Medical Neurobiology Commons^™

Investigations Of Interleukin-1 Alpha As A Novel Stroke Therapy In Experimental Ischemic Stroke, Kathleen Elizabeth Salmeron

Theses and Dissertations--Neuroscience

Stroke is a leading cause of death and disability worldwide. Although rapid recognition and prompt treatment have dropped mortality rates, most stroke survivors are left with permanent disability. Approximately 87% of all strokes result from the thromboembolic occlusion of the cerebrovasculature (ischemic strokes). Potential stroke therapeutics have included anti-inflammatory drugs, as well as many other targets with the goal of mitigating the acute and chronic inflammatory responses typically seen in an ischemic stroke. While these approaches have had great success in preclinical studies, their clinical translation has been less successful. Master inflammatory cytokines, such as IL-1, are of particular interest. …

Intermittent Hypoxemia In Preterm Infants, Elie G. Abu Jawdeh

Theses and Dissertations--Clinical and Translational Science

Intermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO₂). Virtually all preterm infants have IH events. Extremely preterm infants have hundreds of IH events per day. The extent of IH is not apparent clinically as accurately documenting cardiorespiratory events for day-to-day patient care management is challenging. High resolution pulse oximeters with 2 second averaging time are currently the ideal methods to measure IH. We have developed novel methods and processes to accurately and efficiently calculate an IH profile that reflects to spectrum of the problem.

The natural progression of IH is dynamic. There is low …

The Potential Synergistic Behaviour Of Inter- And Intra-Genus Probiotic Combinations In The Pattern And Rate Of Short Chain Fatty Acids Formation During Fibre Fermentation, Warnakulasuriya M. A. D. B. Fernando, Steve H. Flint, K. K. D. S. Ranaweera, Arthur Bamunuarachchi, Stuart K. Johnson, Charles S. Brennan

Research outputs 2014 to 2021

This study compared the rate of short chain fatty acid (SCFA) production by different probiotic combinations of Lactobacillus and Bifidobacterium to determine any synergistic effects. Six different fibre fractions were fermented with nine combinations of Lactobacillus rhamnosus (LR), Lactobacillus acidophilus (LA), Bifidobacterium longum (BL) and Bifidobacterium breve (BB) for 0, 6, 24 and 48 h. SCFAs were quantified by gas chromatography. Inter-genus combinations of bacteria produced more SCFA, especially BB + BL + LR, compared to intra-genus that yielded the lowest SCFA production. Acetate was the most abundant, while propionate and butyrate were the most utilised. The SCFA formation was …

Neuromuscular Junction Defects In A Mouse Model Of Charcot-Marie-Tooth Disease Type 2o, Thywill Sabblah

Electronic Theses and Dissertations

Charcot Marie Tooth disease (CMT) represents the most common inheritable peripheral group of motor and sensory disorders; affecting 1 in 2500 people worldwide. Individuals with CMT experience slow progressing weakness of the muscle, atrophy, mild loss of motor coordination and in some cases loss of sensory function in the hands and feet which could ultimately affect mobility. Dynein is an essential molecular motor that functions to transport cargos in all cells. A point mutation in the dynein heavy chain was discovered to cause CMT disease in humans, specifically CMT type 2O. We generated a knock-in mouse model bearing the same …

Novel Therapeutic Approaches For Juvenile Neuronal Ceroid Lipofuscinosis (Cln3), Megan Elizabeth Bosch

Theses & Dissertations

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by autosomal recessive mutations in CLN3. Neuronal loss is thought to occur via glutamate excitotoxicity; however, little is known about neuron-astrocyte glutamate regulation in JNCL. We discovered that Cln3^Δex7/8 astrocytes have significantly lower basal spontaneous Ca²⁺ oscillations and decreased responses to glutamate, indicating a disrupted signaling network. Cln3^Δex7/8 astrocytes also displayed significantly lower basal mitochondrial respiration and ATP production, suggesting impaired metabolic functions. Concurrent with diminished astrocyte metabolism and Ca²⁺ signaling, Cln3^Δex7/8 neurons were hyper-responsive to glutamate stimulation. These studies suggest that CLN3 …

The Climate Of Neurofeedback: Scientific Rigour And The Perils Of Ideology, Robert T. Thibault, Michael Lifshitz, Amir Raz

