Nervous System Diseases Commons^™

Parkinson’S Disease Phenotype Stratification Using Multiple Correspondence Analysis, Kelly Astudillo

Dissertations, Theses, and Capstone Projects

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, with over 12 million people projected to be affected by 2040 (Dorsey et al., 2018). Deep phenotyping and stratification can provide useful information regarding PD pathogenesis and can aid in the  development of disease modifying therapies that aim to delay the progression or prevent the onset of neurodegeneration (Blandini et al., 2019; Smith & Schapira, 2022). Utilizing multivariate methods such as multiple correspondence analysis (MCA) permits for the simultaneous analysis of distinct data modalities. To the best of our knowledge, MCA has not been previously used to explore phenotype patterns …

A Predictive Coding Account Of Spatial Working Memory Following Prophylactic Levetiracetam Administration Prior To Traumatic Brain Injury, Omeima Mutwali

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) symptom prevention and remediation is an important area of research that would benefit vulnerable groups, including active-duty and veteran soldiers. These patients can sustain penetrative forces in fields of combat or in training, which result in focal lesions that trigger inflammatory and degenerative processes in the brain. Both primary and secondary injuries are associated with changes to cognition, behavior and affective state. This disease poses increased risk of epileptogenesis, as well. Given these outcomes, prior research has evaluated levetiracetam (LEV) as a prophylactic treatment for seizures, cognitive deficits and negative emotionality. LEV acts as a presynaptic …

Cognitive Reserve In Individuals With Frontotemporal Dementia And Primary Progressive Aphasia, Lauren A. Grebe

Dissertations, Theses, and Capstone Projects

Cognitive reserve refers to the brain’s ability to efficiently adapt in the presence of neuropathological disease. This is an active process influenced by individual differences (e.g., genetics) and lifetime experiences (e.g., education, occupation, leisure) (Cabeza et al., 2018; Stern et al., 2020). The cognitive reserve theory has recently been investigated in individuals with frontotemporal dementia (FTD), which refers to various disorders leading to frontotemporal neurodegenerative decline (Young et al., 2018); e.g., behavioral variant of FTD (bvFTD) and variants of Primary Progressive Aphasia (PPA): semantic (svPPA), nonfluent/agrammatic (nfvPPA), and logopenic (lvPPA). However, a clear consensus on the relationship among cognitive reserve, …

Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska

Student Theses and Dissertations

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …

Machine Learning Classification Of Traumatic Brain Injury Patients Versus Healthy Controls Using Arterial Spin Labeled Perfusion Mri, Vanessa I. Grass

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide, yet accurate in vivo detection of TBI neuropathology remains challenging due to complexities in the structural and functional changes observed post-injury as well as limitations in conventional neuroimaging modalities. Although advanced neuroimaging techniques such as arterial spin labeling (ASL) can noninvasively assess cerebral blood flow (CBF) changes observed post-injury, this technique is underutilized in TBI research partly due to the low signal-to-noise-ratio (SNR) inherent in ASL imaging. The aim of the current study is to examine the use of machine learning, specifically a Support …

Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich

Student Theses and Dissertations

Although non-essential, glycine plays an important role in major metabolic reactions and is most known for its anti-inflammatory effects. An accumulation of contemporary research has shown that glycine is able to stabilize membrane potential using glycine receptors at the cellular level and to protect mitochondrial function directly, whether it is from inflammation, heavy metal poisoning, or ischemia-induced neuroinflammation. In this research, the existence of a hypothetical mitochondrial glycine receptor is examined. Immunofluorescence imaging was used to examine the presence of the glycine receptor subunits alpha 1 and alpha 2 in both non- differentiated and differentiated neuroblastoma cell lines. The preliminary …

Criterion Validity Of The Ohio State University Traumatic Brain Injury Identification Method In A Criminal Justice Sample, Sarah M. Monaghan

Student Theses

The purpose of the current study was to determine the clinical utility of the Ohio State University Traumatic Brain Injury Identification Method (OSU-TBI-ID) in a criminal justice sample, by evaluating the criterion-related validity of this instrument. It was hypothesized that this tool could differentiate between incarcerated individuals with or without a history of Traumatic Brain Injury (TBI) on measures evaluating important TBI-related sequalae. The sample consisted of 95 incarcerated men detained at a private correctional facility in a Mid-Atlantic state. Measures used in this study to evaluate executive functioning difficulties, psychiatric difficulties, substance use problems, institutional misconduct and recidivism were …

