Translational Medical Research Commons^™

Diffuse Correlation Spectroscopy Measures Of Cerebral Blood Flow During Graded Hypoxia In Neonatal Piglets, Danielle Shoshany, Shadi Malaeb, Randolph Sinahon, Mert Deniz Polat, Meltem Izzetoglu, Patricia A. Shewokis, Kurtulus Izzetoglu

St. Chris Research Day

No abstract provided.

Modulating The Mtor Pathway Using Inducible Retrogradely Transported Aavs As A Novel Approach To Improve Motor Recovery In Spinal Cord Injury, Christopher Bosse-Joseph

Theses and Dissertations--Medical Sciences

Spinal cord injury poses multiple regeneration barriers, including neuronal-intrinsic and extrinsic factors. Overcoming these barriers has stood as a longstanding challenge in neuroscience. A well-studied mechanism to promote spinal cord regeneration and locomotor recovery is activating the PI3K/mTOR pathway by knocking out phosphatase and tensin homolog protein (PTEN). PTEN knockout (PTEN-KO) studies have traditionally used adeno-associated virus (AAV) viral vectors to improve functional recovery. The use of traditional AAV serotypes to induce PTEN-KO has shown promise to improve functional recovery in rodent models; however, these approaches show significant limitations for translational utility. Firstly, the use of traditional AAV serotypes to …

Shedding Light On Hearing In Coma: Investigating The Applicability Of Functional Near-Infrared Spectroscopy For Assessing Auditory Function And Aiding Prognosis In Patients With Acute Disorders Of Consciousness, Reza Moulavi Ardakani

Electronic Thesis and Dissertation Repository

There is a critical need for a bedside neuroimaging tool to aid in the prediction of functional recovery outcomes for patients with acute disorders of consciousness (DoC) in the early days following severe brain injury. Current neurobehavioral examinations and prognosis tools have limitations in predicting good outcomes, leading to potential mistreatment or premature withdrawal of life support. Functional near-infrared spectroscopy (fNIRS) is a viable candidate for such purposes due to its portability and cost-effectiveness. Auditory processing, viewed as a multi-level and multifaceted brain function, could provide a sensitive and specific marker of residual cognitive function in unresponsive patients. This study …

Social Dominance Alters Stress-Induced Neural Activity And Generates Individual Differences In Stress Vulnerability, Jenna Lee Laymon

Masters Theses

Identifying the physiological and behavioral mechanisms that underlie stress vulnerability is a crucial step toward identifying novel targets for the prevention and treatment of stress-related disorders. Social status is a key environmental factor that contributes to individual variations in stress vulnerability. In particular, achieving a subordinate social status has been shown to produce susceptibility to anxiety-like and depressive-like behavior. In this project, our aim was to identify neural ensembles regulating how dominance status modulated stress-induced changes in avoidant behavior in male and female Syrian hamsters. Using a viral vector that codes for robust activity marker (RAM), we investigated whether stress-induced …

Assessment Of The Interplay Between Regional Β-Amyloid Burden And White Matter Hyperintensities On Cognition And Default Mode Network In Clinically Normal Older Participants, Doaa G. Ali

Theses and Dissertations--Clinical and Translational Science

Objective: Alzheimer’s disease (AD) and subcortical vascular dementia are considered the most common pathologic contributors to dementia in the aging population. Both frequently coexist in over 80% of community dwelling adults with dementia. The neuropathological development of AD arguably begins with β-amyloid (Aβ) deposition in the brain. This series of studies aims to test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in preclinical AD (pAD) (study1). Since mixed dementia is widely recognized as the norm rather than the exception, the second study aimed to explore the …

Contributions Of Asymmetry And Instability To Transfer And Retention Following Locomotor Adaptation, Daniel L. Gregory

