The mouse is a popular and versatile model for the study of scrapie and other transmissible spongiform encephalopathies. In this chapter, information is given for preparation of infectious material for inoculation and a method of clinical scoring that yields accurate and reproducible quantification of the scrapie incubation period. With the help of histopathological and immunopathological techniques, we can detect brain pathological changes in scrapie-infected animals at the cellular and molecular level. We will also describe the histological and immunocytochemistry methods we use for scrapie research, outline step-by-step procedures, discuss tissue preparation, fixation, and processing of specimens, and provide special hints to achieve successful staining. We also include our results of PrPSc and GFAP immunostaining in scrapie research. In conclusion, immunopathological staining is an important and useful tool in the research of scrapie pathology.
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