Life Sciences Commons^™

Chronic Stress-Induced Neuroinflammation: Relevance Of Rodent Models To Human Disease., Abigail G White, Elias Elias, Andrea Orozco, Shivon A Robinson, Melissa T Manners

Faculty Scholarship for the College of Science & Mathematics

The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress-a …

Identification Of Lipids And Cytokines In Plasma And Follicular Fluid Before And After Follicle-Stimulating Hormone Stimulation As Potential Markers For Follicular Maturation In Cattle, Alexandria P. Snider, Renata S. Gomes, Adam F. Summers, Sarah C. Tenley, Mohamed A. Abedal-Majed, Renee M. Mcfee, Jennifer R. Wood, John S. Davis, Andrea S. Cupp

Department of Animal Science: Faculty Publications

The process of follicle maturation leading to ovulation is a key milestone in female fertility. It is known that circulating lipids and cytokines play a role in the follicle’s ability to go through follicular maturation and the ovulatory processes. However, the specific mechanisms are not well understood. We posit that dysregulation of granulosa cells influences the ovarian environment, which tries to adapt by changing released lipids and cytokines to achieve follicular maturation. Eleven non-lactating adult females underwent estrus synchronization with two injections of PGF2 14 days apart. Daily blood samples were collected for 28 days to monitor steroid hormone production …

Cytokine Data For Cytokine Profile Assessment From Peruvian Pinniped (Arctocephalus Australis And Otaria Byronia) Plasma, Mykenzee Munaco, Milton Levin, Michael Adkesson, Susana Cárdenas-Alayzad, Dimitrios G. Giarikos, Amy C. Hirons

SECLER Data

Large colonies of two vulnerable, sympatric pinniped species, Peruvian fur seals (Arctocephalus australis Peruvian subpopulation; PFS) and South American sea lions (Otaria byronia; SASL), reside and reproduce in Punta San Juan, Peru (PSJ) where they are exposed to stressors such as contaminants and El Niño Southern Oscillation (ENSO) events. The use of cytokines as immune biomarkers can be indicative of an animal’s health and function by allowing for the assessment of an individual's cytokine balance as type I helper T cells (Th1) or type II helper T cells (Th2) dominant. Utilizing archived pinniped plasma samples from 2009-2019 …

Effects Of Fucoidan Supplementation On Inflammatory And Immune Response After High-Intensity Exercise, Bridget A. Mcfadden, Caroline S. Vincenty, Alexa J. Chandler, Harry P. Cintineo, Blaine S. Lints, Gianna F. Mastrofini, Shawn M. Arent

Faculty Scholarship

Introduction: High-intensity exercise (HIE) can damage the musculotendon complex and impact the immune response, resulting in post-exercise inflammation. Sufficient rest and recovery will improve muscular resilience against future damaging bouts; however, HIE with minimal durations of rest is common in athletic competitions that facilitate persistent inflammation and immune dysregulation. Fucoidans are fucose-rich sulfated polysaccharides with demonstrated anti-inflammatory and pro-immune responses. Fucoidans may improve inflammation and immune responses, which may prove beneficial for individuals who regularly engage in repeated HIE. The research purpose was to investigate the safety and efficacy of fucoidans on inflammatory and immune markers following HIE.

Methods …

Low-Salt Diet Reduces Anti-Ctla4 Mediated Systemic Immune-Related Adverse Events While Retaining Therapeutic Efficacy Against Breast Cancer, Durga Khandekar, Debolanle O. Dahunsi, Isaac V. Manzanera Esteve, Sonya Reid, Jeffrey C. Rathmell, Jens M. Titze, Venkataswarup Tiriveedhi

Biology Faculty Research

Immune checkpoint inhibitor (ICI) therapy has revolutionized the breast cancer treatment landscape. However, ICI-induced systemic inflammatory immune-related adverse events (irAE) remain a major clinical challenge. Previous studies in our laboratory and others have demonstrated that a high-salt (HS) diet induces inflammatory activation of CD4+T cells leading to anti-tumor responses. In our current communication, we analyzed the impact of dietary salt modification on therapeutic and systemic outcomes in breast-tumor-bearing mice following anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibody (mAb) based ICI therapy. As HS diet and anti-CTLA4 mAb both exert pro-inflammatory activation of CD4+T cells, we hypothesized that a combination of …

