Nervous System Diseases Commons^™

Ion Channel Candidates Mediating Orexin Neuropeptide Actions On Brainstem Serotonergic Neurons, Saqlain Javed

NYMC Student Theses and Dissertations

A loss of neurons that synthesize the neuropeptide orexin produces the sleep disorder narcolepsy with cataplexy in humans and other animals. How symptoms of this disorder arise is not well understood, but selectively restoring orexin actions at 5-HT DR neurons rescues key symptoms (cataplexy), suggesting normal orexin signaling is important at these neurons. To better understand how orexin acts on these neurons, our lab identified a set of novel orexin actions that appear mediated by unidentified cation- permeable ion channels. To narrow down the list of possible channels, we used a bioinformatics approach to compare published gene expression profiles of …

Open Neuroscience Initiative, Austin Lim

College of Science and Health Full Text Publications

The Open Neuroscience Initiative is a free-to-use textbook

This project began as a means to overcoming the financial burden that face undergraduate neuroscience students when buying textbooks. By compiling and writing a completely free-to-access textbook that covers the foundations of a typical college introduction to neuroscience course, students would have one less obstacle to overcome in their educational career, allowing them to focus their valuable time and attention on learning rather than finances. To make this project a reality, I began with a humble tweet in May 2019 that managed to gain a tiny bit of traction among the neuroscience …

Deep Neural Network Analysis Of Pathology Images With Integrated Molecular Data For Enhanced Glioma Classification And Grading, Linmin Pei, Karra A. Jones, Zeina A. Shboul, James Y. Chen, Khan M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Gliomas are primary brain tumors that originate from glial cells. Classification and grading of these tumors is critical to prognosis and treatment planning. The current criteria for glioma classification in central nervous system (CNS) was introduced by World Health Organization (WHO) in 2016. This criteria for glioma classification requires the integration of histology with genomics. In 2017, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) was established to provide up-to-date recommendations for CNS tumor classification, which in turn the WHO is expected to adopt in its upcoming edition. In this work, we propose a novel …

The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Alzheimer’s disease is a degenerative neurological illness characterized by the deterioration of brain regions implicated in memory and cognitive function. While researchers have yet to find a cure or effective treatment, they have gained a better understanding of its pathology and development. Through years of neuroscience research, scientists have discovered much of what happens in the brain during Alzheimer’s disease onset and how this causes its symptoms; many hypotheses regarding this aspect of the illness involve temporal lobe atrophy, neurofibrillary tangles, and amyloid plaques. Although Alzheimer’s disease affects millions of people every day, it seems that most are unaware of …

Recovery From Visual Dysfunction Following Mild Traumatic Brain Injury Is Associated With Adaptive Reorganization Of Retinal Inputs To Lateral Geniculate Nucleus In The Mouse Model Utilizing Central Fluid Percussion Injury., Vishal C. Patel

Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality nationwide. Prevalence of mild TBI (mTBI) vastly outnumbers more severe forms however the associated morbidity has only recently gained public attention. Visual dysfunction is a significant component of mTBI associated morbidity with recovery of function linked with improvement in global outcomes. Examination of sensory and motor pathways in other brain injury paradigms support that recovery is largely dependent on adaptive plasticity of remaining connections. Current examinations of visual function recovery following mTBI is limited to identifying evidence for recovery and objective evidence for adaptive plasticity is limited. Therefore, …

Investigating The Role Of Integrin Beta 3 In Dendritic Arborization In The Supragranular Developing Cerebral Cortex, Zachary Logan Holley

Senior Honors Projects, 2010-2019

Integrin subunits have been implicated in axonal and dendritic outgrowth. In particular, a strong positive association has been found between mutations in integrin beta 3 (Itgb3) and autism spectrum disorder, but little is known about neuronal Itgb3 function in vivo. Many forms of autism spectrum disorder are thought to arise from dysfunctional dendritic arborization and synaptic pruning. Global knockout of Itgb3 in mice leads to autistic-like behaviors. Itgb3^-/- mice also have reduced callosal volume, a key neuroanatomical correlate of autism. Here, we test the hypothesis that Itgb3 is required for normal dendritic arborization in layer II/III pyramidal …

