Medicine and Health Sciences Commons^™

Assessing Inflammation In The Pathology Of Knee Osteoarthritis, Zachary J. Koudys

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a joint disease that causes pain, stiffness, and loss of function. Inflammation of the synovium plays a role in the pathology of OA. Macrophages are the dominant immune cells in synovial tissue. Activated macrophages over-express the translocator protein (TSPO). [¹⁸F]FEPPA is a 2^nd generation positron emission tomography (PET) tracer that can target TSPO with high specificity. Hybrid [¹⁸F]FEPPA PET/MRI may enable accurate quantification of macrophage activity in vivo. In this work, [¹⁸F]FEPPA tracer uptake in knee synovial tissue was measured ex vivo using autoradiography and was validated to correlate to …

Measuring Inflammation In The Entire Myocardium In A Canine Model Of Myocardial Infarction With Hybrid Pet/Mri, Benjamin Wilk

Electronic Thesis and Dissertation Repository

Background: After myocardial infarction (MI), fibrosis and an ongoing dysregulated inflammatory response are associated with adverse cardiac remodeling. Fluorodeoxyglucose (FDG) positron emission tomography (PET) is sensitive to inflammation provided suppression protocols are implemented to restrict the uptake of glucose in myocytes. Magnetic resonance imaging can be used to determine extracellular volume, a surrogate measure of fibrosis. In some cases, patients present with markedly reduced flow in the setting of a large infarct, i.e. microvascular obstruction, restricting the delivery of FDG and contrast agents. To overcome this problem, a constant infusion was explored as an alternative to the clinical standard bolus …

Modulation Of Inflammation Driven Wound Healing After Glaucoma Surgery, James J. Armstrong

Electronic Thesis and Dissertation Repository

Dysregulated wound healing contributes to most currently unanswered ophthalmological morbidity. Opacification and structure altering contractures compromise the delicate ocular anatomy upon which ocular function and healthy vision are reliant. Glaucoma filtration surgery, corneal stromal injury, proliferative vitreoretinopathy and age-related macular degeneration are major contributors to ocular morbidity – all with myofibroblast transdifferentiation and pathognomonic scarring activity at their core.

This thesis aims to revaluate the means by which dysregulated ocular wound healing is combated with evidence describing a novel strategy to mitigate its effects. A translational approach was used. An initial retrospective analysis of over ten thousand glaucoma surgeries found …

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 …

Effect Of Carbon Monoxide-Releasing Molecule-3 On The Severity Of Endothelial Dysfunction Due To Elevation Of Hydrostatic Pressure In An In Vitro Model Of Compartment Syndrome, Michel A. Taylor

Electronic Thesis and Dissertation Repository

Compartment syndrome (CS) is a surgical emergency caused by elevated pressure within a closed osseofascial compartment. It leads to microvascular dysfunction, limiting oxygen and nutrient delivery, gas exchange, resulting in cellular anoxia, muscle necrosis and cell death.

Currently, the only effective treatment is surgical fasciotomy. Recently, carbon monoxide (CO) delivered via carbon monoxide releasing molecule-3 (CORM-3) has been shown to improve microvascular perfusion and convey anti-inflammatory benefits in animal models of CS.

The contribution of elevated hydrostatic pressure (EHP) to the pathophysiology of CS was examined in an in vitro model of CS. We found that EHP led to increased …

Therapeutic Application Of Carbon Monoxide In Acute Limb Compartment Syndrome, Aurelia Bihari

Electronic Thesis and Dissertation Repository

Acute limb compartment syndrome (CS), a devastating complication of musculoskeletal trauma, develops in response to elevation of the pressure within a closed osseofascial compartment, producing muscle- and limb-threatening ischemia. Full decompression of all involved compartments by fasciotomy is the current gold-standard therapy, but it must be performed within a surgical window of 6-8 hours, before tissue damage becomes permanent.

Carbon monoxide (CO), a byproduct of heme metabolism, has been shown protective in ischemia. While inhalation of CO leads to elevation of carboxyhemoglobin (COHb), recent development of transitional metal carbonyls, CO-releasing molecules (CO-RMs), particularly the water-soluble CORM-3, delivers CO in a …

Systemic Cyotkines/Chemokines Contribute To Microvascular Dysfunction And Tissue Injury In Compartment Syndrome, Erin S. Donohoe

Electronic Thesis and Dissertation Repository

There are few more devastating complications of musculoskeletal trauma than compartment syndrome (CS). It occurs secondary to elevated pressure within a closed osseofascial compartment, leading to microvascular dysfunction, hypo- perfusion of the tissues, cellular anoxia and ultimately cell death. The aim of this thesis was to prove that CS leads to a systemic inflammatory response, and to examine the specific cytokines/chemokines associated with CS. Twenty-four cytokines/chemokines were measured in a rat model of CS. Additionally, microvascular dysfunction, tissue injury and inflammatory response following the neutralization of pro-inflammatory cytokine, TNF-α, at the time of fasciotomy were assessed using intravital video microscopy …

Potential Therapeutic Role Of Hydrogen Sulfide-Releasing Molecule Gyy4137 In A Rat Model Of Acute Compartment Syndrome., Moustafa Haddara

Electronic Thesis and Dissertation Repository

Acute limb compartment syndrome (ACS) causes a unique form of limb ischaemia, which induces intense inflammatory response resulting in microcirculatory dysfunction, neutrophil activation and cell injury. Increased intracompartmental pressure is the hallmark of ACS. Decompression by fasciotomy is the gold standard treatment. While fasciotomy saves the limb from ischaemic threat, paradoxically, it causes further damage to the muscle by reperfusion injury. In addition, it does not address the inflammatory element purported to increase the tissue injury in ACS.

Recent evidence suggests that hydrogen sulfide (H₂S) can mitigate the damage associated with ischaemia-reperfusion injury. The purpose of this thesis …