Effects Of Glucocorticoids Upon Pro-Inflammatory Responses To Acute Sleep Fragmentation, Hunter Weaver

Masters Theses & Specialist Projects

Sleep loss is a common problem in humans who suffer from obstructive sleep apnea. Sleep aids in the regulation of immune responses, some of which induce inflammatory responses. Cytokines regulate the inflammatory process and are released in response to sleep fragmentation (SF) in mice. Glucocorticoids are hormones that are released from the adrenal cortices during a stress response and are considered to be anti-inflammatory and immunosuppressive at high doses but may stimulate immune function on an acute level. The first hypothesis tested was that normal physiological expression of glucocorticoids (Sham) will display increased IL-1β and TNFα expression levels, while high …

Molecular Approaches For The Validation Of The Baboon As A Nonhuman Primate Model For The Study Of Zika Virus Infection, Emma Mask, V. L. Hodara, Jessica E. Callery, L. M. Parodi, V. Obregon-Perko, S. Yagi, J. Glenn, P. Frost, E. Clemmons, J. L. Patterson, L. A. Cox, Luis D. Giavedoni

Biology Faculty Research

Nonhuman primates (NHP) are particularly important for modeling infections with viruses that do not naturally replicate in rodent cells. Zika virus (ZIKV) has been responsible for sporadic epidemics, but in 2015 a disseminated outbreak of ZIKV resulted in the World Health Organization declaring it a global health emergency. Since the advent of this last epidemic, several NHP species, including the baboon, have been utilized for modeling and understanding the complications of ZIKV infection in humans; several health issues related to the outcome of infection have not been resolved yet and require further investigation. This study was designed to validate, in …

Therapeutic Treatment With The Anti-Inflammatory Drug Candidate Mw151 May Partially Reduce Memory Impairment And Normalizes Hippocampal Metabolic Markers In A Mouse Model Of Comorbid Amyloid And Vascular Pathology, David J. Braun, David K. Powell, Christopher J. Mclouth, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Neuroscience Faculty Publications

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, but therapeutic options are lacking. Despite long being able to effectively treat the ill-effects of pathology present in various rodent models of AD, translation of these strategies to the clinic has so far been disappointing. One potential contributor to this situation is the fact that the vast majority of AD patients have other dementia-contributing comorbid pathologies, the most common of which are vascular in nature. This situation is modeled relatively infrequently in basic AD research, and almost never in preclinical studies. As part of our efforts to develop …

An Artifact In Intracellular Cytokine Staining For Studying T Cell Responses And Its Alleviation., Zheng Gong, Qing Li, Jiayuan Shi, Guangwen Ren

Faculty Research 2022

Intracellular cytokine staining (ICS) is a widely employed ex vivo method for quantitative determination of the activation status of immune cells, most often applied to T cells. ICS test samples are commonly prepared from animal or human tissues as unpurified cell mixtures, and cell-specific cytokine signals are subsequently discriminated by gating strategies using flow cytometry. Here, we show that when ICS samples contain Ly6G⁺ neutrophils, neutrophils are ex vivo activated by an ICS reagent - phorbol myristate acetate (PMA) - which leads to hydrogen peroxide (H₂O₂) release and death of cytokine-expressing T cells. This artifact …

Inflammatory Mediation Of Heat Stress-Induced Growth Deficits In Livestock And Its Potential Role As A Target For Nutritional Interventions: A Review, Micah S. Most, Dustin T. Yates

Department of Animal Science: Faculty Publications

Heat stress is detrimental to well-being and growth performance in livestock, and systemic inflammation arising during chronic heat stress contributes to these poor outcomes. Sustained exposure of muscle and other tissues to inflammation can impair the cellular processes that facilitate muscle growth and intramuscular fat deposition, thus reducing carcass quality and yield. Climate change is expected to produce more frequent extreme heat events, increasing the potential impact of heat stress on sustainable livestock production. Feedlot animals are at particularly high risk for heat stress, as confinement limits their ability to seek cooling from the shade, water, or breeze. Economically practical …