Doctoral Dissertations

Gait asymmetry resulting from neurological injury is more costly and less stable than healthy gait. Split-belt treadmills, which drive limbs at different speeds, lead to spatial and temporal gait asymmetries, and perturb walking balance, have been used to study locomotor adaptability and learning related to asymmetry and stability. This knowledge may be leveraged to design more effective rehabilitation protocols. In experiment 1, we asked how constraining stride-rates away from preferred during split-belt walking influences learning revealed in a retention test. We found that constraints to stride rate during asymmetric walking uncovered the capacity to leverage redundant degrees-of-freedom for walking control, …

Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin

Dissertations & Theses (Open Access)

One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test …

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS: Single-cell …

Development Of A Method Using Retrograde Neuronal Tracers To Neuroanatomically Characterize Respiratory Neural Circuitry, Samantha Thomas, Angelo Lepore

Phase 1

Introduction:

Loss of respiratory function is one of the leading causes of death following spinal cord injury (SCI). Existing studies have demonstrated that pre-phrenic interneurons (PPIN’s) can be recruited into the phrenic motor neuron (PhMN) pathway following cervical SCI and may contribute to respiratory recovery, but there is still a lack of information detailing the nature of these changes and the extent they may improve diaphragm function. This project aims to validate a method of utilizing neuronal tracers to further characterize the intact respiratory circuitry.

Methods:

This study was carried out using a rat model. A fluorophore-conjugated retrograde neuronal …

Brainwave Nets: Are Sparse Dynamic Models Susceptible To Brain Manipulation Experimentation?, Diego C. Nascimento, Marco A. Pinto-Orellana, Joao P. Leite, Dylan J. Edwards, Francisco Louzada, Taiza E.G. Santos

Research outputs 2014 to 2021

© Copyright © 2020 Nascimento, Pinto-Orellana, Leite, Edwards, Louzada and Santos. Sparse time series models have shown promise in estimating contemporaneous and ongoing brain connectivity. This paper was motivated by a neuroscience experiment using EEG signals as the outcome of our established interventional protocol, a new method in neurorehabilitation toward developing a treatment for visual verticality disorder in post-stroke patients. To analyze the [complex outcome measure (EEG)] that reflects neural-network functioning and processing in more specific ways regarding traditional analyses, we make a comparison among sparse time series models (classic VAR, GLASSO, TSCGM, and TSCGM-modified with non-linear and iterative optimizations) …

Developing Drug Therapies: Cognitive Damage In Mice Following Brain Radiation, Rachel Yuska

The Journal of Purdue Undergraduate Research

Pediatric brain cancer patients are at a high risk for radiation-induced cognitive impairment due to white matter changes in the brain. Half of six-month radiotherapy survivors develop significant changes in white matter. Previous research has shown that a mouse model can be used to show similar cognitive and behavioral deficits in human patients. The purpose of this work is to evaluate the effectiveness of two drug therapies, Donepezil and 3,3-Diindolylmethane (DIM), that could be used to either protect the brain from radiation injury or cure the cognitive injury and behavioral deficits that result from whole-brain irradiation. This project consisted of …

Electroencephalogram As A Diagnostic Tool In Acquired Brain Injury, Michael Zarra

Senior Theses and Projects

The ability of electroencephalogram (EEG) to be used as a diagnostic device for acquired brain injuries (ABI) has been conceptualized previously. Averaged event-related potentials (ERP) derived from an EEG are suitable as markers of dysfunction however, distinctive properties in the frequency domain have not been established previously. In the present study, we examined pre- existing EEG signal data of healthy adults (HA), mild ABI (mABI), and severe ABI (sABI) human groups. Through Fourier analysis performed in MATLAB, we found that individuals in our sample population (n=80) were able to be categorized into their respective group based on common neuronal activity …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

Translational Modeling Of Non-Invasive Electrical Stimulation, Dennis Quangvinh Truong

Dissertations and Theses

Seminal work in the early 2000’s demonstrated the effect of low amplitude non-invasive electrical stimulation in people using neurophysiological measures (motor evoked potentials, MEPs). Clinical applications of transcranial Direct Current Stimulation (tDCS) have since proliferated, though the mechanisms are not fully understood. Efforts to refine the technique to improve results are on-going as are mechanistic studies both in vivo and in vitro. Volume conduction models are being applied to these areas of research, especially in the design and analysis of clinical montages. However, additional research on the parameterization of models remains.

