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Articles 1 - 12 of 12
Full-Text Articles in Life Sciences
Examining The Role Of Chloride Homeostasis And Pge2 Signaling In The Neuroendocrine Stress Response To Inflammation, Samuel A. Mestern
Examining The Role Of Chloride Homeostasis And Pge2 Signaling In The Neuroendocrine Stress Response To Inflammation, Samuel A. Mestern
Electronic Thesis and Dissertation Repository
The brain senses inflammatory signals and drives the release of glucocorticoids (GCs) — potent immunosuppressants — via the activation of the hypothalamic-pituitary-adrenal (HPA) axis. This inflammation-induced HPA axis activation is largely mediated by prostaglandin E2 (PGE2), acting on two subtypes of the PGE2 receptor, EP1 and EP3. Recently, our group revealed EP3 signaling mechanisms that excite HPA axis regulatory neurons. This thesis sought to tease out the remaining EP1 signaling mechanisms. Considering that the excitability of HPA axis regulatory neurons is constrained by GABAA receptor-mediated synaptic inhibition that relies on low-level intracellular Cl-. We hypothesized that PGE2-EP1 …
Meningeal B Cells In Central Nervous System Autoimmunity: Their Phenotype And Susceptibility To Therapeutic Depletion, Yodit Tesfagiorgis
Meningeal B Cells In Central Nervous System Autoimmunity: Their Phenotype And Susceptibility To Therapeutic Depletion, Yodit Tesfagiorgis
Electronic Thesis and Dissertation Repository
B cell depleting therapies have been effective in the treatment of Multiple Sclerosis (MS), yet to date little is known about how B cells promote disease pathogenesis. B cells can be found invading the meninges around the brain and spinal cord in MS, where they cluster in association with T cells. These meningeal B cells clusters are often adjacent to demyelinating lesions suggesting this may be a site where B cells are exerting their pathogenic effects. The purpose of this thesis was to understand the contribution of meningeal B cells to central nervous system (CNS) autoimmunity, by characterizing their phenotype …
Hpv Mediated Antagonism Of The Il-18 Proinflammatory Pathway In Head And Neck Cancer, Wyatt W. Anderson
Hpv Mediated Antagonism Of The Il-18 Proinflammatory Pathway In Head And Neck Cancer, Wyatt W. Anderson
Electronic Thesis and Dissertation Repository
In this thesis, I examined the effect of human papillomavirus (HPV) on the proinflammatory IL-18 cytokine pathway in head and neck cancers. I investigated the expression and methylation of genes associated with this pathway using The Cancer Genome Atlas (TCGA) data. In HPV+ cancers, IL18, CASP1, and AIM2 were downregulated, while IL18BP was upregulated compared to HPV- cancers and adjacent non-cancerous tissues, and IL18’s promoter was significantly more methylated. I compared HPV+ and HPV- head and neck cancer cell lines for expression of RNA and protein levels of IL-18 and IL-18BP by qPCR, western blot, and ELISA. IL-18 …
Monocyte Mri Relaxation Rates Are Regulated By Extracellular Iron And Hepcidin, Praveen S.B Dassanayake
Monocyte Mri Relaxation Rates Are Regulated By Extracellular Iron And Hepcidin, Praveen S.B Dassanayake
Electronic Thesis and Dissertation Repository
Monocytes are an important immune cell type in chronic inflammatory conditions like atherosclerosis and heart failure. The increase in number of monocytes released to the peripheral blood circulation, the differentiation of monocytes to macrophages, and the presence of different macrophage subpopulations during pro- and anti-inflammatory stages of tissue injury may provide markers for monitoring inflammation. In particular, changes in monocyte iron metabolism during an inflammatory response may increase the possibility of tracking these immune cells non-invasively using magnetic resonance imaging (MRI). When secretion of the polypeptide hormone hepcidin is stimulated during inflammation, it binds the iron export protein ferroportin (FPN) …
Brain-Specific And Systemic Inflammatory Response Following Repetitive Concussive Impact In A Mouse Model, So Young Eo
Brain-Specific And Systemic Inflammatory Response Following Repetitive Concussive Impact In A Mouse Model, So Young Eo
Electronic Thesis and Dissertation Repository
Concussion is the most common form of mild traumatic brain injury (mTBI). TBI resolution is modulated by neuroinflammation, which is augmented by the infiltration of innate immune cells from the circulation. Peripheral, myeloid immune cells not only invade neural tissues but other organs as well causing local inflammation and tissue damage, known as systemic inflammatory response syndrome. Here, I assessed the temporal and anatomical nature of the neural and systemic cellular inflammatory response to repetitive, mTBI in a 3-hit mouse model of concussion. The results showed significant microglial activity, accumulation of peripheral myeloid cells and prominent axonal damage post-injury. The …
White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit
White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit
Electronic Thesis and Dissertation Repository
White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …
Role Of High Molecular Weight Hyaluronan In Ultraviolet B Light-Induced Transformation, Katelyn Cousteils
Role Of High Molecular Weight Hyaluronan In Ultraviolet B Light-Induced Transformation, Katelyn Cousteils
Electronic Thesis and Dissertation Repository