Proteomics-Derived Basal Biomarker Dna-Pkcs Is Associated With Intrinsic Subtype And Long-Term Clinical Outcomes In Breast Cancer, Karama Asleh, Nazia Riaz, Angela S. Cheng, Dongxia Gao, Samuel C Y. Leung, Meenakshi Anurag, Torsten O. Nielsen

Centre for Regenerative Medicine & Stem Cell Research

Precise biomarkers are needed to guide better diagnostics and therapeutics for basal-like breast cancer, for which DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has been recently reported by the Clinical Proteomic Tumor Analysis Consortium as the most specific biomarker. We evaluated DNA-PKcs expression in clinically-annotated breast cancer tissue microarrays and correlated results with immune biomarkers (training set: n = 300; validation set: n = 2401). Following a pre-specified study design per REMARK criteria, we found that high expression of DNA-PKcs was significantly associated with stromal and CD8 + tumor infiltrating lymphocytes. Within the basal-like subtype, tumors with low DNA-PKcs and high …

Bioactive Recombinant Human Oncostatin M For Nmr-Based Screening In Drug Discovery, Olga A. Mass, Joseph Tuccinardi, Luke Woodbury, Cody L. Wolf, Bri Grantham, Kelsey Holdaway, Xinzhu Pu, Matthew D. King, Don L. Warner, Cheryl L. Jorcyk, Lisa R. Warner

Biomolecular Research Center Publications and Presentations

Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure …

Biomarkers For Impending Risk Of Osteoporosis In Premenopausal Women, Rehana Rehman, Ali Usman, Aisha Sheikh, Rozeena Baig

Department of Biological & Biomedical Sciences

Objective: To compare 'cytokines' and 'bone turnover markers' in pre- and post-menopausal women and identify their relationship with bone mineral density (BMD) in both groups. Study Design: A cross-sectional study.
Place and duration of study: Department of Biological & Biomedical Sciences, The Aga Khan University, Karachi, Pakistan, from June 2017 to August 2019.
Methodology: Groups comprised of healthy premenopausal and postmenopausal women from the general population belonging to different ethnic groups and socio-economic status. Serum cytokines and bone turnover markers were assessed by solid-phase immunoassays, BMD (gm /cm2)] measurement was performed by dual-energy X-ray absorptiometry at the hip, lumbar spine, …

Cancer Salt Nostalgia, Aashish S. Allu, Venkataswarup Tiriveedhi

Biology Faculty Research

High-salt (sodium chloride) diets have been strongly associated with disease states and poor health outcomes. Traditionally, the impact of salt intake is primarily studied in cardiovascular diseases, hypertension and renal diseases; however, recently there has been increasing evidence demonstrating the role of salt in autoimmune diseases. Salt has been shown to modulate the inflammatory activation of immune cells leading to chronic inflammation-related ailments. To date, there is minimal evidence showing a direct correlation of salt with cancer incidence and/or cancer-related adverse clinical outcomes. In this review article, we will discuss the recent understanding of the molecular role of salt, and …

Sickness Behaviors Across Vertebrate Taxa: Proximate And Ultimate Mechanisms, Patricia C. Lopes, Susannah S. French, Douglas C. Woodhams, Sandra A. Binning

Biology Faculty Publications

There is nothing like a pandemic to get the world thinking about how infectious diseases affect individual behavior. In this respect, sick animals can behave in ways that are dramatically different from healthy animals: altered social interactions and changes to patterns of eating and drinking are all hallmarks of sickness. As a result, behavioral changes associated with inflammatory responses (i.e. sickness behaviors) have important implications for disease spread by affecting contacts with others and with common resources, including water and/or sleeping sites. In this Review, we summarize the behavioral modifications, including changes to thermoregulatory behaviors, known to occur in vertebrates …

Sickness Behaviors Across Vertebrate Taxa: Proximate And Ultimate Mechanisms, Patricia C. Lopes, Susannah S. French, Douglas C. Woodhams, Sandra A. Binning

