[Show abstract][Hide abstract] ABSTRACT: An experimental oral bovine spongiform encephalopathy (BSE) challenge study was performed to elucidate the route of infectious prions from the gut to the central nervous system in preclinical and clinical infected animals. Tissue samples collected from the gut and the central and autonomic nervous system from animals sacrificed between 16 and 44 months post infection (mpi) were examined for the presence of the pathological prion protein (PrP(Sc)) by IHC. Moreover, parts of these samples were also bioassayed using bovine cellular prion protein (PrP(C)) overexpressing transgenic mice (Tgbov XV) that lack the species barrier for bovine prions. A distinct accumulation of PrP(Sc) was observed in the distal ileum, confined to follicles and/or the enteric nervous system, in almost all animals. BSE prions were found in the sympathetic nervous system starting at 16 mpi, and in the parasympathetic nervous system from 20 mpi. A clear dissociation between prion infectivity and detectable PrP(Sc) deposition became obvious. The earliest presence of infectivity in the brain stem was detected at 24 mpi, whereas PrP(Sc) accumulation was first detected after 28 mpi. In summary, our results decipher the centripetal spread of BSE prions along the autonomic nervous system to the central nervous system, starting already halfway in the incubation time.
Preview · Article · Jun 2012 · American Journal Of Pathology
[Show abstract][Hide abstract] ABSTRACT: It is known from earlier studies that the pathogenesis of BSE in cattle differs considerably from the TSE pathogenesis in sheep, where the lymphoreticular system (LRS) is majorly involved in the transport and propagation of the agent. In cattle, the BSE agent has only been detected in the Peyer's patches of the distal ileum and in the tonsils, which have both been identified as the portal of entry for the agent after oral uptake. It was shown that as opposed to most other animal species, in cattle the BSE agent amplifies almost exclusively in the central and peripheral nervous system. However, there is growing evidence for a centrifugal spread from the central nervous system into the periphery at the late stage of the disease. Moreover, there are only very limited data available concerning the pathogenesis of both atypical BSE forms, H type and L type BSE, as compared to classical BSE. In this manuscript we summarize the most recent data that we generated on the classical BSE pathogenesis after an oral challenge study that was performed with 56 cattle. Preliminary results on the pathogenesis of both atypical BSE forms are also presented, based on an intracranial challenge of cattle with German isolates of both atypical BSE forms.
No preview · Article · May 2011 · Preventive Veterinary Medicine
[Show abstract][Hide abstract] ABSTRACT: For almost two decades after the discovery of the first bovine spongiform encephalopathy (BSE) case, it was generally accepted that only one BSE strain existed globally. However, in 2004, two novel BSE forms (L-type and H-type) were separately identified in two different European Member States, forms that differed from the classical (C-type) form by their biochemical properties and by the pattern of PrP(Sc) deposition as determined by immunohistochemistry (IHC). 60 atypical BSE cases have been identified worldwide as of November 2010, including one H- and one L-type BSE case each in Germany. However, it was not known whether the biological properties (pathogenesis and agent distribution, as well as transmissibility to other species) of these novel forms were the same as in classical BSE cases. Eleven calves were thus challenged intracranially, five with the German H-type and six with German L-type BSE cases. The experimental design and the clinical studies, followed by laboratory testing, are described in this manuscript.
No preview · Article · Jan 2011 · Journal of Toxicology and Environmental Health Part A