Thesis (M. Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 111-122).

Alzheimer’s disease and vascular dementia are the leading causes of cognitive disorders in the elderly worldwide. Increasing cases with overlaps in neuropathology between both disorders are becoming evident, giving rise to the concept of “mixed dementia”, which is characterized by cerebrovascular dysregulations along with tauopathies and β-amyloid (Aβ)-associated neurotoxicity. While the exact mechanisms leading to the exhibited vascular-neurodegenerative pathophysiology are still unclear, it is often found that ischemic-stroke contributes to amyloid pathogenesis, thus exacerbating cognitive impairment. Astrocytes, the most abundant cell type in the brain, appear to be important mediators in the central nervous system homeostasis and pathophysiology. This study proposes that upon ischemic stress, endothelin-1 (ET-1) overexpression in astrocytes leads to β-site APP cleaving enzyme 1 (BACE1) upregulation, hence contributing to enhanced amyloid pathology. ET-1 is a potent vasoconstrictor associated to Aβ pathogenesis in the brain, and BACE1 is the rate-limiting enzyme for Aβ synthesis. In order to assess astrocytic responses to ischemic stress, two previously modified astrocytic cell lines, mock-transfected control astrocytes (WT) and ET-1 overexpressing astrocytes (C6), were used. The exposures of WT and C6 cells to oxygen and glucose deprivation (OGD) – to mimic ischemic stress in vitro – evoked no abrupt differences between both cell lines. After OGD, astrocytes were characterized by cellular swelling, detachment from neighboring cells, increased cell death, decreased cell proliferation, and reduced BACE1 expressions during reperfusion. In addition, the attempt to modulate BACE1 protein levels, by blocking the receptor for advanced glycation end products, induced no significant differences. This study also investigated astrocytic ET-1 influences in the neuropathology of the transgenic mouse models APPGET-1 (amyloid precursor protein and astrocytic ET-1 overexpression) and GET-1 through a proteomics approach. The abnormal expressions of tropomyosin-3, transgelin-3, ATP synthase α chain, 3-hydroxyisobutyrate dehydrogenase, superoxide dismutase 1, glutathione S-transferase P1, and peroxiredoxin-6 in the mice hippocampi were identified. It is most likely that these proteins participate in cytoskeleton structural changes, energy metabolism impairment, and oxidant-antioxidant system imbalances that contribute to the observed increased brain atrophy displayed in these two animal models. In summary, this study has identified the possible participation of several proteins in the accelerated declination of cognitive functions exhibited by GET-1 and APPGET-1 mice through a proteomics approach. However, our in vitro results suggest that ET-1 did not play any pivotal role in C6 response to the hypoxic conditions evaluated. Furthermore, results showed no correlation between astrocytic ET-1 and BACE1. Further investigations examining alternative BACE1-independent pathways are required to elucidate the intricate relationship between ET-1 and Aβ in astrocytes. / published_or_final_version / Psychiatry / Master / Master of Philosophy

Introduction: Cognitive impairments occur frequently in stoke survivors, yet current conventional post-stroke care focuses mainly on motor function. Transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are noninvasive brain stimulation techniques (NIBS) that are used in neurological rehabilitation. Its efficacy is well-established in motor recovery post-stroke, but research on its effects on the associated cognitive decline after stroke is fairly new. The aim of this review is to evaluate recent studies and provide a summary on the effects of NIBS on post-stroke cognitive decline. Methods: PubMed and CINAHL were searched using the keywords: “cerebrovascular accident”, “stroke”, “NIBS” or “noninvasive brain stimulation”, “tDCS” or “transcranial direct current stimulation”, and “TMS” or “transcranial magnetic stimulation”. PEDro system was used to assess the quality of the studies that passed the inclusion and exclusion criteria. Results: The initial search returned 1081 citations, among which 12 were included in this review. The mean PEDro score of the studies was 7.5 out of 10. The trials had a total of 176 participants with stroke. Lesion site was heterogeneous. Six trials investigated tDCS, and the other 6 investigated rTMS. The main outcome measures were grouped into 3 domains: memory, visuospatial, and attention. Both tDCS and rTMS resulted in significant changes in the visuospatial domain in terms of improving spatial neglect. The results on memory and attention are mixed, but tDCS shows more consistent results. Conclusion: NIBS is a safe and low-cost treatment that can improve cognitive decline post-stroke. However, the evidence is still lacking due to the small number of trials and sample sizes. More studies need to be conducted in order to establish a proper guideline for usage. Long term effects also need to be investigated. / published_or_final_version / Public Health / Master / Master of Public Health

published_or_final_version / abstract / toc / Psychiatry / Master / Master of Philosophy

Thesis (Ph.D.)--University of Texas at Dallas, 2008. / Includes vita. Includes bibliographical references (leaves 85-91)

Thesis (Ph. D.)--Drexel University, 2004. / Includes abstract and vita. Includes bibliographical references (leaves 110-124).

Thesis (Ph.D.)--Ohio University, November, 2004. / Includes bibliographical references (p. 89-101)

Thesis (Psy. D.)--University of Hong Kong, 2008. / Includes bibliographical references (p. 99-129).

Thesis (M. Phil.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Thesis (M.A.)--York University, 2008. Graduate Programme in Psychology. / Typescript. Includes bibliographical references (leaves 78-84). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR51523