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

There is nothing like a pandemic to get the world thinking about how infectious diseases affect individual behavior. In this respect, sick animals can behave in ways that are dramatically different from healthy animals: altered social interactions and changes to patterns of eating and drinking are all hallmarks of sickness. As a result, behavioral changes associated with inflammatory responses (i.e. sickness behaviors) have important implications for disease spread by affecting contacts with others and with common resources, including water and/or sleeping sites. In this Review, we summarize the behavioral modifications, including changes to thermoregulatory behaviors, known to occur in vertebrates …

Placenta-Expanded Stromal Cell Therapy In A Rodent Model Of Simulated Weightlessness, Amber M. Paul, Linda Rubinstein, Charles Houseman, Metadel Abegaz, Steffy Tabares Ruiz

Publications

Long duration spaceflight poses potential health risks to astronauts during flight and re-adaptation after return to Earth. There is an emerging need for NASA to provide successful and reliable therapeutics for long duration missions when capability for medical intervention will be limited. Clinically relevant, human placenta-derived therapeutic stromal cells (PLX-PAD) are a promising therapeutic alternative. We found that treatment of adult female mice with PLX-PAD near the onset of simulated weightlessness by hindlimb unloading (HU, 30 d) was well-tolerated and partially mitigated decrements caused by HU. Specifically, PLX-PAD treatment rescued HU-induced thymic atrophy, and mitigated HU-induced changes in percentages of …

Ex Vivo High Salt Activated Tumor-Primed Cd4+T Lymphocytes Exert A Potent Anti-Cancer Response, Venkataswarup Tiriveedhi, Michael Ivy, Elbert L. Myles, Roy Zent, Jeffrey C. Rathmell, Jens M. Titze

Biology Faculty Research

Cell based immunotherapy is rapidly emerging as a promising cancer treatment. A modest increase in salt (sodium chloride) concentration in immune cell cultures is known to induce inflammatory phenotypic differentiation. In our current study, we analyzed the ability of salt treatment to induce ex vivo expansion of tumor-primed CD4 (cluster of differentiation 4)+T cells to an effector phenotype. CD4+T cells were isolated using immunomagnetic beads from draining lymph nodes and spleens from tumor bearing C57Bl/6 mice, 28 days post-injection of Py230 syngeneic breast cancer cells. CD4+T cells from non-tumor bearing mice were isolated from splenocytes of 12-week-old C57Bl/6 mice. These …

A Literature Review On Tumor Microenvironmental Immunosuppressive Mechanisms On Cd8+ T Lymphocytes That Contribute To Tumor Immune Evasion, Jessica R. Gabrysiak

Honors Projects

The concept of tumor immune evasion is a prevalent obstacle in cancer research and the development of immunotherapies. Increased insight into mechanisms that are responsible for the escape of cancer cells from the immune system will help to improve therapeutic approaches and provide understanding into slowing disease progression by utilizing the body's immune system. With immunotherapy development on the forefront of cancer research due to seemingly attenuated toxicity and resistance when compared to traditional chemoradiotherapy, analyzing these obstacles is essential for emerging roles and future directions in the discipline of immuno-oncology. Understanding the immunosuppressive molecules that contribute to the process …

Cytokine And Haptoglobin Profiles From Shipping Through Sickness And Recovery In Metaphylaxis- Or Un-Treated Cattle, Carol G. Chitko-Mckown, Gary L. Bennett, Larry A. Kuehn, Keith D. Dedonder, Michael D. Apley, Gregory P. Harhay, Michael L. Clawson, Aspen M. Workman, Bradley J. White, Robert L. Larson, Sarah F. Capik, Brian V. Lubbers

Roman L. Hruska U.S. Meat Animal Research Center: Reports

Fifty-six head of cattle, 28 animals with bovine respiratory disease complex (BRDC), and 28 healthy animals that were matched by treatment, sale barn of origin, day, and interactions among these variables, were identified from a population of 180 animals (60 each purchased at three sale barns located in Missouri, Tennessee, and Kentucky) enrolled in a study comparing animals receiving metaphylaxis to saline-treated controls. Cattle were transported to a feedlot in KS and assigned to treatment group. Blood samples were collected at Day 0 (at sale barn), Day 1, Day 9, and Day 28 (at KS feedlot), and transported to the …