Psychology Faculty Articles and Research

Over the last six decades, an in-group with ideological and financial stakes has been conducting sub-par research to develop an ostensibly effective clinical intervention: EEG-neurofeedback. More recently, however, a string of independent studies featuring increased scientific rigour and tighter experimental controls has challenged the foundation on which EEG-neurofeedback stands. Earlier this year, Brain published one of the most robust EEG-neurofeedback experiments to date (Schabus et al., 2017), which sparked a flurry of correspondence concerning the therapeutic value of neurofeedback (Fovet et al., 2017; Schabus, 2017); notably, a parallel discussion continues in Lancet Psychiatry …

Analysis Of Diagnostic, Preventive, And Disease-Modifying Therapeutic Measures Of Alzheimer’S Disease, Ghazal Habib Havoutis

HCNSO Student Capstones

Alzheimer’s disease (AD) is the most common late-onset neurodegenerative disorder and cause of dementia, characterized by the formation of neurofibrillary tangles and senile plaque deposits. The heterogeneous nature of the disease (both genetically and environmentally) makes it difficult to prevent or cure. Without prevention, the prevalence of AD is expected to triple by 2050. However, because the diagnosis of AD is usually preceded by years of cognitive impairment, early detection may aid in reducing prevalence. Thus, there is a need for validated diagnostic measures for early and improved diagnosis and prevention. In this review, current and ongoing classifiers of early …

Pitx3null Mutant (Striatal Dopamine-Deficient) Mice Have Exaggerated Spiny Projection Neuron Responses To L-Dopa And D1 Agonism And Lack Baseline Striatonigral Spiking, Ben Sagot

Theses and Dissertations (ETD)

L-3,4 dihidroxyphenylalanine (l-DOPA) strongly stimulates motor activity in parkinsonian patients and animal models of Parkinson's disease. Severe striatal dopamine (DA) loss characterizes Parkinson's disease and its animal models. Given the canonical rate model of Parkinson's Disease pathophysiology based on differences in DA pharmacology manifesting as electrophysiological differences in striatal projection neuron (SPN) spike rates, SPNs should increase spiking during the motor response to l-DOPA. In fact, stimulating specific subsets of these neurons to spike in freely-moving wild type and parkinsonian animals causes or inhibits motor activity as predicted. However, pharmacological effects of DA deficiency, let alone those of DA replacement, …

Assessing Neuronal Synchrony And Brain Function Through Local Field Potential And Spike Analysis, Samuel Stuart Mcafee

Theses and Dissertations (ETD)

Studies of neuronal network oscillations and rhythmic neuronal synchronization have led to a number of important insights in recent years, giving us a better understanding of the temporal organization of neuronal activity related to essential brain functions like sensory processing and cognition. Important principles and theories have emerged from these findings, including the communication through coherence hypothesis, which proposes that synchronous oscillations render neuronal communication effective, selective, and precise. The implications of such a theory may be universal for brain function, as the determinants of neuronal communication inextricably shape the neuronal representation of information in the brain. However, the study …

Modeling Post Stroke Respiratory Dysfunction, Apneas And Cognitive Decline, Anthony Patrizz

Dissertations and Theses (Open Access)

Modeling Post Stroke Respiratory Dysfunction,

Apneas and Cognitive Decline

Anthony Patrizz, B.A.

Advisory Professor: Louise McCullough M.D., Ph.D.

Stroke is a major cause of mortality and the leading cause of long-term disability in the US. More than 60% of individuals suffering a first time stroke develop respiratory dysfunction, prolonging recovery and increasing mortality. Post-stroke cognitive decline is a major contributor to disability and nursing home placement, therefore the cognitive consequences of Stroke Induced Respiratory Dysfunction (SIRD) need to be explored if we hope to enhance functional recovery. The first step towards treatment of the negative consequences of SIRD is the …

Exercise, Learning And Emotional Health: Interdisciplinary Approaches To Translational Action, Tessa L. Koschel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Exercise positively effects physical, psychological and neurological wellbeing. Though the population at large is becoming increasingly aware of the multi-faceted benefits of exercise, the majority of people fail to meet daily exercise recommendations. Largely, demands of everyday life such as work, school and family take priority over fitness. The issue therefore becomes a matter of time. In a world of media multi-tasking and immediate gratification, the challenge to health professionals becomes incorporation and manipulation of these consistencies to improve exercise uptake and adherence. Focus must shift from the idea of making additional time for exercise, to adding exercise to time …

