Medical Physiology Commons^™

The Role Of Panx3 In Age-Associated And Injury-Induced Intervertebral Disc Degeneration, Meaghan Serjeant, Paxton M. Moon, Diana Quinonez, Silvia Penuela, Frank Beier, Cheryle A. Séguin

Physiology and Pharmacology Publications

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for Panx3 expression in the intervertebral disc (IVD), its function in this cartilaginous joint structure remained unknown. Using Panx3 knockout mice, this study investigated the role of Panx3 in age-associated IVD degeneration and degeneration induced by annulus fibrosus (AF) needle puncture. Loss of Panx3 did not significantly impact the progression of age-associated histopathological IVD degeneration; however, loss of Panx3 was associated with decreased gene expression of Acan, Col1a1, Mmp13 and Runx2 and altered localization …

Macrophage-Engineered Vesicles For Therapeutic Delivery And Bidirectional Reprogramming Of Immune Cell Polarization, Khaga R. Neupane, J. Robert Mccorkle, Timothy J. Kopper, Jourdan E. Lakes, Surya P. Aryal, Masud Abdullah, Aaron A. Snell, John C. Gensel, Jill M. Kolesar, Christopher I. Richards

Spinal Cord and Brain Injury Research Center Faculty Publications

Macrophages, one of the most important phagocytic cells of the immune system, are highly plastic and are known to exhibit diverse roles under different pathological conditions. The ability to repolarize macrophages from pro-inflammatory (M1) to anti-inflammatory (M2) or vice versa offers a promising therapeutic approach for treating various diseases such as traumatic injury and cancer. Herein, it is demonstrated that macrophage-engineered vesicles (MEVs) generated by disruption of macrophage cellular membranes can be used as nanocarriers capable of reprogramming macrophages and microglia toward either pro- or anti-inflammatory phenotypes. MEVs can be produced at high yields and easily loaded with diagnostic molecules …

The Association Of Circulating Amylin With Β-Amyloid In Familial Alzheimer's Disease, Han Gia Ly, Nirmal Verma, Savita Sharma, Deepak Kotiya, Sanda Despa, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Donna M. Wilcock, Larry B. Goldstein, Rita Guerreiro, José Brás, Angela J. Hanson, Suzanne Craft, Andrew J. Murray, Geert Jan Biessels, Claire Troakes, Henrik Zetterberg, John Hardy, Tammaryn Lashley, Alzheimer’S Disease Exome Sequencing Group, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Introduction

This study assessed the hypothesis that circulating human amylin (amyloid‐forming) cross‐seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).

Methods

Evidence of amylin‐AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non‐APP/PS1 rats.

Results

Amylin‐Aβ cross‐seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected …

Neurogenic Hypertension Mediated Mitochondrial Abnormality Leads To Cardiomyopathy: Contribution Of Upr Mt And Norepinephrine-Mir- 18a-5p-Hif-1Α Axis, Shyam Sundar Nandi, Kenichi Katsurada, Sushil K. Mahata, Kaushik K. Patel

Journal Articles: Cellular & Integrative Physiology

Aims: Hypertension increases the risk of heart disease. Hallmark features of hypertensive heart disease is sympathoexcitation and cardiac mitochondrial abnormality. However, the molecular mechanisms for specifically neurally mediated mitochondrial abnormality and subsequent cardiac dysfunction are unclear. We hypothesized that enhanced sympatho-excitation to the heart elicits cardiac miR-18a-5p/HIF-1α and mitochondrial unfolded protein response (UPR^mt) signaling that lead to mitochondrial abnormalities and consequent pathological cardiac remodeling. Methods and Results: Using a model of neurogenic hypertension (NG-HTN), induced by intracerebroventricular (ICV) infusion of Ang II (NG-HTN; 20 ng/min, 14 days, 0.5 μl/h, or Saline; Control, 0.9%) through osmotic mini-pumps in Sprague-Dawley …

Viability Of Physiologically Timed Relaxation Interventions In Children With Asd, Nicholas Mendez

CMC Senior Theses

Autism Spectrum Disorder (ASD) is an increasingly common developmental disorder that changes how people experience the world and affects individuals’ social interactions and often leads to many adverse behaviors. Current literature dictates that a primary contributor to these adverse behaviors is that those with ASD have difficulty determining their own emotional states and determining the physiological signals that their body sends them. A study by Dr. Sarabadani et al. determined that it was possible to monitor the physiology of an individual with ASD and correlate certain signals to emotions, such as stress. These findings indicate the feasibility of establishing a …