In this dissertation, Finite Element Method (FEM) models of …

Coupling Of Smoothened To Inhibitory G Proteins Reduces Voltage-Gated K, Lan Cheng, Moza Al-Owais, Manuel Covarrubias, Walter J. Koch, David R. Manning, Chris Peers, Natalia A Riobo-Del Galdo

Department of Biochemistry and Molecular Biology Faculty Papers

SMO (Smoothened), the central transducer of Hedgehog signaling, is coupled to heterotrimeric G_i proteins in many cell types, including cardiomyocytes. In this study, we report that activation of SMO with SHH (Sonic Hedgehog) or a small agonist, purmorphamine, rapidly causes a prolongation of the action potential duration that is sensitive to a SMO inhibitor. In contrast, neither of the SMO agonists prolonged the action potential in cardiomyocytes from transgenic G_iCT/TTA mice, in which G_i signaling is impaired, suggesting that the effect of SMO is mediated by G_i proteins. Investigation of the mechanism underlying the change …

Motor Learning And Adaptation In People With Knee Osteoarthritis And Chronic Pain, Heather Turcotte, Katherine S. Rudolph

Osteopathic Medicine Student Research Posters

Osteoarthritis (OA) affects an estimated 50 million people in the US, and approximately 43% have limitations in daily function due to arthritis pain.3 Individuals with knee osteoarthritis (OA) have heightened sensitization to pain2,5 as well as reduced strength, diminished function and quality of life1 that prompts them to seek care from health care providers. Physical therapists commonly work with patients to improve function and quality of life by helping them learn to move without pain. Unfortunately, chronic pain causes changes to the nervous system that may impact the ability to learn new ways but the extent to which chronic pain …

Carotid Ultrasound Is Not Helpful In Simple Syncope, Nicholus Yee M.D., Shilin Patel M.D., Raymond Gong

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Scott JW, Schwartz AL, Gates JD, Gerhard-Herman M, Havens JM. Choosing wisely for syncope: low-value carotid ultrasound use. J Am Heart Assoc. 2014 Aug 13;3(4). pii: e001063. doi: 10.1161/JAHA.114.001063

Molecular Analyses Of Circadian Gene Variants Reveal Sex-Dependent Links Between Depression And Clocks, S-Q Shi, M. J. White, H. M. Borsetti, Julie S. Pendergast, A. Hida, C. M. Ciarleglio, P. A. De Verteuil, A. G. Cadar, C. Cala, D. G. Mcmahon, R. C. Shelton, S. M. Williams, C. H. Johnson

Biology Faculty Publications

An extensive literature links circadian irregularities and/or sleep abnormalities to mood disorders. Despite the strong genetic component underlying many mood disorders, however, previous genetic associations between circadian clock gene variants and major depressive disorder (MDD) have been weak. We applied a combined molecular/functional and genetic association approach to circadian gene polymorphisms in sex-stratified populations of control subjects and case subjects suffering from MDD. This approach identified significant sex-dependent associations of common variants of the circadian clock genes hClock, hPer3 and hNpas2 with major depression and demonstrated functional effects of these polymorphisms on the expression or activity of the hCLOCK …

Brain Blast 2015 Speakers Poster, Annie Leslie

Brain Blast

Poster from UNE's Brain Blast 2015 listing the expected presenters at this event.*

Brain Blast 2014 Speakers Poster, Annie Leslie

Brain Blast

Poster from UNE's Brain Blast 2014 listing the presenters at this event.

Brain Blast 2014 Poster, Annie Leslie

Brain Blast

Announcement poster for UNE's Brain Blast 2014, a pechakucha-style brain health and safety awareness and learning event.