Allogeneic Bone Marrow–Derived Mesenchymal Stem Cell Safety In Idiopathic Parkinson’S Disease, Timothy M. Ellmore

Publications and Research

Background Neuroinflammation plays a key role in PD pathogenesis, and allogeneic bone marrow–derived mesenchymal stem cells can be used as an immunomodulatory therapy. Objective The objective of this study was to prove the safety and tolerability of intravenous allogeneic bone marrow–derived mesenchymal stem cells in PD patients. Methods This was a 12‐month single‐center open‐label dose‐escalation phase 1 study of 20 subjects with mild/moderate PD assigned to a single intravenous infusion of 1 of 4 doses: 1, 3, 6, or 10 × 106 allogeneic bone marrow–derived mesenchymal stem cells/kg, evaluated 3, 12, 24, and 52 weeks postinfusion. Primary outcome safety measures …

Plasma Proteins That May Cause Parkinson’S Disease And Multiple Sclerosis: A Mendelian Randomization Study, Brigid A. Staley

Dissertations and Theses

Multiple sclerosis (MS) and Parkinson’s disease (PD) are progressively disabling neurologic disorders that profoundly affect quality of life and shorten life expectancy. There is no cure for either disease, and current treatments only alleviate symptoms and may cause serious side effects. The causes of MS and PD are not well understood. Previous epidemiologic studies have documented numerous environmental risk factors for both diseases. However, these studies are inherently prone to bias from confounding which may generate spurious results. The lack of unbiased evidence on environmental causes of MS and PD has been a critical barrier to fully understanding their pathophysiology. …

A Neural Mechanism For Capnotaxis In The Naked Mole-Rat, Michael Zions

Dissertations, Theses, and Capstone Projects

A Neural Mechanism for Capnotaxis in the Naked Mole-Rat

The Naked Mole-Rat (NM-R) is a small hairless rodent that has thrived underground in the Horn of Africa for the past 40 million years. It was first discovered in 1847, but has only been maintained in captivity and studied as a laboratory animal over the past 40 years. To date, more than 400 scientific papers have been published on this species. This is relatively few compared to established lab animals like rats and mice, but those papers contain a trove of information that has changed our understanding of the constraints of …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}

Characterization Of Extracellular Vesicles From Human Diabetic Retinopathy Retinal Tissue In Vitro And From Urine Of Human Patients With Diabetic Retinopathy, Jason Mighty

Dissertations, Theses, and Capstone Projects

Diabetic Retinopathy (DR) is a neurovascular complication associated with diabetes mellitus that affects approximately 120 million people worldwide and its prevalence is expected to reach 190 million by 2030. DR diagnosis is accomplished with fundus ophthalmoscopy often when retinal damage and vision loss have already occurred. A group of biomarker being explored for early detection of diseases are extracellular vesicles (EVs), which are nanometer diameter lipid enclosed vesicles, released from all cell types and containing genetic cargo reflective of releasing cell state. EV biomarkers are currently being explored to help monitor disease predisposition, pathogenesis and response to treatment. While an …

Body Mass Index In Multiple Sclerosis Modulates Ceramide-Induced Dna Methylation And Disease Course, Kamilah Castro, Achilles Ntranos, Mario Amatruda, Maria Petracca, Peter Kosa, Emily Y. Chen, Johannes Morstein, Dirk Trauner, Corey T. Watson, Michael A. Kiebish, Bibiana Bielekova, Matilde Inglese, Ilana Katz Sand, Patricia Casaccia

Advanced Science Research Center

Background: Multiple Sclerosis (MS) results from genetic predisposition and environmental variables, including elevated Body Mass Index (BMI) in early life. This study addresses the effect of BMI on the epigenome of monocytes and disease course in MS.