Novel Mammalian Models For Understanding And Treating Spinal Cord Injury, Michael B. Orr

Theses and Dissertations--Physiology

Spinal cord injury (SCI) is devastating and often leaves the injured individual with persistent dysfunction. The injury persists because humans have poor wound repair and there are no pharmacologic treatments to induce wound repair after SCI. The continued efforts to discover therapeutic targets and develop treatments heavily relies on animal models. The purpose of this project is to develop and study novel mammalian models of SCI to provide insights for the development and effective implementation of SCI therapies.

Lab mice (Mus musculus) are a powerful tool for recapitulating the progression and persistent damage evident in human SCI, but …

Novel Mechanisms Of Neuronal And Hormonal Regulation Of Large Intestinal Electrolyte Transport, Andrew John Nickerson

Graduate Theses, Dissertations, and Problem Reports (ETD)

The mammalian colon plays a vital role in maintaining overall electrolyte and fluid homeostasis in the body, and it possesses the ability to either secrete or absorb water depending upon the needs of the organism. Secretion or absorption of electrolyte ions, such as Na⁺, Cl^- and K⁺, drives the movement of water across the colonic epithelium – the inner gut lining where all transport takes place. Aberrant absorptive and/or secretory activity within the colonic epithelium is central to the pathogenesis of many gastrointestinal diseases, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), constipation …

Physiological Measurements For Real-Time Fatigue Monitoring In Train Drivers: Review Of The State Of The Art And Reframing The Problem, Bojana Bjegojevic, Maria Chiara Leva, Nora Balfe, Sam D. Cromie, Luca Longo

Conference papers

The impact of fatigue on train drivers is one of the most important safety-critical issues in rail. It affects drivers’ performance, significantly contributing to railway incidents and accidents. To address the issue of real-time fatigue detection in drivers, most reliable and applicable psychophysiological indicators of fatigue need to be identified. Hence, this paper aims to examine and present the current state of the art in physiological measures for real-time fatigue monitoring that could be applied in the train driving context. Three groups of such measures are identified: EEG, eye-tracking and heart-rate measures. This is the first paper to provide the …

Deep Brain Stimulation Of The Subcallosal Cingulate Gyrus In The Treatment Of Treatment Resistant Depression, Megan Caravas, Melanie Sov

Physician Assistant Capstones, 2020-current

Objective: a systematic review to determine the efficacy of deep brain stimulation (DBS) targeting the subcallosal cingulate gyrus (SCG) for the treatment of treatment resistant depression (TRD). Methods: PubMed database was utilized in a search for clinical randomized control trials that were completed after the year 2000, using the terms deep brain stimulation, treatment resistant depression, and subcallosal cingulate gyrus. Results: Three clinical trials were chosen based on specific inclusion criteria as noted in the PRISMA flow chart (Chart 1). The results of the three articles showed various discrepancies. Two of the three studies demonstrated some statistical significance in reduction …

Electrophysiological And Imaging Calcium Biomarkers Of Aging In Male And Female 5×Fad Mice, Adam O. Ghoweri, Lara Ouillette, Hilaree N. Frazier, Katie L. Anderson, Ruei-Lung Lin, John C. Gant, Rachel Parent, Shannon Moore, Geoffrey G. Murphy, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: In animal models and tissue preparations, calcium dyshomeostasis is a biomarker of aging and Alzheimer's disease that is associated with synaptic dysfunction, neuritic pruning, and dysregulated cellular processes. It is unclear, however, whether the onset of calcium dysregulation precedes, is concurrent with, or is the product of pathological cellular events (e.g., oxidation, amyloid-β production, and neuroinflammation). Further, neuronal calcium dysregulation is not always present in animal models of amyloidogenesis, questioning its reliability as a disease biomarker.