Generation Of A Patient-Derived Brain Metastasis Breast Cancer Cell Line Via Novel Orthotopic Injection Placement And Serial Mouse Transplantation To Develop Pdx Mouse Model, Amber L. Lacrosse, Denise M. Coley, Paul J. Mintz, Santhi D. Konduri, Richard A. Rovin, Amin B. Kassam

Journal of Patient-Centered Research and Reviews

Background: The incidence of brain metastasis appears to be increasing, potentially due to advanced technology that aids early diagnosis. Patient-derived xenografts (PDX) have high translational value, as these models retain key functional characteristics of the patient tumor. PDX models are useful to understand the molecular basis of tumorigenesis and to identify new treatment targets. However, generating a first-line PDX model is challenging as engraftment failure is high. Serial transplanting tumor tissue via mouse-to-mouse propagation increases engraftment rates and decreases PDX development time. Herein we report methods to generate a PDX cell line from patient-derived tumor tissue that includes the cerebral …

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) …

Trkb-Enhancer Facilitates Functional Recovery After Traumatic Brain Injury, John Marshall, Joanna Szmydynger-Chodobska, Mengia S. Rioult-Pedotti, Kara Lau, Andrea T. Chin, Siva K. Reddy Kotla, Rakesh Tiwari, Keykavous Parang, Steven W. Threlkeld, Adam Chodobski

Pharmacy Faculty Articles and Research

Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI. Moderate to severe TBI elicits neuroinflammation and c-Jun-N-terminal kinase (JNK) activation, which is associated with memory deficits. Here we demonstrate that CN2097 significantly reduces the post-traumatic synthesis of proinflammatory mediators and inhibits the …

Thiamine Deficiency And Neurodegeneration: The Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, And Autophagy, Dexiang Liu, Zunji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Thiamine (vitamin B1) is an essential nutrient and indispensable for normal growth and development of the organism due to its multilateral participation in key biochemical and physiological processes. Humans must obtain thiamine from their diet since it is synthesized only in bacteria, fungi, and plants. Thiamine deficiency (TD) can result from inadequate intake, increased requirement, excessive deletion, and chronic alcohol consumption. TD affects multiple organ systems, including the cardiovascular, muscular, gastrointestinal, and central and peripheral nervous systems. In the brain, TD causes a cascade of events including mild impairment of oxidative metabolism, neuroinflammation, and neurodegeneration, which are commonly observed in …

A Protocol For The Administration Of Real-Time Fmri Neurofeedback Training, Matthew Sherwood, Emily E. Diller, Elizabeth Ey, Subhashini Ganapathy, Jeremy T. Nelson, Jason G. Parker

Neuroscience, Cell Biology & Physiology Faculty Publications

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can …

Milder Alzheimer's Disease Pathology In Heart Failure And Atrial Fibrillation, Luciano A. Sposato, Estefania Ruiz Vargas, Patricia M. Riccio, Jon B. Toledo, John Q. Trojanowski, Walter A. Kukull, Lauren E. Cipriano, Antonia Nucera, Shawn N. Whitehead, Vladimir Hachinski

Anatomy and Cell Biology Publications

Introduction:Heart failure (HF) and atrial fibrillation (AF) have been associated with a higher risk of Alzheimer’s disease (AD). Whether HF and AF are related to AD by enhancing AD neuropathological changes is unknown.

Methods:We applied network analyses and multiple logistic regression models to assess the association between HF and AF with severity of AD neuropathology in patients from the National Alzheimer’s Coordinating Center database with primary neuropathological diagnosis of AD.

