Nervous System Diseases Commons^™

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

Dissertations & Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly …

The Use Of Current Steering During Subthalamic Deep Brain Stimulation To Alleviate Upper Limb Symptoms Of Parkinson's Disease, Shabna Iftikar Mohideen

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) is an established treatment to alleviate the appendicular motor symptoms of Parkinson's Disease (PD). Current steering during DBS allows the unequal fractionation of current between two electrodes on the lead, resulting in a non-spherical electrical field. It is hypothesized that the way the electrical field is shaped will affect a patient’s upper limb symptom alleviation. Seven PD patients who underwent bilateral STN-DBS were tested over four weeks post-operation. 16 current fractionation settings were tested each week at an amplitude that increased weekly. Optimal setting was defined as the setting that provided the best …

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit

Electronic Thesis and Dissertation Repository

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …

Limbic System Involvement In Absence Seizures, Rukham Ajaz

Electronic Thesis and Dissertation Repository

Absence epilepsy is characterized by brief spells of absent stare and spike wave discharges (SWDs), generally believed to be generated by a thalamocortical network. Our lab showed that hippocampal neuronal firings were synchronous with SWDs in a gamma butyrolactone (GBL) model of absence epilepsy in rats (Arcaro et al., 2016). We hypothesize that, in a GBL model of absence seizures, 30-400 Hz oscillations in the spontaneous local field potentials (LFPs) in the hippocampus and other parts of limbic system (amygdala and nucleus accumbens) are phase modulated by SWDs, and this modulation is mediated through nucleus reuniens of midline thalamus (RE). …

The Brain-Heart Connection: Establishment Of A Novel Rodent Model Of Focal Insular Ischemic Stroke To Examine The Pathophysiology Of Stroke-Induced Heart Injury, Victoria Thorburn

Electronic Thesis and Dissertation Repository

The neurological influence of ischemic stroke in the generation of stroke-induced heart injury (SIHI) has been acknowledged for several years. However, pathophysiological mechanisms remain uncertain. Clinically, it is hypothesized that stroke involving the insular cortex (IC) initiates SIHI, since the IC controls autonomic regulation of cardiovascular function. Yet, given the high prevalence of shared risk factors between ischemic stroke and cardiovascular disorders, mechanistic conclusions from clinical studies are largely speculative. We therefore sought to establish a novel rodent model of focal insular ischemic stroke, used to evaluate chronic outcomes of SIHI. Focal ischemic stroke was induced into the right or …

Changes In The Testes Following Spinal Cord Injury And The Attenuating Effects Of Licofelone, Ryan Fortune

Dissertations & Theses (Open Access)

Spinal cord injury is a devastating disease that researchers have had very limited success in treating. In addition to interrupted innervation, spinal cord injury causes pathologic changes in a multitude of organ systems. Male infertility is one such complication that is particularly devastating because the patient population is predominantly young men. Our lab has previously shown that the blood testis barrier breaks down after spinal cord injury. This dissertation shows the local metabolomic and mRNA changes that spinal cord injury causes within the testes using a Sprague Dawley rat model, including the elevation in eicosanoids, increased oxidative stress, chronically elevated …

Regulations Of Pathogenic Cd4+ T Helper Lymphocytes In Inflammatory Diseases, Handong Zheng

Biomedical Sciences ETDs

In this comprehensive project, three interrelated studies with distinct foci were employed to understand the regulations of specific CD4⁺ T helper cell population in inflammatory diseases.

Pathogenic TH17 cells play an essential role in the initiation and development of both human multiple sclerosis (MS) and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, the underlying mechanism by which the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation remains unclear. In aim 1, we revealed that lumican (Lum), an extracellular matrix (ECM) protein, negatively regulates encephalitic TH17 cell responses. Our findings highlighted a TH17 cell-intrinsic effect of Lum in suppressing …

Evaluating White Matter Changes And Executive Function In Rat Models Of Mediodorsal Thalamic Stroke And Neuroinflammation, Jessica Garabon

Electronic Thesis and Dissertation Repository

Recent literature has supported a relationship between vascular disease and its role in the progression of cognitive impairment. Previous studies have demonstrated that white matter inflammation (WMI) in the brain is a common pathological outcome following stroke. Moreover, WMI has been shown to be the strongest predictor of cognitive decline following stroke. Finally, previous work in our lab has demonstrated, using a rodent model of striatal stroke, that WMI is correlated with post-stroke cognitive impairment. The current study aimed to further investigate the role of WMI in post-stroke cognitive impairment by utilizing a mediodorsal thalamic (MD) stroke model in the …