OBJECTIVE: Here, we directly tested for the presence of calcium dysregulation in dorsal hippocampal neurons in male and female 5×FAD mice on …

Oral Gavage Delivery Of Stable Isotope Tracer For In Vivo Metabolomics, Holden C. Williams, Margaret A. Piron, Grant K. Nation, Adeline E. Walsh, Lyndsay E. A. Young, Ramon C. Sun, Lance A. Johnson

Sanders-Brown Center on Aging Faculty Publications

Stable isotope-resolved metabolomics (SIRM) is a powerful tool for understanding disease. Advances in SIRM techniques have improved isotopic delivery and expanded the workflow from exclusively in vitro applications to in vivo methodologies to study systemic metabolism. Here, we report a simple, minimally-invasive and cost-effective method of tracer delivery to study SIRM in vivo in laboratory mice. Following a brief fasting period, we orally administered a solution of [U-¹³C] glucose through a blunt gavage needle without anesthesia, at a physiological dose commonly used for glucose tolerance tests (2 g/kg bodyweight). We defined isotopic enrichment in plasma and tissue at …

The Acute Effects Of 5 Fluorouracil On Skeletal Muscle Resident And Infiltrating Immune Cells In Mice, Brandon N. Vanderveen, Alexander T. Sougiannis, Kandy T. Velazquez, James A. Carson, Daping Fan, E. Angela Murphy

Faculty Publications

5 fluorouracil (5FU) has been a first-choice chemotherapy drug for several cancer types (e.g., colon, breast, head, and neck); however, its efficacy is diminished by patient acquired resistance and pervasive side effects. Leukopenia is a hallmark of 5FU; however, the impact of 5FU-induced leukopenia on healthy tissue is only becoming unearthed. Recently, skeletal muscle has been shown to be impacted by 5FU in clinical and preclinical settings and weakness and fatigue remain among the most consistent complaints in cancer patients undergoing chemotherapy. Monocytes, or more specifically macrophages, are the predominate immune cell in skeletal muscle which regulate turnover and homeostasis …

Focal Cortical Dysplasia With Prolonged Ictal Asystole, A Case Report, Ahmad Wali, Fowzia Siddiqui

Section of Neurology

Introduction: Cortical dysplasia carries significant morbidities such as seizures and delayed milestones. Focal cortical dysplasia (FCD) causes refractory epilepsy with various seizure types depending on the location and extent of the dysplasia. FCD in the temporal region and the insular cortex may cause ictal bradycardia (IB) and ictal asystole (IA). Video EEG (VEEG) with simultaneous EKG recording can better diagnose these cardiac abnormalities in FCD. We describe a case of refractory epilepsy. The patient's clinical seizures were usually followed by syncope. VEEG revealed frequent seizures some of which were associated with prolonged ictal asystole.
Results: A 15 years old female …

Apneic Oxygenation: An Adjunctive Therapy For Laryngoscopy During Anesthesia Induction, Yaro Hoffman

Doctoral Projects

Endotracheal intubation is an essential component within the skill set of anesthesia providers. Rapid arterial desaturation remains a primary risk factor during laryngoscopy and intubation. The risk for hypoxemia exists because during endotracheal intubation, patients are apneic or hypo-ventilating (Wong et al., 2017). Apneic oxygenation (AO) has been advocated to attenuate hypoxemia during endotracheal intubation (Pavlov et al., 2017).

The aim of this project was to assess for any knowledge deficits regarding AO among anesthesia providers and assess the willingness of these providers to include AO into their current practice. The project investigator conducted an education session involving the …

Plasma Resuscitation Attenuates Intestinal Barrier Disturbance Following Hemorrhagic Shock., Jessica E. Schucht

Electronic Theses and Dissertations

Background: Intestinal ischemia-reperfusion injury (IIRI) following resuscitated hemorrhagic shock (HS/RES) leads to endothelial damage, microcirculatory dysfunction and intestinal barrier breakdown, increasing intestinal permeability. This pathologic process contributes pathophysiology of multiple organ dysfunction syndrome (MODS) in some trauma patients. Although vascular smooth muscle machinery remains intact, microvascular vasoconstriction occurs secondary to endothelial cell damage, resulting in further ischemia and organ injury. Used separately, resuscitation with Fresh Frozen Plasma (FFP) or Direct Peritoneal Resuscitation (DPR) improves the intestinal microcirculation and alleviates organ injury. Further examination of these effects individually or combined could aid in the resuscitation of hemorrhagic shock. Methods: Sprague Dawley …

