Robison, Matthew (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Recent studies in traumatic brain injury (TBI) have found a temporal window where therapeutics on the nanometer scale can cross the blood-brain barrier and enter the parenchyma. Developing protein-based therapeutics is attractive for a number of reasons, yet, the production pipeline for high yield and consistent bioactive recombinant proteins remains a major obstacle. Previous studies for recombinant protein production has utilized gram-negative hosts such as Escherichia coli (E. coli) due to its well-established genetics and fast growth for recombinant protein production. However, using gram-negative hosts require lysis that calls for additional optimization and also introduces endotoxins and proteases that contribute to protein degradation. This project directly addressed this issue and evaluated the potential to use a gram-positive host such as Brevibacillus choshinensis (Brevi) which does not require lysis as the proteins are expressed directly into the supernatant. This host was utilized to produce variants of Stock 11 (S11) protein as a proof-of-concept towards this methodology. Variants of S11 were synthesized using different restriction enzymes which will alter the location of protein tags that may affect production or purification. Factors such as incubation time, incubation temperature, and media were optimized for each variant of S11 using a robust design of experiments. All variants of S11 were grown using optimized parameters prior to purification via affinity chromatography. Results showed the efficiency of using Brevi as a potential host for domain antibody production in the Stabenfeldt lab. Future aims will focus on troubleshooting the purification process to optimize the protein production pipeline.
ContributorsEmbrador, Glenna Bea Rebano (Author) / Stabenfeldt, Sarah (Thesis director) / Plaisier, Christopher (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05