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Please use this identifier to cite or link to this item: http://hdl.handle.net/1993/3131

Title: Pre-clinical changes during scrapie disease progression in hamsters, detected by Magnetic Resonance Imaging.
Authors: Baydack, Richard Stephen
Supervisor: Booth, Timothy (Medical Microbiology)
Examining Committee: Coombs, Kevin (Medical Microbiology) Glavin, Gary (Pharmacology and Therapeutics) Westaway, David (University of Alberta)
Graduation Date: February 2009
Keywords: prion
scrapie
MRI
diagnosis
Issue Date: 12-Feb-2009
Abstract: Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of invariably fatal neurodegenerative diseases of both humans and animals, thought to be caused by the abnormally folded prion protein PrPSc. Prion disease research continues to be faced by a number of difficult challenges. First, the unequivocal diagnosis of most prion diseases currently requires the post-mortem collection of central nervous system tissue, either for histological examination or Western blot analysis; second, a viable treatment for clinical stage disease has not yet been identified; third, the exact details of disease pathogenesis have not been elucidated; and fourth, the normal function of PrPC is not definitively known. The primary objective of the studies presented here was to diagnose prion disease in live animals, using Magnetic Resonance Imaging (MRI). Increases in T2 relaxation time and apparent diffusion coefficient (ADC) were observed very early following the infection of Syrian golden hamsters with the 263K strain of scrapie. These changes were evident well before the appearance of either clinical symptoms or the typical histological changes characteristic of prion disease, suggesting that they are the result of the progressive accumulation of fluid, and that this may constitute a novel early marker of prion disease pathogenesis. Following the establishment of this model system, a secondary objective was composed: to test the viability of a potential treatment (pentosan polysulphate) using a number of different treatment regimens. It was determined that pentosan polysulphate (PPS) was ineffective as a treatment unless it was administered intra-cerebrally very early in infection, although it was shown to slow the appearance of the histological hallmarks of prion disease. In response to the results of these studies, a potential model was proposed, relating PrP, aquaporin-4 (AQP4) regulation, and oedema. Although speculative, this model may have implications for both normal PrPC function and disease pathogenesis.
URI: http://hdl.handle.net/1993/3131
Appears in Collection(s):FGS - Electronic Theses & Dissertations (Public)

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RBaydack PhD Thesis.pdfThesis file22.91 MBAdobe PDFView/Open
Control Cortex GFAP.tifAppendix 5 Image file 19.45 MBTIFFView/Open
Control Cortex H and E.tifAppendix 5 Image file 29.45 MBTIFFView/Open
Control Cortex PrP.tifAppendix 5 Image file 39.45 MBTIFFView/Open
Control Hippocampus GFAP.tifAppendix 5 Image file 49.45 MBTIFFView/Open
Control Hippocampus H and E.tifAppendix 5 Image file 59.45 MBTIFFView/Open
Control Hippocampus PrP.tifAppendix 5 Image file 69.45 MBTIFFView/Open
Control Hypothalamus GFAP.tifAppendix 5 Image file 79.45 MBTIFFView/Open
Control Hypothalamus H and E.tifAppendix 5 Image file 89.45 MBTIFFView/Open
Control Hypothalamus PrP.tifAppendix 5 Image file 99.45 MBTIFFView/Open
Control Thalamus GFAP.tifAppendix 5 Image file 109.45 MBTIFFView/Open
Control Thalamus H and E.tifAppendix 5 Image file 119.45 MBTIFFView/Open
Control Thalamus PrP.tifAppendix 5 Image file 129.45 MBTIFFView/Open
Scrapie Cortex GFAP.tifAppendix 5 Image file 139.45 MBTIFFView/Open
Scrapie Cortex H and E.tifAppendix 5 Image file 149.45 MBTIFFView/Open
Scrapie Cortex PrP.tifAppendix 5 Image file 159.45 MBTIFFView/Open
Scrapie Hippocampus GFAP.tifAppendix 5 Image file 169.45 MBTIFFView/Open
Scrapie Hippocampus H and E.tifAppendix 5 Image file 179.45 MBTIFFView/Open
Scrapie Hippocampus PrP.tifAppendix 5 Image file 189.45 MBTIFFView/Open
Scrapie Hypothalamus GFAP.tifAppendix 5 Image file 199.45 MBTIFFView/Open
Scrapie Hypothalamus H and E.tifAppendix 5 Image file 209.45 MBTIFFView/Open
Scrapie Hypothalamus PrP.tifAppendix 5 Image file 219.45 MBTIFFView/Open
Scrapie Thalamus GFAP.tifAppendix 5 Image file 229.45 MBTIFFView/Open
Scrapie Thalamus H and E.tifAppendix 5 Image file 239.45 MBTIFFView/Open
Scrapie Thalamus PrP.tifAppendix 5 Image file 249.45 MBTIFFView/Open
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