Immunohistochemical approach to the pathogenesis of bovine spongiform encephalopathy in its early stages

An immunohistochemical and histochemical study was carried out on the brains of nine cases of BSE-diagnosed cattle as part of the surveillance plan in Catalonia, Spain. The animals had no clinical symptoms reported and were thus at early stages of the disease. The first part of the study consisted of a characterization of PrP(BSE) deposits throughout the encephalon. The behaviour of the different immuno-labelling patterns was analysed and tropism of some patterns towards certain brain areas was described. This tropism is principally directed to the brain stem region; however, an association of the stellate pattern was found with areas where PrP(BSE) is deposited less abundantly, such as the cerebral cortex. Secondly, distinct pathogenesis mechanisms that take place in the early stages of BSE, which would include these cases were investigated. This study describes the glial response to the presence of PrP(BSE) (using antibodies against astrocytic glial fibrillary acidic protein and lectin from Griffonia simplicifolia to identify microglia), the presence of mild oxidative stress phenomena (antibodies against metallothioneins I and II and against nitrated aminoacidic residues: nitrotyrosine), the apparent absence of apoptotic cellular death (cleaved caspase 3) and the preservation of synaptic proteins synaptophysin and small synaptosome-associated 25 kDa protein immuno-labelling. Finally, no alteration of the extra-cellular matrix was detected with the use of Wisteria floribunda agglutinin, a marker for perineuronal nets.