Theses and Dissertations
Filtering by
- All Subjects: inflammation
- Creators: School of Life Sciences
- Creators: Hashimoto, Tomoki
In females, critical hormonal shifts occur during puberty, menstruation, pregnancy, and <br/>menopause. The fluctuating ovarian hormone levels across a woman’s lifespan likely contribute <br/>to inflammatory responses driven by the immune system, which is regulated by a variety of <br/>physiological pathways and microbiological cues. Pregnancy in particular results in drastic <br/>changes in circulating hormone profiles, and involves a variety of physiological changes, <br/>including inflammatory responses of the immune system. There is evidence that these effects are <br/>mediated, in part, by the significant hormone fluctuations that characterize pregnancy and <br/>postpartum periods. This thesis highlights and synthesizes important physiological changes <br/>associated with pregnancy, and their potential implications on cognitive and brain aging in <br/>women. A tertiary model of cognition is presented depicting interactions between hormonal <br/>history, reproductive history, and immune functions. This research is important to create a better <br/>understanding of women’s health and enhance medical care for women throughout pregnancy <br/>and across reproductive hormone shifts across the lifespan.
body weight. Microarray analysis identified 53 probe sets significantly altered post- ω-3PUFA, with APOE being one of the most upregulated genes. High dose of long chain ω-3PUFA supplementation modulates significant changes in plasma fatty acid profile, AT and systemic inflammation. These findings associate with significant improvement of insulin-stimulated glucose disposal. Unbiased microarray analysis of Sc fat biopsy identified APOE as the most differentially regulated gene after ω-3PUFA 22 supplementation. We speculate that ω-3PUFA increases macrophage-derived APOE mRNA levels with anti-inflammatory properties.
Spinal cord injury (SCI) is characterized by severe tissue damage and extreme inflammation involving prolonged invasion of inflammatory cells. Following SCI, there is long-term disability and treatment is limited. We previously demonstrated that sustained subdural infusion of the anti-inflammatory protein, Serp-1, significantly improved functional recovery and reduced inflammatory cell invasion following SCI. We hypothesized that sustained delivery of immune-modulating Serp-1 using a chitosan-collagen hydrogel would demonstrate therapeutic benefits and reduce damage following forceps crush-induced SCI. Following the dorsal column crush injury, we observed that for rats treated with high-dose (100 μg/50 μL) Serp-1, functional motor improvement was observed. There was also a more pronounced neuroprotective effect in comparison to the low-dose (10 μg/50 μL) treatment, which was likely attributable to suppression of local inflammation. Conversely, sustained infusion of low-dose Serp-1 CCH did not enhance recovery. Thus, sustained delivery of immune-modulating Serp-1 through a chitosan-collagen hydrogel exhibits neuroprotective potential following acute SCI.
In intracranial aneurysms, multiple factors and biochemical pathways are believed to be involved in the event of a rupture. The epidermal growth factor receptor (EGFR) activation pathway is of particular interest as a way to understand and target the mechanism of rupture due to its established role in cellular proliferation and inflammation. Furthermore, unfolded protein responses in vascular cells’ endoplasmic reticulum (ER), known as ER stress, have emerged as a potential downstream mechanism by which inflammatory EGFR activation may lead to aneurysm rupture. The purpose of this project was to investigate the role of EGFR inhibition on the aneurysm rupture rate in a preclinical model, investigate the role of ER stress induction on the aneurysm rupture rate, and confirm which cellular phenomenon lies upstream in this mechanistic cascade. Based on analyses of aneurysm rupture rate and gene expression in the Circle of Willis, ER stress and inflammatory unfolded protein responses were found to be downstream of initial EGFR activation, which may be an effective therapeutic target for preventing aneurysm rupture in a clinical setting.