Keratinocyte carcinomas (KCs) are the most common cancers globally. Ultraviolet light is the key risk factor for these cancers but sunscreen has proven ineffective in their prevention, indicating a need for new prophylactic agents. Chronic elevation of high molecular weight (HMW) tissue hyaluronan (HA) in skin is linked to tumor resistance in the naked mole rat. To directly assess the role of this polysaccharide in resistance to keratinocyte tumors, a HMW HA phosphatidylethanolamine (HA-PE) formulation that penetrates skin and accumulates as coats around keratinocytes was prepared. The tumor resistance properties of the HA-PE formulation were tested in a mouse model …
Evaluating Evolving Leukocyte Populations In Peripheral Blood Circulation Post-Concussion In A Human Longitudinal Analysis Of Female Athletes, Kevin A. Blackney
Evaluating Evolving Leukocyte Populations In Peripheral Blood Circulation Post-Concussion In A Human Longitudinal Analysis Of Female Athletes, Kevin A. Blackney
Electronic Thesis and Dissertation Repository
Concussions are generating increasing concern due to potential long-term neurological consequences. Currently there is no universally recognized diagnostic approach for concussion. I hypothesize that a signature temporal response of biomarkers of inflammation in systemic circulation will provide an objective diagnosis of concussion and could also be used to track patient recovery. The Western University women’s rugby team underwent blood draws at pre-season and post-season as a baseline evaluation, and players determined to have sustained a concussion underwent repeat blood analysis post-concussion. Blood samples were analyzed by flow cytometry to profile immune cell populations alongside accepted concussion assessments, and complete blood …
The Role Of Sirtuin 6 In Maintaining Vascular Integrity, Sharon Z. Leung
The Role Of Sirtuin 6 In Maintaining Vascular Integrity, Sharon Z. Leung
Electronic Thesis and Dissertation Repository
Oxidative stress is an underlying cause for vascular pathologies including inflammation, hypertension, and atherosclerosis. Sirtuins (SIRTs) are a family of NAD+ dependent deacetylases with pronounced roles in cellular metabolism and aging. SIRT6 is expressed in vascular smooth muscle cells (SMCs) and may offer protection from oxidative stress-induced damage. To study the role of SIRT6 in SMCs, we created a novel strain of SMC-specific SIRT6-deficient (SIRT6KO) mice with Cre-lox technology. Because no defects were observed in the aortas of SIRT6KO mice, they were then infused with angiotensin II (Ang II) to induce oxidative stress. Compared with vehicle controls, SIRT6KO mice developed …
The Role Of Streptococcus Salivarius As A Modulator Of Homeostasis In The Oral Cavity, Kyle W. Macdonald
The Role Of Streptococcus Salivarius As A Modulator Of Homeostasis In The Oral Cavity, Kyle W. Macdonald
Electronic Thesis and Dissertation Repository
The oral cavity contains many different surfaces all colonized by prokaryotes, of which over 700 have been identified. While almost all people have some degree of plaque formation, the more concerning diseases of caries, candidiasis and periodontal disease afflict many patients and represent a major public health concern. As these are all diseases which have a component attributable to parts of the microbiota, efforts to manipulate the microbes has until recently involved use of antimicrobial agents. However, due to side effects, resistance and failure to restore homeostasis, this approach is limited. As an alternative, the administration of beneficial microbes (probiotics) …
Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic
Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic
Electronic Thesis and Dissertation Repository
The peroxisome proliferator-activated receptor (PPAR) δ is a ligand-dependent transcription factor that has been implicated in metabolic and inflammatory regulation. The molecular and physiological mechanisms by which PPARδ activation regulates lipid metabolism, inflammatory signaling and protection from atherosclerosis in states of metabolic disturbance such as insulin resistance and dyslipidemia, were investigated in a series of in vitro and in vivo studies. In vitro experiments demonstrated that PPARδ activation inhibits atherogenic lipoprotein-induced lipid accumulation and the associated proinflammatory responses. The primary mechanisms for these effects were increased fatty acid β-oxidation, decreased lipoprotein lipase (LPL) activity, reduced MAPK signaling and improved insulin …
Cerebellar Degeneration In Harlequin Mice Is Associated With Inflammation Unaltered By Low-Dose Phenobarbital Treatment, Anita Prtenjaca
Cerebellar Degeneration In Harlequin Mice Is Associated With Inflammation Unaltered By Low-Dose Phenobarbital Treatment, Anita Prtenjaca
Electronic Thesis and Dissertation Repository
Canadian population demographics are shifting to an increase in aged individuals and an increase in the prevalence of neurodegenerative diseases. The post-mitotic nature of most neurons highlights the need to understand the etiology and early mechanisms in neurodegenerative diseases and design targeted therapies. Currently, the etiologies of neurodegeneration are poorly understood but oxidative stress, mitochondrial dysfunction and inflammation are early mechanisms in Alzheimer’s disease, Parkinson’s disease and Amyotrophic Lateral Sclerosis. An anti-aging strategy that can be adapted for use in neurodegeneration is hormesis, where repeated low-level exposures to stressors are beneficial to the cell. Hormesis has demonstrated efficacy in inhibiting …