| Summary: | The aim of this project was to determine the effect that route of infection has on the incubation period and terminal pathology of experimental scrapie. Infection was established either by injection into the peritoneum or the <i>biceps femoralis</i> of the leg, or orally by administration of the agent with food. As a secondary study an experiment was devised to investigate the possible transport of scrapie infectivity in the central nervous system (CNS) of mice lacking a functional <i>prn-p</i> gene. The primary study was carried out using a combination of immunohistochemistry, histopathology and computerised image analysis. The study of agent transport was done by bioassay for reasons of sensitivity. C57B1 mice were infected with ME7 scrapie by the routes described above and groups of animals were serially sacrificed at between 5 and 7 timepoints during the course of the disease. The timepoints were chosen so that tissues representative of early, mid and late/terminal infection could be collected for study. Specific antibodies were used to detect the presence of PrP and GFAP whilst vacuolation was detected by standard haematoxylin and eosin staining. In the experiment to study the transport of infectivity in mice devoid of endogenous PrP the results suggest that some limited transport is possible. This is the result of a study using the projection of the optic nerve as a controlled system for assessing the transport of infectivity along defined neuroanatomical pathways. In conclusion, the results of the work described in this thesis show that oral infection, at least in experimental systems, is a highly efficient route of infection that results in significantly more severe pathology than either the intramuscular or intraperitoneal routes. The efficiency of oral infection may have implications for human disease with reference to new variant CJD (nvCJD).
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