Results:We included 1593 patients, of whom 129 had HF and 250 had AF. HF and AF patients were older and had milder AD pathology. In the network …

The Neural Encoding Of Reward In The Striatal-Pallidal Circuitry, Chung Lung Chan

Dissertations (1934 -)

Humans and animals are constantly exposed to external stimuli. The ability to process reward value of a stimulus is critical to guiding appropriate behavior and essential for survival. These processes are regulated by neuronal activity and neurochemical signaling in the reward circuitry, particularly in the nucleus accumbens (NAc). The NAc receives dopaminergic inputs from the midbrain ventral tegmental area (VTA) and sends GABAergic projections to the ventral pallidum (VP). Electrophysiological studies have characterized phasic neuronal responses in the NAc that differential encode appetitive and aversive taste stimuli. Exposure to an appetitive taste stimulus evoked predominantly phasic inhibitory responses in the …

Efficient Synthesis Of Cn2097 Using In Situ Activation Of Sulfhydryl Group, Shaban Darwish, Keykavous Parang, John Marshall, Dennis J. Goebel, Rakesh Tiwari

Pharmacy Faculty Articles and Research

CN2097 (R₇Cs-sCYK[KTE(β-Ala)]V) is a rationally designed peptidomimetic that shows effectiveness in preclinical models for the treatment of neurological disorders, such as Angelman syndrome, traumatic brain injury (TBI), and stroke. Because of its potential therapeutic activity for the treatment of human CNS disorders, there was an urgent need to develop an efficient strategy for large-scale synthesis of CN2097. The synthesis of CN2097 was accomplished using Fmoc/tBu solid phase chemistry in multiple steps. Two different peptide fragments (activated polyarginine peptide Npys-sCR₇ and CYK[KTE(β-Ala)]V) were synthesized, followed by solution phase coupling in water. Activation of the polyarginine (CR₇) …

Mixed-Mode Oscillations In Pyramidal Neurons Under Antiepileptic Drug Conditions, Babak V-Ghaffari, M. Kouhnavard, Sherif M. Elbasiouny

Neuroscience, Cell Biology, & Physiology Faculty Publications

Subthreshold oscillations in combination with large-amplitude oscillations generate mixedmode oscillations (MMOs), which mediate various spatial and temporal cognition and memory processes and behavioral motor tasks. Although many studies have shown that canard theory is a reliable method to investigate the properties underlying the MMOs phenomena, the relationship between the results obtained by applying canard theory and conductancebased models of neurons and their electrophysiological mechanisms are still not well understood. The goal of this study was to apply canard theory to the conductance-based model of pyramidal neurons in layer V of the Entorhinal Cortex to investigate the properties of MMOs under …

Effects Of Phosphodiesterase 3a Modulation On Murine Cerebral Microhemorrhages, Rachita K. Sumbria, Vitaly Vasilevko, Mher Mahoney Grigoryan, Annlia Paganini-Hill, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects. As an initial step in the development of a therapy that simultaneously treats CMB and ischemic stroke, we hypothesized that inhibition of the PDE3A pathway is protective against CMH development.

Methods: The effect of PDE3A pathway inhibition was studied in the inflammation-induced and …

Source Localization Of Brain States Associated With Canonical Neuroimaging Postures, Michael Lifshitz, Robert T. Thibault, Raquel R. Roth, Amir Raz

Psychology Faculty Articles and Research

Cognitive neuroscientists rarely consider the influence that body position exerts on brain activity; yet, postural variation holds important implications for the acquisition and interpretation of neuroimaging data. Whereas participants in most behavioral and EEG experiments sit upright, many prominent brain imaging techniques (e.g., fMRI) require participants to lie supine. Here we demonstrate that physical comportment profoundly alters baseline brain activity as measured by magnetoencephalography (MEG)—an imaging modality that permits multipostural acquisition. We collected resting-state MEG data from 12 healthy participants in three postures (lying supine, reclining at 45°, and sitting upright). Source-modeling analysis revealed a broadly distributed influence of posture …

Tumor Necrosis Factor Α Inhibition For Alzheimer's Disease, Rudy Chang, Kei-Lwun Yee, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

Rat Hind Limb Nociceptive Withdrawal Response To Heat And Mechanical Stimuli Depends On Initial Position Of The Paw But Not Stimulus Location, Giavanna Verdi

Senior Honors Projects, 2010-2019

Mammals rapidly withdraw their hind limb in response to noxious stimulation, which is a protective movement known as the nociceptive withdrawal response (NWR). The NWR has been previously studied in spinalized, decerebrated and anesthetized non-human and human mammals; however, there is minimal information on the NWR in intact, unanesthetized non-human mammals.

The first specific aim was to identify the factors that determine the direction and magnitude of the NWR in intact, unanesthetized rats. Based on previous studies, we hypothesized that the location of stimulation and the initial position of the paw preceding the NWR will influence the direction and magnitude …