Methods: Fifty-four therapy-naive Relapsing Remitting (RR) MS patients with high and normal BMI received clinical and MRI evaluation. Blood samples were immunophenotyped, and processed for unbiased plasma lipidomic profiling and genome-wide DNA methylation analysis of circulating monocytes. The main findings at baseline were validated in an independent cohort of 91 therapy-naïve RRMS patients. Disease course was evaluated by a two-year longitudinal follow up …

The Master Synaptic Regulator: Activity Regulated Cytoskeleton Associated Protein, Arc, In Normal Aging And Diseases With Cognitive Impairment, Amber Khan

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with complex underlying pathogenic mechanisms. Epidemiological studies have forecasted that in the next 3 decades, the number of AD cases will rise to epidemic proportions with enormous medical, emotional and financial burdens impacting individuals affected and society. Among many risk factors for AD, advancing age is clearly essential and necessary. Revelation of molecular changes in synaptic activities leading to the prodromal, mild cognitive impairment (MCI) stage may help illuminate the course of pathogenic progression and its cause-effect relationship with various targets thereby enabling target-driven disease-modifying therapeutic agents for AD.

Activity-regulated cytoskeleton-associated (Arc) …

Green Tea Extract, Epigallocatechin Gallate, Protect Against Methamphetamine-Induced Striatal Neurotoxicity In Mice, Allen L. Pan

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) is a strong psychostimulant and its exposure can lead to serious neurological complications. METH-induced neuronal injury is the result of a complex interplay of different factors including dopamine (DA) overflow, oxidative stress and neuroinflammation. Although the mechanisms of METH-induced neurotoxicity have been extensively studied, there is still no effective therapeutic treatment. Therefore, it is essential to study potential drug candidates that can treat METH-induced neurotoxicity. Green tea extract, epigallocatechin gallate (EGCG), has emerged as a neuroprotective agent that can protect against several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Recently, our lab has shown that EGCG prevents …

Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval

Dissertations, Theses, and Capstone Projects

The serotonergic system has been the major candidate in the pathophysiology of mood related disorders such as anxiety and major depressive disorder (MDD). Unfortunately, current antidepressant drugs are ineffective in 50% of the population and require chronic administration for a period of 3-6 weeks before the onset of therapeutic response. 5-HT4 receptor (5-HT₄R) agonists have emerged as potential candidates for fast antidepressant action, since an antidepressant response can be achieved after 3 days of pharmacological administration in rodents.

This dissertation aims to investigate the role of casein kinase 2 (CK2) as a regulator of 5-HT₄R expression …

Assistive Utensil: A Spork For Hand Tremors And Spatial Awareness, Ana Font Hernandez, Jacob Kabariti, Troy Taylor

Publications and Research

In this poster, we present a 3D printed solution for hand tremors and special awareness. Our spork is an assistive device designed and 3D printed for patients suffering from scleroderma, systemic sclerosis, Parkinson's, multiple sclerosis, drug withdrawal, etc. The scale-based handle will act as a counterweight to offset the contents on the other end and reduce shakiness. The larger grip allows an easy and comfortable hold. The product will be 3D printed for a customizable fit and at an affordable price. Lastly, the product will include a haptic feedback sensor to assist the visually impaired in locating food contents on …

Multiple Sclerosis Is Not A Disease Of The Immune System, Angelique Corthals

Publications and Research

Multiple sclerosis is a complex neurodegenerative disease, thought to arise through autoimmunity against antigens of the central nervous system. The autoimmunity hypothesis fails to explain why genetic and environmental risk factors linked to the disease in one population tend to be unimportant in other populations. Despite great advances in documenting the cell and molecular mechanisms underlying MS pathophysiology, the autoimmunity framework has also been unable to develop a comprehensive explanation of the etiology of the disease. I propose a new framework for understanding MS as a dysfunction of the metabolism of lipids. Specifically, the homeostasis of lipid metabolism collapses during …

Impact Of Insurance Status On Migraine Care In The United States, Andrew Wilper, Steffie Woolhandler, David U. Himmelstein, Rachel Nardin

Publications and Research

Objective
To determine whether insurance status is associated with differential outpatient treatment of migraine in the United States.

Methods
We analyzed 11 years of data from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (1997–2007), which survey patient visits to doctors’ offices, hospital outpatient departments, and emergency departments (EDs) in the United States. We used logistic regression to determine whether insurance status was associated with the prescription of standard migraine therapy, defined as 1) a triptan or dihydroergotamine and 2) a prophylactic agent.

Results
We identified 6,814 individual patient visits for migraine, representing 68.6 million …