Epidemiology And Pathophysiology Of Common Skin Diseases In West Africa: An Immunodermatological Framework, Osazomon Imarenezor

All HCAS Student Capstones, Theses, and Dissertations

This capstone reviews the common skin diseases on a global scale. With these dermatoses being further funneled into Africa and then magnified into common West African dermatoses, the meta-analyses of literature available paints a clear picture of the epidemiological & pathological factors and their contribution to the skin disease. Each article analysed in this analysis was taken from a 20-year span of January 2000 to December 2019. The selection of articles was fine-tuned by identifying the distribution of skin disease, revealing the populations affected (age, gender, ethnicity, etc), the main causes, country of origin, the prognosis of disease, and the …

Corticotropin-Releasing Factor Infusion In The Bed Nucleus Of The Stria Terminalis Of Lactating Mice Alters Maternal Care And Induces Behavioural Phenotypes In Offspring, Kerstin Camile Creutzberg, Érika Kestering-Ferreira, Thiago Wendt Viola, Luis Eduardo Wearick-Silva, Rodrigo Orso, Bernardo Aguzzoli Heberle, Lucas Albrechet-Souza, Rosa Maria Martins De Almeida, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

The peripartum period is accompanied by numerous physiological and behavioural adaptations organised by the maternal brain. These changes are essential for adequate expression of maternal behaviour, thereby ensuring proper development of the offspring. The corticotropin-releasing factor (CRF) plays a key role in a variety of behaviours accompanying stress, anxiety, and depression. There is also evidence that CRF contributes to maladaptations during the peripartum period. We investigated the effects of CRF in the bed nucleus of the stria terminalis (BNST) of lactating mice during maternal care and analysed locomotor activity and anxiety-like behaviour in the offspring. The BNST has been implicated …

Neutrophil Signaling During Myocardial Infarction Wound Repair, Michael J. Daseke, Upendra Chalise, Mediha Becirovic-Agic, Jeffrey D. Salomon, Leah M. Cook, Adam J. Case, Merry L. Lindsey

Journal Articles: Cellular & Integrative Physiology

Neutrophils are key effector cells of the innate immune system, serving as a first line of defense in the response to injury and playing essential roles in the wound healing process. Following myocardial infarction (MI), neutrophils infiltrate into the infarct region to propagate inflammation and begin the initial phase of cardiac wound repair. Pro-inflammatory neutrophils release proteases to degrade extracellular matrix (ECM), a necessary step for the removal of necrotic myocytes as a prelude for scar formation. Neutrophils transition their phenotype over time to regulate MI inflammation resolution and stabilize scar formation. Neutrophils contribute to the evolution from inflammation to …

Characterization Of The 5′-Flanking Region Of The Human And Mouse Chac1 Genes, Yuki Nomura, Charity F. Sylvester, Lisa O. Nguyen, Mahmoud Kandeel, Yoko Hirata, Imran N. Mungrue, Kentaro Oh-Hashi

School of Medicine Faculty Publications

The Unfolded Protein Response pathway is a conserved signaling mechanism having important roles in cellular physiology and is perturbed accompanying disease. We previously identified the novel UPR target gene CHAC1, a direct target of ATF4, downstream of PERK-EIF2A and activated by the UPR pathway. CHAC1 enzyme directs catalysis of γ-linked glutamate bonds within specific molecular targets. CHAC1 is the first enzyme characterized that can catalyze intracellular glutathione degradation in eukaryotes, having implications for regulation of oxidative stress. DDIT3 (CHOP) is a terminal UPR transcription factor, regulated by ATF4 and an output promoting cell death signaling. Herein we examine the relationship …

Ace2 Mouse Models: A Toolbox For Cardiovascular And Pulmonary Research, Hongpeng Jia, Xinping Yue, Eric Lazartigues

School of Medicine Faculty Publications

Angiotensin-converting enzyme 2 (ACE2) has been identified as the host entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the COVID-19 pandemic. ACE2 is a regulatory enzyme of the renin-angiotensin system and has protective functions in many cardiovascular, pulmonary and metabolic diseases. This review summarizes available murine models with systemic or organ-specific deletion of ACE2, or with overexpression of murine or human ACE2. The purpose of this review is to provide researchers with the genetic tools available for further understanding of ACE2 biology and for the investigation of ACE2 in the pathogenesis and treatment of COVID-19.