Nutrition And Chronic Pain, Elise Withers, Mateja R. Savoie-Roskos, Riley Samples, Maren Wright Voss

All Current Publications

The internet is full of information about anti-inflammatory diets, foods, and supplements claiming to prevent or alleviate chronic pain. For those who struggle with chronic pain, sound dietary advice is essential to improve intake and ultimately decrease pain (Arranz et al., 2010). However, it’s important to note that research showing the impact of specific foods on health and the immune system is currently limited; therefore, these claims should be interpreted with caution (Elma et al., 2020; Harvard Health, 2018). This fact sheet will cover (1) how inflammation affects chronic pain and (2) how eating a well-balanced diet may help reduce …

Effect Of Acute Sleep Fragmentation Upon Inflammatory Response Of Brown And White Adipose Tissue In Male Mice, Zach Wriedt

Mahurin Honors College Capstone Experience/Thesis Projects

Sleep is an important process required for vertebrates, including humans, to function. When sleep is disrupted, it leads to deleterious effects such as inflammatory responses throughout the body. Past studies have shown that acute (24 h) sleep fragmentation (SF) leads to an inflammatory response in white adipose tissue. However, whether brown adipose tissue responds in a similar fashion is unknown. Male adult (>8 weeks of age) C57BL/6j mice were subjected to SF for 24 h using a cage outfitted with a bar that moves horizontally across the cage every 2 min to periodically awaken mice (N =10). Controls were …

The Effect Of Age On Neurological Inflammation To Acute Sleep Fragmentation In Mice, Molly Taylor

Mahurin Honors College Capstone Experience/Thesis Projects

Obstructive sleep apnea is identified by recurring events of airway collapse during sleep, intermittent hypoxia, and perturbations in sleep continuity, known as sleep fragmentation. There is evidence to suggest that elderly patients are more at risk of developing obstructive sleep apnea. The purpose of this study was to assess whether age affects neurological inflammatory responses to acute sleep fragmentation. This assessment was made by subjecting young (4-5 months old) and old (10-11 months old) male C57BL/6j mice to automated sleep fragmentation, as well as having mice in both age categories as a control with no sleep fragmentation, for twenty-four hours. …

Complex Tissue Regeneration In Mammals Is Associated With Reduced Inflammatory Cytokines And An Influx Of T Cells, Thomas R. Gawriluk, Jennifer Simkin, Corin K. Hacker, John M. Kimani, Stephen G. Kiama, Vanessa O. Ezenwa, Ashley W. Seifert

Biology Faculty Publications

While mammals tend to repair injuries, other adult vertebrates like salamanders and fish regenerate damaged tissue. One prominent hypothesis offered to explain an inability to regenerate complex tissue in mammals is a bias during healing toward strong adaptive immunity and inflammatory responses. Here we directly test this hypothesis by characterizing part of the immune response during regeneration in spiny mice (Acomys cahirinus and Acomys percivali) vs. fibrotic repair in Mus musculus. By directly quantifying cytokines during tissue healing, we found that fibrotic repair was associated with a greater release of pro-inflammatory cytokines (i.e., IL-6, CCL2, and CXCL1) …

Porcine Cytokines, Chemokines And Growth Factors: 2019 Update, Harry D. Dawson, Yongming Sang, Joan K. Lunney

Agricultural and Environmental Sciences Faculty Research

Pigs are a major food source worldwide as well as major biomedical models for human physiology and therapeutics. A thorough understanding of porcine immunity is essential to prevent and treat infectious diseases, and develop effective vaccines and therapeutics. The use of pigs as biomedical models is dependent on the growing molecular and immune toolbox. This paper summarizes current knowledge of swine cytokines, chemokines and growth factors, identifying 289 pig proteins, characterizing knowledge of their gene structures and families. It identifies areas in the current swine genome build that need to be clarified. A broad-based literature and vendor search was conducted …

Recombinant Human Proteoglycan-4 Mediates Interleukin-6 Response In Both Human And Mouse Endothelial Cells Induced Into A Sepsis Phenotype, Holly A. Richendrfer, Mitchell M. Levy, Khaled A. Elsaid, Tannin A. Schmidt, Ling Zhang, Ralph Cabezas, Gregory D. Jay