Role Of The Dorsal Striatum In Learning And Decision Making, Nole M. Hiebert

Electronic Thesis and Dissertation Repository

The striatum, the input region of the basal ganglia, has been shown to mediate many cognitive functions. The striatum itself can be functionally segregated into dorsal (DS) and ventral striatum (VS). For more than 60 years, DS has been reported to mediate stimulus-response learning, though evidence has been accruing pointing to a role in decision making. These literatures have been growing independently and an aim of this thesis was to bridge these two bodies of knowledge. We directly investigated the role of DS in stimulus-response learning versus decision making using functional magnetic resonance imaging (fMRI) in patients with Parkinson’s disease …

Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson

Theses & Dissertations

Multiple cancer populations frequently report cognitive impairment following treatment with chemotherapy agents (“chemo-brain”). Impaired neuropsychological performance is commonly reported in cognitive domains of attention and executive function. Understanding neural mechanisms underlying cognitive impairments is essential to developing prevention and rehabilitation strategies. Brain imaging studies frequently show chemotherapy-related impairments within the attentional control network, which is comprised of a constellation of cortical regions that govern reportedly impaired cognitive functions. In the current dissertation research, I developed a novel electrophysiology battery aimed at recording near-instantaneous neural activity within the attentional control network during cognitive task performance. Cancer patients diagnosed with hematological malignancy …

A Role Of Vitamin B2 In Reducing Amyloid-Beta Toxicity In A Caenorhabditis Elegans Alzheimer’S Disease Model, Muhammad Tukur Ameen

Electronic Theses and Dissertations

Alzheimer’s disease (AD) is associated with amyloid-beta peptide deposition and loss of mitochondrial function. Using a transgenic C. elegans AD worm model expressing amyloid-beta in body wall muscle, we determined that supplementation with either of the forms of vitamin B₂, flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) protected against amyloid-beta mediated paralysis. FMN and FAD were then assayed to determine effects on ATP, oxygen consumption, and reactive oxygen species (ROS) with these compounds not significantly improving any of these mitochondrial bioenergetic functions. Knockdown of the daf-16/FOXO transcriptional regulator or the FAD synthase enzyme completely abrogated the …

The Incidence Rate, Types, And External Causes Of Traumatic Brain Injuries In Parkinson’S Disease Patients In Nebraska 2008-2014, Maher Alsaadi

Capstone Experience

Background: Parkinson’s disease (PD) patients are at higher risk of traumatic brain injury (TBI) due to disease characteristics like tremor, bradykinesia, and impaired balance. Most of the studies that have been done in the United States to investigate the incident rate and causes of TBI among PD patients have mainly focused on falls, while none of these studies have thoroughly addressed all causes of TBI among the PD population or have used a population-based database. Our study aims to investigate the incidence rate, types, and external causes of TBI stratified by age of PD diagnosis using a population-based database from …

Sleep, And Its Relation To Non-Motor Deficits In Patients With Cerebellar Ataxia, Akshata Sonni

Doctoral Dissertations

The cerebellum is a highly connected structure, and its involvement in sleep – which is a dynamic process that is modulated by a complex set of neural systems – can come about through a number of neural pathways. We conducted two studies aimed at furthering our understanding of cerebellar involvement in sleep behavior and physiology, as well as measuring the impact of poor sleep on mood and cognition in patients with cerebellar degeneration. First, by means of an online battery including measures of sleep and neuropsychiatric function, we collected data from 176 patients with cerebellar ataxia. We found strong evidence …

Characterization Of The Roles Of Muscle-Synthesized Brain-Derived Neurotrophic Factor And Presynaptic Tyrosine Receptor Kinase B In Motor Neuron Axonal Transport, Luke A. Vanosdol

All NMU Master's Theses

Brain-derived neurotrophic factor (BDNF) is a small, diffusible protein essential for the development and function of neurons. It is synthesized by many types of tissue, including muscle. BDNF actions are mediated via binding to its receptor, tyrosine receptor kinase B (TrkB). The BDNF-TrkB complex is endocytosed into a specialized vesicle, which induces downstream signaling cascades locally in the dendrites, or, more often, is delivered to the cell soma via retrograde axonal transport, where it modulates gene expression. BDNF activation of TrkB is critical for the initiation of axonal transport, and this cellular process relies on the interaction of numerous adaptor …

Reducing The Rate Of Misdiagnosis Of Postural Orthostatic Tachycardia Syndrome, Isabelle C. Gill

Honors Undergraduate Theses

Postural orthostatic tachycardia syndrome (POTS) is a common yet frequently misdiagnosed dysautonomia characterized by a significant increase in heart rate upon standing. POTS patients experience severe fatigue, dizziness, pre-syncope, and a diminished quality of life. The intent of this thesis is to investigate factors contributing to POTS misdiagnosis and develop a proposal for improving diagnostic procedures. The first part of this thesis presents an overview of other frequently misdiagnosed conditions, providing an understanding of the basis for the diagnostic problems in POTS and methods to combat such difficulties. The second part of this thesis details a meta-analysis performed on POTS …

