Medicine and Health Sciences Commons^™

Evaluating The Pathological And Behavioural Consequences Of Injecting Amyloid Beta Oligomers In The Rat, Ryan S. Wong

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by progressive neuronal loss and cognitive decline. Currently, no therapeutic treatments are available and our understanding of the disease progression is still unclear. Amyloid beta oligomers (AβO) are potent neurotoxic proteins and may be a potential initiator of the progression of AD. The purpose of this project was to identify the spatial and temporal consequences of injecting AβO into the rat brain by evaluating pathological and behavioural outcomes. We hypothesized that injecting AβO into the rat brain will result in microglial response as well as behavioural and …

Deep Brain Stimulation And Its Effects On Parkinson Disease Spatiotemporal Gait Parameters., Greydon Gilmore

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) alleviates common appendicular PD symptoms, such as: tremor, rigidity and bradykinesia. However, the effect STN-DBS has on modulating axial gait features has not been properly quantified objectively. The purpose of the present thesis was to investigate the role STN-DBS plays in modulating specific gait features such as pace, asymmetry, variability, rhythm and postural control. It is hypothesized that axial gait function is regulated predominantly by non-dopaminergic control systems. In the acute immediate post-operative phase a surgical effect, named the microlesion effect (MLE), is thought to produce a transient improvement of appendicular and axial symptoms. …

Role Of Cerebrovascular Abnormality In Neurodegenerative Disease And Subcortical Ischemic Disease: Ct Perfusion And Pet Imaging, Jun Yang

Electronic Thesis and Dissertation Repository

Clinical studies indicate that about 30% ~ 50% of patients have cognitive impairment after the first or recurrent stroke. Ischemic injury, particularly subcortical lesions, caused by stroke has been demonstrated to further exacerbate cognitive impairment of Alzheimer’s disease (AD) and vascular dementia. However, the mechanisms whereby cerebrovascular abnormalities contribute to neurodegeneration at early stage of disease and eventually to cognitive decline remain unclear. CT perfusion and positron emission tomography (PET) were used to investigate early mechanisms in a rat comorbid model of cerebral ischemia (CI) and β-amyloid (Aβ, a pathological hallmark of AD) toxicity, and in patients with small subcortical …

Quantifying The Effects Of Systematic Stn-Dbs Programming On Rest And Postural Tremor In Idiopathic Parkinson Disease Patients, Kristina Ognjanovic

Electronic Thesis and Dissertation Repository

Parkinson’s disease (PD) is a complex neurodegenerative disorder that encompasses both motor and non-motor symptoms. These symptoms and their severity are typically assessed by scale based measures in a clinical setting. Scale- based assessments of PD patients undergoing bilateral subthalamic nucleus deep brain stimulation surgery (STN-DBS) such as the Unified Parkinson Disease Rating Scale (UPDRS) are commonly used in a clinical setting to assess symptom severity and progression. However, the subjective nature of these and other clinical scales call into question both the sensitivity and accuracy of patient assessment over time. An objective quantification of rest and postural tremor of …

Investigating Cortical Changes In Cervical Spondylotic Myelopathy Using Functional Magnetic Resonance Imaging, Proton Magnetic Resonance Spectroscopy And Diffusion Tensor Imaging, Izabela Kowalczyk

Electronic Thesis and Dissertation Repository

Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction in older adults. CSM can present abruptly with severe symptoms of neurological impairment or insidiously with a slow stepwise deterioration. There is no current imaging modality or biomarker that can help predict which patient will successfully respond to conservative versus surgical treatment. The goal of this thesis was to follow CSM patients longitudinally to assess how brain function, metabolism, and structure correlate to clinical outcomes in the context of recovering neurological function following surgery.

Chapter 1 of this thesis will provide a detailed literature review of the …

Are Patients At The Centre Of Care?: A Qualitative Exploration Of Myotonic Dystrophy Type 1 (Dm1), Kori A. Ladonna

Electronic Thesis and Dissertation Repository

Health care for individuals living with myotonic dystrophy (DM1)—an uncommon, life-limiting neurological condition for which there are few treatments—may be challenged by patients’ symptoms including cognitive and behavioral impairments. Is patient-centered care—which incorporates the values, experiences and expertise of patients and their caregivers—feasible or achievable? Uncovering patients’ and their caregivers’ experiences of living with DM1, their health care expectations, and their health care providers’ (HCP) perspectives about care is essential for examining patient-centered care in this population. Therefore, the purpose of this research is to: (1) add patients’ and caregivers’ voices to the literature, (2) explore on-going care provision for …

Impacts Of Diabetic Neuropathy On The Human Neuromuscular System, Matti D. Allen

Electronic Thesis and Dissertation Repository

Diabetes mellitus (DM) imparts vascular and metabolic stressors that cause damage and dysfunction to the human nervous system. The disorder associated with this dysfunction is termed diabetic polyneuropathy (DPN). Although DPN has been associated with muscle weakness and atrophy, the extent of its impacts on the neuromuscular system is not well understood. The five studies presented in my thesis investigated how DPN affects the neuromuscular system in humans, from the motor neuron to skeletal muscle contractile properties, using a combination of electromyography (EMG), dynamometry and magnetic resonance imaging (MRI) techniques.

