Digital Commons Network^™

Proteolipid Protein 1 Regulates Inflammation In The Central Nervous System, Whitney Hoff

Wayne State University Theses

Pelizaeus-Merzbacher disease (PMD) results from mutations in the proteolipid protein 1 (PLP1) gene including PLP1 duplications and deletions. The absence of PLP is preferable to PLP1/Plp1 duplication in PMD patients and rodents as lifespan of PLP1/Plp1 null mammals is nearly normal. The reason for this is not entirely understood. However, because of this, less attention has been placed on Plp1 null mutations than on classical PMD mutations. However, data show that PLP levels must be properly titrated to ensure normal brain function. Specifically, changes in PLP1/Plp1 expression can result in massive microglia activation in animal models of PMD and likely …

Role Of Oxidized Extracellular Vesicles As Early Biomarkers And Inflammatory Mediators In Chemotherapy-Induced Normal Tissue Injury, Chontida Yarana

Theses and Dissertations--Toxicology and Cancer Biology

Significant advances in the efficacy of cancer therapy have been accompanied by an escalation of side effects that result from therapy-induced injury to normal tissues. Patients with high grade cancer or metastasis are often treated with chemotherapy, 50% of which are associated with reactive oxygen species generation and cellular oxidative stress. Heart is the normal tissue most susceptible to chemotherapy-induced oxidative stress and heart disease is the most common leading cause of death in cancer survivors. However, early and sensitive biomarkers to identify heart disease are still lacking. Extracellular vesicles (EVs) are released from cells during oxidative stress and send …

The Brazelton Neonatal Behavioral Assessment Scale: A Validity And Reliability Study In A Turkish Sample, Öznur Başdaş, Emi̇ne Erdem, Ferhan Elmali, Seli̇m Kurtoğlu

Turkish Journal of Medical Sciences

Background/aim: The aim of the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) is to gather a comprehensive pro le of neonatal functioning by describing the full range of neonatal behavior, including competencies and strengths, as well as di culties or deviations. is instrument has proved to be of great clinical value by detecting infants at risk for later developmental problems. is work was conducted methodologically with the aim of a Turkish validity and reliability study of the BNBAS. Materials and methods: The study was conducted in a large tertiary hospital in Turkey. After establishing content and language validity, the BNBAS was …

Comparison Between Iloprost And Alprostadil For Protection Againstischemia/Reperfusion Injury In A Rat Model, Deni̇z Çevi̇rme, Taylan Adademi̇r, Eylül Kafali Başaran, Ömer Faruk Şavluk, Ahmet Eli̇bol, Gözde Erkanli Şentürk, Hati̇ce Akkaya, Bayram Yilmaz

Turkish Journal of Medical Sciences

Background/aim: Alprostadil and iloprost are successful agents used for both pulmonary hypertension and extremity ischemia treatment. Different systemic effects of these agents may change the preferences of clinical usage. Superiority of preventing ischemia/ reperfusion (IR) injury is a criterion for clinical preference of these agents. The present study was designed to compare the protective effects of alprostadil and iloprost in a rat model of IR injury. Materials and methods: Twenty-three male Sprague Dawley rats were used (aged 8-12 weeks, mean weight 230 ± 30 g). They were randomized into 4 groups: Group 1 (iloprost + IR), Group 2 (alprostadil + …

Complete Genome Sequence Of Moraxella Bovis Strain Epp-63 (300), An Etiologic Agent Of Infectious Bovine Keratoconjunctivitis, John Dustin Loy, Aaron M. Dickey, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

We report here the complete closed genome sequence of Moraxella bovis strain Epp-63 (300) (Epp63). This strain was isolated from an infectious bovine keratoconjunctivitis (IBK) case in 1963. Since then, Epp63 has been used extensively for IBK research. Consequently, the genome sequence of Epp63 should help elucidate IBK host-pathogen interactions.

Non-Invasive Mitochondrial Modulation With Near-Infrared Light Reduces Brain Injury After Stroke, Christos Dionisos Strubakos

Wayne State University Dissertations

Acute ischemic stroke is a debilitating disease that causes significant brain injury.

While rapid restoration of blood flow is critical to salvage the ischemic brain, reperfusion

of tissue can further drive brain damage by inducing generation of mitochondrial reactive

oxygen species (Chouchani et al., 2014a). Recent studies by our group found that noninvasive

mitochondrial modulation (NIMM) with near-infrared (NIR) light can limit the

production of reactive oxygen species following global brain ischemia (T. H. Sanderson

et al., 2018). NIR interacts with the rate limiting step of the mitochondrial electron

transport chain (ETC), cytochrome c oxidase (COX), and modulates mitochondrial

respiration. …

Transport Of Bmaa Into Neurons And Astrocytes By System XC-, Rebecca Albano, Doug Lobner