Seeing Eye To Eye: A Machine Learning Approach To Automated Saccade Analysis, Maigh Attre

Honors Scholar Theses

Abnormal ocular motility is a common manifestation of many underlying pathologies particularly those that are neurological. Dynamics of saccades, when the eye rapidly changes its point of fixation, have been characterized for many neurological disorders including concussions, traumatic brain injuries (TBI), and Parkinson’s disease. However, widespread saccade analysis for diagnostic and research purposes requires the recognition of certain eye movement parameters. Key information such as velocity and duration must be determined from data based on a wide set of patients’ characteristics that may range in eye shapes and iris, hair and skin pigmentation [36]. Previous work on saccade analysis has …

Quantifying Expression Of Interneuron Subtype Markers For Dlx-2 Transfected Ng2 Cells, Timothy Nolan

Honors Scholar Theses

Neurons are a post-mitotic cell population, and therefore, they are not able to regenerate in vivo after a traumatic injury. Because inhibitory GABAergic interneurons and oligodendrocyte precursor cells (OPCs) are derived from the same precursor, recent studies have focused on transforming these OPCs into GABAergic neurons. However, there are different types of GABAergic interneurons that have different electrophysiological responses, which can lead to functional differences. The Nishiyama laboratory had already used a key gene in GABAergic interneuron and OPC differentiation, Distal-less homeobox 2 (Dlx-2), to transfect OPCs; early electrophysiology tests showed most of these transfected cells behaved like immature neurons, …

Toxic Environmental Risk Factors For Alzheimer's Disease: A Systematic Review, Oluwaseyi Olayinka, Olaniyi O. Olayinka, Brook T. Alemu, Muge Akpinar-Elci, George T. Grossberg

Community & Environmental Health Faculty Publications

There is growing evidence of a possible association between toxic environmental factors and Alzheimer’s disease (AD), a disabling neurodegenerative condition with no known cause. Previous reviews of toxic environmental factors for AD either focused on occupational exposures or used a non-systematic methodology. The objective of this systematic review is to assess the evidence on the link between AD and exposure to a variety of toxic environmental risk factors beyond the work environment. Structured database search was used to identify relevant studies. Twenty-nine eligible studies examining the effect of various toxic environmental agents including electromagnetic fields, solvents, pesticides, toxic metals, and …

Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19

Student Publications & Research

Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.

Emerging Cellular And Molecular Strategies For Enhancing Central Nervous System (Cns) Remyelination., Mohammad Abu-Rub, Robert H Miller

Anatomy and Regenerative Biology Faculty Publications

Myelination is critical for the normal functioning of the central nervous system (CNS) in vertebrates. Conditions in which the development of myelin is perturbed result in severely compromised individuals often with shorter lifespans, while loss of myelin in the adult results in a variety of functional deficits. Although some form of spontaneous remyelination often takes place, the repair process as a whole often fails. Several lines of evidence suggest it is feasible to develop strategies that enhance the capacity of the CNS to undergo remyelination and potentially reverse functional deficits. Such strategies include cellular therapies using either neural or mesenchymal …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi

Neurology Faculty Publications

Background: We report a patient who developed lower facial muscle spasm at rest and bilateral facial synkinesis several months after treatment of Guillain–Barré syndrome (GBS); this finding, to our knowledge, is hitherto unreported.

Phenomenology Shown: Bilateral synkinesis, facial muscles spasm at rest, bilateral postparalytic facial syndrome.

Educational Value: Aberrant regeneration of nerve fibers post GBS, resulting in facial muscles spasm at rest, bilateral synkinesis.