Pharmacy Faculty Articles and Research

Objectives:

Sepsis is a leading cause of death in the United States. Putative targets to prevent systemic inflammatory response syndrome include antagonism of toll-like receptors 2 and 4 and CD44 receptors in vascular endothelial cells. Proteoglycan-4 is a mucinous glycoprotein that interacts with CD44 and toll-like receptor 4 resulting in a blockade of the NOD-like receptor pyrin domain-containing-3 pathway. We hypothesized that endothelial cells induced into a sepsis phenotype would have less interleukin-6 expression after recombinant human proteoglycan 4 treatment in vitro.

Design:

Enzyme-linked immunosorbent assay and reverse transcriptase-quantitative polymerase chain reaction to measure interleukin-6 protein and gene expression.

Setting: …

Influence Of Total Western Diet On Docosahexaenoic Acid Suppression Of Silica-Triggered Lupus Flaring In Nzbwf1 Mice, Kristen N. Gilley, Kathryn A. Wierenga, Preeti S. Chauhaun, James G. Wagner, Ryan P. Lewandowski, Elizbeth A. Ross, A. L. Lock, Jack R. Harkema, Abby D. Benninghoff, James J. Pestka

Animal, Dairy, and Veterinary Science Faculty Publications

Lupus is a debilitating multi-organ autoimmune disease clinically typified by periods of flare and remission. Exposing lupus-prone female NZBWF1 mice to crystalline silica (cSiO₂), a known human autoimmune trigger, mimics flaring by inducing interferon-related gene (IRG) expression, inflammation, ectopic lymphoid structure (ELS) development, and autoantibody production in the lung that collectively accelerate glomerulonephritis. cSiO₂-triggered flaring in this model can be prevented by supplementing mouse diet with the ω-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). A limitation of previous studies was the use of purified diet that, although optimized for rodent health, does not reflect the …

Can Unconventional Immunomodulatory Agents Help Alleviate Covid-19 Symptoms And Severity?, Stephen W. Mamber, Steven Krakowka, Jeffrey L. Osborn, Lloyd Saberski, Ryan G. Rhodes, Albert E. Dahlberg, Sunthorn Pond-Tor, Kara Fitzgerald, Neal Wright, Sarah Beseme, John Mcmichael

Biology Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce increased levels of a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin-1 (IL-1), IL-6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes the following four unconventional but …

Tumor Necrosis Factor-Alpha Signaling May Contribute To Chronic West Nile Virus Post-Infectious Proinflammatory State, A. Arturo Leis, Marie F. Grill, Brent P. Goodman, Syed B. Sadiq, David J. Sinclair, Parminder J.S. Vig, Fengwei Bai

Faculty Publications

Background: West Nile virus (WNV) causes a spectrum of human disease ranging from a febrile illness (WNV fever) to severe neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis). Since WNV gained entry into North America in 1999, clinicians caring for WNV survivors have observed persistent neurological symptoms occurring long-after the production of neutralizing antibodies and clearance of the virus. Accordingly, alternative pathogeneses other than direct viral invasion have been hypothesized to explain these post-infectious symptoms. The dominant hypothesis is that antiviral inflammatory responses triggered initially to clear WNV may persist to promote a post-infectious proinflammatory state.

Methods: In 4 serologically-confirmed …

Effects Of Alpha- And Beta-Adrenergic Receptor Blockade Upon Inflammatory Responses To Acute And Chronic Sleep Fragmentation, Nicholas David Wheeler

Masters Theses & Specialist Projects

Generally, sleep is viewed as a recuperative process and its dysregulation has

cognitive, metabolic, immunological, and inflammatory implications that are largely deleterious to human health. Epidemiological and empirical studies have suggested that sleep fragmentation (SF) as result of obstructive sleep apnea (OSA) and other sleep abnormalities leads to pronounced systemic inflammatory responses, which are influenced by the sympathetic nervous system (SNS). However, the underlying molecular mechanisms contributing to SNS regulation of SF-induced inflammatory states are not fully understood. To assess the effects of the SNS system, C57BL/6j female mice were placed in automated SF chambers (12L:12D) and subjected to either …