The purpose of Studies 1 and 2 was to determine …

Managing Uncertainty In Young-Onset Parkinson's Disease, Michael J. Ravenek

Electronic Thesis and Dissertation Repository

Typically considered a disease of old-age, Parkinson’s disease can affect those younger in life, i.e., before the age of 55, when it is referred to as young-onset Parkinson’s disease (YOPD). Using constructionist grounded theory, this research sought to understand how, and why, individuals with YOPD became informed about their disease over time. A total of 39 individuals, who self-identified as living with YOPD, took part in this study which was organized according to four cycles of data collection. These cycles utilized focus groups, in-depth interviews and a private online discussion board, supplemented by 14 autobiographies written by individuals living with …

Nerve Blood Flow Control In Health & Disease:The Effects Of Type 1 Diabetes And Exercise Training, Terry D. Olver

Electronic Thesis and Dissertation Repository

Peripheral nerve blood flow (NBF) is critical to nerve health. Impaired NBF control may contribute to the progression of diabetes peripheral neuropathy. The purposes of this dissertation were: i) to investigate the acute and chronic effects of hyperglycemia on basal sciatic NBF (measured via Doppler ultrasound), ii) to examine the potential vasodilatory effects of insulin (euglycemic hyperinsulinemic clamp; 10 mµ•kg^-1•min^-1) on NBF control in healthy rats and rats with insulin-treated type 1 diabetes (DS) and iii) to determine if exercise training (~75% VO₂max, 60 min/day, 5 days/wk for 10 wk) improves vasa nervorum reactivity …

Exploring The Structure And Biochemistry Of Oxidation-Mediated Inhibitation Of The Peptidyl-Prolyl Isomerase Pin1, Brendan T. Innes

Electronic Thesis and Dissertation Repository

Pin1 is a phosphorylation-dependent peptidyl-prolyl isomerase that has been shown to be neuroprotective in aging-related neurodegenerative diseases such as Alzheimer's disease (AD). However, it is not active in AD brain, and a recent proteomic screen of Mild Cognitive Impairment (MCI) brain samples revealed that Pin1 is oxidized in the brains of these pre-AD patients. This suggests that this oxidation may be the cause of the loss of the neuroprotective Pin1 function in AD. The Pin1 active site contains a functionally critical cysteine residue (Cys113) with a low predicted pKa, making it highly susceptible to oxidation. We hypothesize that Pin1 is …

Magnetic Resonance Imaging Of Iron In Early Multiple Sclerosis At 3 Tesla, Matthew P. Quinn

Electronic Thesis and Dissertation Repository

Multiple sclerosis (MS) is the most common neurological disease in young Canadians, yet its etiology remains obscure. Two possibly related findings in MS are brain iron deposition and the presence of small veins in white matter lesions. This thesis concerns the development and application of 3 Tesla magnetic resonance imaging tools to image iron and veins in early multiple sclerosis.

To facilitate measurements of iron concentration as well as production of cerebral venograms, we first optimized multi-echo susceptibility weighted imaging (SWI), using numerical simulations and input from physicians. We validated measurements of R2*, an MRI parameter that scales linearly with …

Exploring The Iranian-Canadian Family Experience Of Dementia Caregiving: A Phenomenological Study, Sevil Deljavan

Electronic Thesis and Dissertation Repository

Presently in Canada, there are approximately 500,000 individuals living with dementia, which is expected to increase to over one million by 2038. With Canada’s minority elderly population growing, the number of Iranian-Canadian older adults living with dementia is expected to rise as well. Family caregivers are a significant source of help among Iranian-Canadians and the provision of informal care by adult children for parents with dementia in the Iranian culture is an expression of love and dedication.

This study explored the meaning of the experience of Iranian adult children in Canada caring for a parent with Alzheimer’s disease, the values …

Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is characterized by deposition of the amyloid beta (Ab) peptide in the brain, an event which frequently but not universally correlates with nerve cell death. Although most nerve cells die in response to Ab, small populations of cells are able to survive by becoming resistant to Ab toxicity. Understanding the mechanisms by which cells become resistant to Ab may reveal novel treatments for AD. Interestingly, nerve cell lines selected for resistance against Ab exhibit increased glucose uptake and glycolytic flux. Here I show that these metabolic changes are mediated through an upregulation of pyruvate dehydrogenase kinase 1 …

Characterizing Stomatin-Like Protein 2 And Its Role In Neuron Survival, Lisa A. Foris

Electronic Thesis and Dissertation Repository

Stomatin-like Protein 2 (SLP-2) has been identified as a stress-inducible transcript and has been shown to interact with and stabilize mitochondrial proteins. Since mitochondria are critical for neuronal function, we hypothesized that SLP-2 regulates neuron survival in response to stressful stimuli. A conditional SLP-2 knockout mouse (deletion) and the SN56 cell line (upregulation) were employed to study the role of SLP-2 in mitochondrial dynamics and neuron survival. SLP-2 deficient primary cortical neurons displayed significantly decreased levels of various mitochondrial respiratory chain proteins, indicating SLP-2 contributes to maintenance of mitochondrial membrane integrity. SLP-2 was up-regulated in response to oxidative stress and …

An Investigation Into The Combined Effects Of Β-Amyloid Toxicity And Cerebral Ischemia On The Pathological Expression Of Gangliosides., Jeffrey D. Hepburn

Electronic Thesis and Dissertation Repository

Identifying mechanisms underlying the synergistic pathological interaction between stroke and Alzheimer’s disease (AD) can effectively guide future therapeutic strategies for these highly co-morbid conditions. Aberrant ganglioside expression marked by the pathological accumulation of ganglioside GM3 is common to stroke and AD, yet it is unclear whether GM3 is synergistically enhanced in a comorbid model, or if GM3 is a viable therapeutic target. Adult male Wistar rats received a unilateral ischemic striatal infarct via endothelin-1 (ET-1) injection alone or in combination with bilateral intracerebroventricular injection of the β-Amyloid 25-35 peptide (Aβ) to induce generalized Aβ toxicity (Aβ/ET-1). Animals were sacrificed after …