A Gut Feeling: A Hypothesis Of The Role Of The Microbiome In Attention-Deficit/Hyperactivity Disorders., Xue Ming, Neil Chen, Carly Ray, Gretchen Brewer, Jeffrey Kornitzer, Robert A Steer

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Attention-deficit/hyperactivity disorder (ADHD) is a neurologic disorder characterized by hyperactivity/impulsivity and/or inattentiveness, with genetic and environmental factors contributing to the disorder. With the growing recognition of the microbiome's role in many neurological disorders, the authors propose that it may also be implicated in ADHD. Here, we describe several evolving areas of research to support this hypothesis. First, a unique composition of gut bacteria has been identified and linked to behaviors in ADHD. Second, our research found an increased incidence of 2 gastrointestinal symptoms (constipation and flatulence) in children with ADHD, as compared to controls. Finally, emerging data may be interpreted …

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 …

Simultaneous Uplc–Ms/Ms Analysis Of Two Stable Isotope Labeled Versions Of Sucrose In Mouse Plasma And Brain Samples As Markers Of Blood-Brain Barrier Permeability And Brain Vascular Space, Ekram Ahmed Chowdhury, Saad Alqahtani, Raktima Bhattacharya, Reza Mehvar, Ulrich Bickel

Pharmacy Faculty Articles and Research

Blood Brain Barrier (BBB) permeability is frequently compromised in the course of diseases affecting the central nervous system (CNS). Sucrose is a low molecular weight, hydrophilic marker with low permeability at the naive BBB and therefore one of the widely used indicators of barrier integrity. Our laboratory recently developed a highly sensitive UPLC-MS/MS method for stable isotope labelled [13C12]sucrose in biological matrices. Correction of total brain concentration for contribution of intravascular space is required in such experiments in order to accurately measure BBB permeability, and it is often accomplished by vascular perfusion with buffer solutions prior to brain sampling. The …

Brain Imaging In Older Patients With Delirium, Laila M. Hasan, Ariba Khan, Maharaj Singh, Michael L. Malone

Journal of Patient-Centered Research and Reviews

Background: Delirium is a common, serious and costly condition in older patients admitted to the hospital. This study describes the prevalence and results of brain imaging among a cohort of older hospitalized patients with and without delirium.

Purpose: Investigate the frequency and results of brain imaging in older patients with delirium as compared to those without delirium.

Methods: This was a cross-sectional study. Data were collected on hospitalized patients age 65 years or older who were admitted to 3 hospitals in Milwaukee, Wisconsin, during a 1-month period in the fall of 2013. Subjects were tested for delirium via the “Confusion …

Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas

Pharmacy Faculty Articles and Research

Background: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer’s disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors.

Methods: The presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) …

Neuroinflammation In Alzheimer's Disease And Vascular Cognitive Impairment, Erica M. Weekman

Theses and Dissertations--Physiology

It was once believed that the brain was immunologically privileged with no resident or infiltrating immune cells; however, now it is understood that the cells of the brain are capable of a wide range of inflammatory processes and phenotypes. Inflammation in the brain has been implicated in several disease processes such as Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID); however, the role of inflammation in these two dementias is poorly understood.

When we stimulated a pro-inflammatory phenotype with an adeno-associated viral vector in a transgenic mouse model of AD that develops Aβ plaques, we saw a pro-inflammatory …

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …

Can Gait Signatures Provide Quantitative Measures For Aiding Clinical Decision-Making? A Systematic Meta-Analysis Of Gait Variability Behavior In Patients With Parkinson’S Disease, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

A disturbed, inconsistent walking pattern is a common feature of patients with Parkinson's disease (PwPD). Such extreme variability in both temporal and spatial parameters of gait has been associated with unstable walking and an elevated prevalence of falls. However, despite their ability to discretise healthy from pathological function, normative variability values for key gait parameters are still missing. Furthermore, an understanding of each parameter's response to pathology, as well as the inter-parameter relationships, has received little attention. The aim of this systematic literature review and meta-analysis was therefore to define threshold levels for pathological gait variability as well as to …

Reverse Engineering A Kinetic Model Of A Dopaminergic Neuron To Apoptosis, Johnathan Morris

Biology and Medicine Through Mathematics Conference

No abstract provided.

Revealing The Quality Of Movement: A Meta-Analysis Review To Quantify The Thresholds To Pathological Variability During Standing And Walking, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Neuromotor processes are inherently noisy, which results in variability during movement and fluctu-ations in motor control. Although controversial, low levels of variability are traditionally considered healthy, while increased levels are thought to be pathological. This systematic review and meta-analysisof the literature investigates the thresholds between healthy and pathological task variability.