Biomedical Sciences Faculty Research and Publications

The study of the mechanism of β-N-methylamino-l-alanine (BMAA) neurotoxicity originally focused on its effects at the N-methyl-d-aspartate (NMDA) receptor. In recent years, it has become clear that its mechanism of action is more complicated. First, there are certain cell types, such as motor neurons and cholinergic neurons, where the dominate mechanism of toxicity is through action at AMPA receptors. Second, even in cortical neurons where the primary mechanism of toxicity appears to be activation of NMDA receptors, there are other mechanisms involved. We found that along with NMDA receptors, activation of mGLuR5 receptors and effects on the …

What Does The Fos Say? Using Fos-Based Approaches To Understand The Contribution Of Stress To Substance Use Disorders, Jayme R. Mcreynolds, John P. Christianson, Jordan M. Blacktop, John Mantsch

Biomedical Sciences Faculty Research and Publications

Despite extensive research efforts, drug addiction persists as a largely unmet medical need. Perhaps the biggest challenge for treating addiction is the high rate of recidivism. While many factors can promote relapse in abstinent drug users, the contribution of stress is particularly problematic, as stress is uncontrollable and pervasive in the lives of those struggling with addiction. Thus, understanding the neurocircuitry that underlies the influence of stress on drug seeking is critical for guiding treatment. Preclinical research aimed at defining this neurocircuitry has, in part, relied upon the use of experimental approaches that allow visualization of cellular and circuit activity …

17Β-Estradiol Potentiates The Reinstatement Of Cocaine Seeking In Female Rats: Role Of The Prelimbic Prefrontal Cortex And Cannabinoid Type-1 Receptors, Elizabeth M. Doncheck, Luke A. Urbanik, Margot C. Debaker, Laura M. Barron, Gage T. Liddiard, Jennifer J. Tuscher, Karyn M. Frick, Cecilia J. Hillard, John Mantsch

Biomedical Sciences Faculty Research and Publications

Clinical observations imply that female cocaine addicts experience enhanced relapse vulnerability compared with males, an effect tied to elevated estrogen phases of the ovarian hormone cycle. Although estrogens can enhance drug-seeking behavior, they do not directly induce reinstatement on their own. To model this phenomenon, we tested whether an estrogen could augment drug-seeking behavior in response to an ordinarily subthreshold reinstatement trigger. Following cocaine self-administration and extinction, female rats were ovariectomized to isolate estrogen effects on reinstatement. Although neither peak proestrus levels of the primary estrogen 17β-estradiol (E2; 10 μg/kg, i.p., 1-h pretreatment) nor a subthreshold cocaine dose …

Mechanotransduction Signaling In Podocytes From Fluid Flow Shear Stress., Tarak Srivastava, Hongying Dai, Daniel P. Heruth, Uri S. Alon, Robert E. Garola, Jianping Zhou, R Scott Duncan, Ashraf El-Meanawy, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Recently, we and others have found that hyperfiltration-associated increase in biomechanical forces, namely, tensile stress and fluid flow shear stress (FFSS), can directly and distinctly alter podocyte structure and function. The ultrafiltrate flow over the major processes and cell body generates FFSS to podocytes. Our previous work suggests that the cyclooxygenase-2 (COX-2)-PGE2-PGE2 receptor 2 (EP2) axis plays an important role in mechanoperception of FFSS in podocytes. To address mechanotransduction of the perceived stimulus through EP2, cultured podocytes were exposed to FFSS (2 dyn/cm2) for 2 h. Total RNA from cells at the end of FFSS treatment, 2-h post-FFSS, and 24-h …

Intra-Arterial Nitroglycerin As Directed Acute Treatment In Experimental Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Rebecca Trueman, Annastazia E. Learoyd, Amanda A. Gorman, Justin F. Fraser, Gregory J. Bix

Neuroscience Faculty Publications

BACKGROUND: Nitroglycerin (also known as glyceryl trinitrate (GTN)), a vasodilator best known for treatment of ischemic heart disease, has also been investigated for its potential therapeutic benefit in ischemic stroke. The completed Efficacy of Nitric Oxide in Stroke trial suggested that GTN has therapeutic benefit with acute (within 6 hours) transdermal systemic sustained release therapy.

OBJECTIVE: To examine an alternative use of GTN as an acute therapy for ischemic stroke following successful recanalization.

METHODS: We administered GTN IA following transient middle cerebral artery occlusion in mice. Because no standard dose of GTN is available following emergent large vessel occlusion, we …

Disturbance Of Redox Homeostasis In Down Syndrome: Role Of Iron Dysmetabolism, Eugenio Barone, Andrea Arena, Elizabeth Head, D. Allan Butterfield, Marzia Perluigi

Sanders-Brown Center on Aging Faculty Publications

Down syndrome (DS) is the most common genetic form of intellectual disability that leads in the majority of cases to development of early-onset Alzheimer-like dementia (AD). The neuropathology of DS has several common features with AD including alteration of redox homeostasis, mitochondrial deficits, and inflammation among others. Interestingly, some of the genes encoded by chromosome 21 are responsible of increased oxidative stress (OS) conditions that are further exacerbated by decreased antioxidant defense. Previous studies from our groups showed that accumulation of oxidative damage is an early event in DS neurodegeneration and that oxidative modifications of selected proteins affects the integrity …

