Prion Infectivity and PrPBSE in the Peripheral and Central Nervous System of Cattle 8 Months Post Oral BSE Challenge.

After oral exposure of cattle with classical bovine spongiform encephalopathy (C-BSE), the infectious agent ascends from the gut to the central nervous system (CNS) primarily via the autonomic nervous system. However, the timeline of this progression has thus far remained widely undetermined. Previous studies were focused on later time points after oral exposure of animals that were already 4 to 6 months old when challenged. In contrast, in this present study, we have orally inoculated 4 to 6 weeks old unweaned calves with high doses of BSE to identify any possible BSE infectivity and/or PrPBSE in peripheral nervous tissues during the first eight months post-inoculation (mpi). For the detection of BSE infectivity, we used a bovine PrP transgenic mouse bioassay, while PrPBSE depositions were analyzed by immunohistochemistry (IHC) and by protein misfolding cyclic amplification (PMCA). We were able to show that as early as 8 mpi the thoracic spinal cord as well as the parasympathetic nodal ganglion of these animals contained PrPBSE and BSE infectivity. This shows that the centripetal prion spread starts early after challenge at least in this age group, which represents an essential piece of information for the risk assessments for food, feed, and pharmaceutical products produced from young calves.

Detection of PrPBSE and prion infectivity in the ileal Peyer's patch of young calves as early as 2 months after oral challenge with classical bovine spongiform encephalopathy.

In classical bovine spongiform encephalopathy (C-BSE), an orally acquired prion disease of cattle, the ileal Peyer's patch (IPP) represents the main entry port for the BSE agent. In earlier C-BSE pathogenesis studies, cattle at 4-6 months of age were orally challenged, while there are strong indications that the risk of infection is highest in young animals. In the present study, unweaned calves aged 4-6 weeks were orally challenged to determine the earliest time point at which newly formed PrPBSE and BSE infectivity are detectable in the IPP. For this purpose, calves were culled 1 week as well as 2, 4, 6 and 8 months post-infection (mpi) and IPPs were examined for BSE infectivity using a bovine PrP transgenic mouse bioassay, and for PrPBSE by immunohistochemistry (IHC) and protein misfolding cyclic amplification (PMCA) assays. For the first time, BSE prions were detected in the IPP as early as 2 mpi by transgenic mouse bioassay and PMCA and 4 mpi by IHC in the follicular dendritic cells (FDCs) of the IPP follicles. These data indicate that BSE prions propagate in the IPP of unweaned calves within 2 months of oral uptake of the agent.

Osteomorphometry of the bones of the thigh, crus and foot in the New Zealand white rabbit (Oryctolagus cuniculus).

The morphology and morphometry of the bones of the thigh, crus and foot of ten adult New Zealand white rabbits were investigated to outline the peculiarities of the species and attempt to establish a morpho-functional paradigm. The femur, tibia-fibular, tarsus, metatarsals and digits of the right and left limbs were extracted and properly macerated. Gross observations of the femur revealed the presence of three trochanters. The greater trochanter was considerably higher than the head of the femur. The femoral head possessed a fovea capitis. The distal part of the femur had prominent condylus lateralis, condylus medialis, epicondylus lateralis and epicondylus medialis. The femur had an average length of 8.230 cm (SD +/- 0.086). The proximal aspect of the tibia possessed a prominent tuberosity and two condyles. Distal fusion of the tibia and fibula was observed since about half of the total tibia length. The distal articular surface of the tibia was about twice as wide medio-laterally than dorso-ventrally and deeply excavated to accommodate the relief of the talus trochlea. The right and left tibia length measured 9.100 cm (+/- 0.119) and 9.080 cm (+/- 0.120), respectively. Six distinct tarsal bones were observed. The foot was complete with four digits. The relative lengths of the metatarsal bones were III > II > IV > I. Various other parameters were measured. Bilateral asymmetry was observed in all the considered parameters.