After examining 13,195 publications, 109 studies were included. Results from over 3000 healthy sub-jects and 2775 patients revealed an overall positive effect size of pathology on variability of 0.59 forwalking and 0.80 for sway. For the coefficient of variation of stride time (ST) and sway area (SA), upperthresholds of 2.6% …

Looking To The Future Of Stroke Treatment: Combining Recanalization And Neuroprotection In Acute Ischemic Stroke, Michael E. Maniskas

Theses and Dissertations--Neuroscience

Stroke is the 5^th leading cause of death in the U.S. with 130,000 deaths and around 800,000 affected annually. Currently, there is a significant disconnect between basic stroke research and clinical stroke therapeutic needs. Few animal models of stroke target the large vessels that produce cortical deficits seen in the clinical setting. Also, current routes of drug administration, intraperitoneal and intravenous, do not mimic the clinical route of intra-arterial drug administration. To bridge this divide, we have retro-engineered a mouse model of stroke from the current standard of care for emergent large vessel occlusion (ELVO) stroke, endovascular thrombectomy, to …

The Physiology And Psychology Of Exercise And Parkinson's Disease, Jess Gibson

Senior Honors Theses

Parkinson’s disease is one of the most common degenerative neurological disorders and is currently lacking a cure. While physicians have long debated over the best treatment for Parkinson’s symptoms, treatments such as oral medication and deep brain stimulation have not yet shown to be a permanent solution to the disease. Recently, exercise has emerged as a contender in the fight against Parkinson’s and physicians and physiotherapists have been investigating the benefits of prescribing exercise programs to patients in an effort to slow progression of Parkinson’s symptoms. The following presents an analysis of the effects of exercise on Parkinson’s symptoms and …

Amyotrophic Lateral Sclerosis, The Primary Motor Neuron Disease, Jacob P. Naumann

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

Amyotrophic lateral sclerosis is a degenerative neurological disease that damages nerve cells in the brain, in particular the neurons that are involved in voluntary muscle movements. Internationally the disorder is also known as Charcot’s disease and motor neuron disease. In the United States, amyotrophic lateral sclerosis is often referred to as Lou Gehrig’s disease, motor neuron disease, and more colloquially ALS. Amyotrophic Lateral Sclerosis is the most prominent of the five motor neuron diseases, distinguishing itself from the others through degeneration of both upper motor neurons (UMN) and lower motor neurons (LMN) respectively. The “Father of neurology” Jean-Marie Charcot founded …

Novel Advances In Alzheimer's Disease, Jacob P. Naumann

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

Alzheimer’s disease, the most common form of dementia in adults, is a progressive degenerative neurological disease that affects memory, cognition, and behavior. Dr. Alois Alzheimer discovered and diagnosed the irreversible disease in 1906 after documenting the famous case of Auguste Deter.¹ Since the discovery of the disease, numerous advances have made it possible to not only better understand the causal factors, but also to improve the medical diagnosis and preventative measures that healthcare providers can implement. For the first time since 1984, the National Institute on Aging (NIAA) and the Alzheimer’s Association (AA) proposed and published new diagnostic guideline …

Pathological Effects Of Repeated Concussive Tbi In Mouse Models: Periventricular Damage And Ventriculomegaly, Richard H. Wolferz Jr.

Honors Scholar Theses

Repeated concussive traumatic brain injury (rcTBI) is the most prominent form of head injury affecting the brain, with an estimated 1.7 million Americans affected each year (Kuhn 2012). Neurologists have been concerned about the danger of repeated head impacts since the 1920’s, but researchers have only begun to understand the long-term effects of rcTBI (McKee 2009). Although symptoms can be as mild as dizziness, current research suggests that multiple concussions can lead to a progressive degenerative brain disease known as chronic traumatic encephalopathy (CTE) (Luo 2008, McKee 2009, Kane 2013). Research on the brain is just beginning to scratch the …

Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko

Anatomy and Regenerative Biology Faculty Publications

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental …

Brain Blast 2015 Speakers Poster, Annie Leslie

Brain Blast

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