Investigating The Role Of The Gut Microbiome In Huntington Disease, Casey G. Hart

Honors Undergraduate Theses

Huntington disease (HD) is an inherited neurodegenerative disease caused by a trinucleotide repeat expansion in the huntingtin (HTT) gene. Metabolic dysfunction is a feature of HD that is recapitulated in HD mouse models. Our lab has shown that circadian feeding rhythms are disrupted in humanized HD mice and restored by suppression of brain HTT. Furthermore, when circadian feeding rhythm is artificially restored, in addition to normalization of metabolic function, liver and striatal HTT is temporarily reduced, demonstrating that HTT is involved in gut-brain feedback. The gut microbiome, which can regulate gut-brain feedback, has been implicated in the pathogenesis …

Elevated L-Lactate Drives Major Cellular Pathologies Associated With Neurodegeneration, Jessica Behnke

Dissertations, Master's Theses and Master's Reports

Within the past few decades, lactate research has expanded from initial findings deeming lactate as a dead-end metabolic product to recognition of lactate’s role as a potential energy substrate in the CNS. Due to the tight relationship between lactate and energy metabolism, interest in the scientific community has been mounting around associations among metabolic dysregulation, elevated lactate and neurodegenerative states such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, ischemia/reperfusion (AD, PD, ALS, I/R injuries), and physiological aging, however underlying cellular mechanisms and/or facilitators for neuronal degeneration pathologies still remain unknown. Here, we tested several hypotheses that implicate L-lactate to various neurodegenerative …

Ccl11 As A Biomarker For The In Vivo Diagnosis Of Chronic Traumatic Encephalopathy, Robert Weissenfels

CMC Senior Theses

Chronic traumatic encephalopathy is the neurodegenerative disease that is ascribed to the long term development of cognitive, behavioral, emotional, and motor deficits as a result of the exposure to high amounts of sub concussive traumatic brain injuries. The disease has gained recent popularity in the media for its prevalence in American football as a response to recent research that has suggested the prominence of the disease in nearly every NFL player that is examined post mortem. This has produced a growing concern for the consequences of head impact and participation in contact sports. Despite media attention, little is currently known …

Screening Techniques For Alzheimer’S Disease, Christina Nicole Brooks

Physician Assistant Scholarly Project Papers

Alzheimer’s disease is a neurodegenerative disease that affects more than 55 million Americans. By the year 2050, experts project this disease will have increased three fold. Many screening techniques have been investigated to detect this disease early and begin treatment to slow its progression. The purpose of this study was to explore which medical modalities are the most effective for screening of Alzheimer’s disease. This literature review includes three databases, including PubMed, CINHAL, and Cochrane Database of Systematic Reviews. Topics that were researched include: cognitive screening tests, neuroimaging, laboratory diagnostic testing, DNA, and combined studies. Research was conducted from October …

Insulin-Like Growth Factor-1 Overexpression Mediates Hippocampal Remodeling And Plasticity Following Tbi, Erica Latrice Littlejohn

Theses and Dissertations--Physiology

Every year over 2.5 million traumatic brain injuries (TBI) occur and are the leading cause of death and disability among adolescents. There are no approved treatments for TBI. Survivors suffer from persistent cognitive impairment due to posttraumatic tissue damage and disruption of neural networks which significantly detract from their quality of life. Posttraumatic cognitive impairment depends in part on the brain's limited ability to repair or replace damaged cells. Immature neurons in the hippocampus dentate gyrus, a brain region required for learning and memory, are particularly vulnerable to TBI. Insulin-like growth factor-1 (IGF1) is a potential therapeutic for TBI because …

The Utility Of Multidisciplinary Rehabilitation As A Treatment Strategy For Circadian Rhythm And Sleep Disturbances In Premanifest Huntington’S Disease, Danielle Megan Bartlett

Theses: Doctorates and Masters

Background: Huntington’s disease (HD) is a rare, neurodegenerative disease caused by an expanded cytosine-adenine-guanine (CAG) sequence in the Huntingtin gene, resulting in the production of an aberrant protein, mutant huntingtin (mHTT). The mHTT protein exhibits a toxic loss and gain in function, leading to degeneration of neurons in the brain. Consequently, the classic triad of motor, cognitive and mood features of the disease develop. Among the earliest features of HD are circadian rhythm and sleep disturbances. These anomalies present many years prior to formal clinical diagnosis of HD and, while it has been postulated that these disturbances arise as a …