Can Nox1 Activity Initiate Parkinson's-Like Pathology In An Enteroendocrine Cell Line?, Evan Adler

Honors Undergraduate Theses

Increased attention has been given to the gut lately in a number of conditions, from maintaining health via the use of probiotics to treating Autism Spectrum Disorder. Parkinson's Disease has a history with the gut starting with the Braak hypothesis, in which eminent researcher Heiko Braak observed that the spread of Parkinson's (PD) seemed to occur along either olfactory or enteric neurons prior to reaching the substantia nigra in the midbrain, where the classical disease symptoms become evident. Though this finding was largely ignored at the time, the possibility of a gut origin for PD has received interest lately as …

Development Of A Non-Human Primate Model For Staphylococcus Aureus Nasal Carriage, Amanda Lasseter

Electronic Theses and Dissertations

Staphylococcus aureus nasal carriage (SANC) is largely asymptomatic, but presents a risk of autoinfection and dissemination to new immunocompromised hosts. SA disease states range from mild cutaneous infections to life-threatening bacteremia. Historically utilized rodent models do not naturally carry SA in the nose, are insufficient in longitudinal SANC experimentation, and lack immune factors that are vital in human clearance of SA. The nasal passages of non-human primates are similar anatomically and histologically, and reproductive mucosal studies have shown similar immune responses to pathogens and human-relevant microbial profiles. Seventeen captive pigtailed macaques (Macaca nemestrina) were found to naturally carry SA in …

Embryonic Stem Cell Derived Exosomes Enhance Cardiac Stem Cell Differentiation Into Heart Cells, Jamillah Hammond

Electronic Theses and Dissertations

Transplantation of embryonic stem (ES) cells into the ischemic and infarcted heart has proven to repopulate cardiac cell populations, attenuate structural cardiac remodeling, and rescue cardiac function. Unfortunately, the pluripotency of ES cells increases risk of teratoma formation in vivo. Exosomes, smaller in comparison to ES cells, are cell free carriers of miRNA, proteins, and lipids, and do not suggest risk of teratoma formation. Exosomes have been proposed to mediate and attenuate regeneration following myocardial infarction (MI), however, the role of exosomes derived from ES cells (ES-Exo) in activating resident cardiac stem cells (CSCs) to undergo cardiac differentiation is not …

Repaglinide Inhibits Cyclosporine A-Induced Renal Tubular Toxicityby Affecting Apoptosis And Bax And Bcl-2 Expression, Jin Li, Hui Li, Qi Xiong Li, Ying Xue

Turkish Journal of Medical Sciences

Background/aim: Repaglinide (RG) is a prandial glucose regulator used for the treatment of type 2 diabetes. Our recent study showed that RG plays an important role in cyclosporine A (CsA)-induced nephrotoxicity through its antioxidant properties. However, it is not known whether or not RG has any protective effect on CsA-induced renal tubular toxicity by affecting apoptosis and expression of apoptosis-associated protein. The purpose of this study was to investigate the effects of RG on CsA-induced renal tubule apoptosis and Bax and Bcl-2 protein expression in rats. Materials and methods: Forty male Sprague Dawley rats weighing 250-300 g were randomly divided …

The Role Of Pro-Inflammatory Mediators Ifnβ And Prostaglandin E2 In Suppression Of Innate Immunity To Listeria Monocytogenes, Michelle G. Pitts

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

As a foodborne pathogen, Listeria monocytogenes (Lm) encounters many barriers to invasion and dissemination in the host that may change the nature of host response. Lm has been most commonly studied using intravenous (i.v.) inoculation, however, a method that delivers a bolus of bacteria directly to the bloodstream. Thus, little is known about what systemic and local mediators are triggered during the natural course of infection and how these may impact susceptibility. Our laboratory used foodborne transmission of Lm in mice to assess whether the method of transmission and the specific organ microenvironment could affect infection-induced secretion of …

Studying Vascular Morphologies In The Aged Human Brain Using Large Autopsy Datasets, Eseosa T. Ighodaro

Theses and Dissertations--Neuroscience

Cerebrovascular disease is a major cause of dementia in elderly individuals, especially Black/African Americans. Within my dissertation, we focused on two vascular morphologies that affect small vessels: brain arteriolosclerosis (B-ASC) and multi-vascular profiles (MVPs). B-ASC is characterized by degenerative thickening of the wall of brain arterioles. The risk factors, cognitive sequelae, and co-pathologies of B-ASC are not fully understood. To address this, we used multimodal data from the National Alzheimer’s Coordinating Center, Alzheimer’s Disease Neuroimaging Initiative, and brain-banked tissue samples from the University of Kentucky Alzheimer’s Disease Center (UK-ADC) brain repository. We analyzed two age at death groups separately: < 80 years and ≥ 80 years. Hypertension was a risk factor in the < 80 years at death group. In addition, an ABCC9 …