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.

A meta-analysis on RT-QuIC for the diagnosis of sporadic CJD.

Creutzfeld-Jakob disease (CJD) is a fatal neurodegenerative disease which belongs to the family of transmissible spongiform encephalopathies (TSEs), or prion diseases. Historically, CJD diagnosis has been based on the combination of clinical features and in vivo markers, including CSF protein assays, MRI and EEG changes. Brain-derived CSF proteins, such as 14-3-3, t-tau and p-tau have been largely used to support the diagnosis of probable CJD, although with certain limitations concerning sensitivity and specificity of these tests. More recently, a new method for the pre-mortem diagnosis of sporadic CJD has been developed, based on the ability of PrPsc to induce the polymerization of protease-sensitive recombinant PrP (PrPsen) into amyloid fibrils, and is known as Real-Time Quaking- Induced Conversion (RT-QuIC) assay allows the detection of > 1 fg of PrPsc in diluted CJD brain homogenate and a variety of biological tissues and fluids. In the present study, we did a meta-analysis on the liability of RT-QuIC method in the diagnosis of sporadic CJD, in comparison to 14-3-3 and Tau protein. Twelve studies were finally included in the statistical analysis which showed that RT-QuIC has a very high specificity and comparable sensitivity to 14-3-3 protein and Tau protein in the CSF, and hence can be used as a reliable biomarker for the diagnosis of sporadic CJD.

Animal prion diseases: the risks to human health.

Transmissible spongiform encephalopathies (TSEs) or prion diseases of animals notably include scrapie in small ruminants, chronic wasting disease (CWD) in cervids and classical bovine spongiform encephalopathy (C-BSE). As the transmission barrier phenomenon naturally limits the propagation of prions from one species to another, and the lack of epidemiological evidence for an association with human prion diseases, the zoonotic potential of these diseases was for a long time considered negligible. However, in 1996, C-BSE was recognized as the cause of a new human prion disease, variant Creutzfeldt-Jakob disease (vCJD), which triggered an unprecedented public health crisis in Europe. Large-scale epidemio-surveillance programs for scrapie and C-BSE that were implemented in the EU after the BSE crisis revealed that the distribution and prevalence of prion diseases in the ruminant population had previously been underestimated. They also led to the recognition of new forms of TSEs (named atypical) in cattle and small ruminants and to the recent identification of CWD in Europe. At this stage, the characterization of the strain diversity and zoonotic abilities associated with animal prion diseases remains largely incomplete. However, transmission experiments in nonhuman primates and transgenic mice expressing human PrP clearly indicate that classical scrapie, and certain forms of atypical BSE (L-BSE) or CWD may have the potential to infect humans. The remaining uncertainties about the origins and relationships between animal prion diseases emphasize the importance of the measures implemented to limit human exposure to these potentially zoonotic agents, and of continued surveillance for both animal and human prion diseases.

Prion-related peripheral neuropathy in sporadic Creutzfeldt-Jakob disease.

OBJECTIVE: To assess whether the involvement of the peripheral nervous system (PNS) belongs to the phenotypic spectrum of sporadic Creutzfeldt-Jakob disease (sCJD). METHODS: We examined medical records of 117 sCJDVV2 (ataxic type), 65 sCJDMV2K (kuru-plaque type) and 121 sCJDMM(V)1 (myoclonic type) subjects for clinical symptoms, objective signs and neurophysiological data. We reviewed two diagnostic nerve biopsies and looked for abnormal prion protein (PrPSc) by western blotting and real-time quaking-induced conversion (RT-QuIC) in postmortem PNS samples from 14 subjects. RESULTS: Seventy-five (41.2%) VV2-MV2K patients, but only 11 (9.1%) MM(V)1, had symptoms or signs suggestive of PNS involvement occurring at onset in 18 cases (17 VV2-MV2K, 9.3%; and 1 MM(V)1, 0.8%) and isolated in 6. Nerve biopsy showed a mixed predominantly axonal and demyelinating neuropathy in two sCJDMV2K. Electromyography showed signs of neuropathy in half of the examined VV2-MV2K patients. Prion RT-QuIC was positive in all CJD PNS samples, whereas western blotting detected PrPSc in the sciatic nerve in one VV2 and one MV2K. CONCLUSIONS: Peripheral neuropathy, likely related to PrPSc deposition, belongs to the phenotypic spectrum of sCJDMV2K and VV2 and may mark the clinical onset. The significantly lower prevalence of PNS involvement in typical sCJDMM(V)1 suggests that the PNS tropism of sCJD prions is strain dependent.

Gross and histopathological pitfalls found in the examination of 3338 cattle brains submitted to the BSE surveillance program in Brazil / Ciladas macroscópicas e histopatológicas encontradas no exame de 3338 encéfalos de bovinos submetidos ao programa de vigilância da EEB no Brasil

This study stems from the findings during the gross and histopathological exam of 3,338 cattle brains as part of the bovine spongiform encephalopathy (BSE) active surveillance program of the Brazilian Ministry of Agriculture, Livestock, and Supply from 2001 to 2005. The work was carried out in the Veterinary Pathology Laboratory of the Federal University of Santa Maria which at the time (2001-2007) was the national reference laboratory for the diagnosis of BSE and other transmissible spongiform encephalopathies. Both gross and histopathological aspects are described. Several gross aspects were annotated: anatomic normal structures not commonly recognized (non-lesions), lesions of no clinical significance, postmortem changes and artifacts; all these can amount to important pitfalls that distract the pathologist during the routine gross examination of the central nervous system (CNS). Accordingly, equivalent pitfalls were described in the histological examination. Non-lesions observed were the pineal body, embryo remnants such as the external germinal layer of the cerebellum, subependymal plates, and clusters of neuroblasts in the basal ganglia; or circumventricular structures such as area postrema, subcomisural organ, and melanosis in the leptomeninges and vessel walls. Lesions with little or no clinical importance included age-related changes as lipofuscin, hemosiderin, mineralization and hyalinization of vessel walls within the brain and meninges. Corpora amylacea and corpora arenacea were detected respectively in astrocyte processes and the pineal body. Cytoplasmic neuronal vacuolization was observed in the red nucleus and habenular nucleus. Sarcocystis sp. without a correspondent inflammatory reaction was rarely observed. Included within findings with no clinical manifestation were axonal spheroids and perivascular mononuclear cuffings. Changes in the CNS due to killing, sampling and fixation methods can obscure or distract from the more critical lesions. The ones related to the process of killing included hemorrhages caused in cattle destroyed by a captive bolt. Artifacts related to sampling and handling of CNS tissue consisted of inclusion of bone sand in the neural tissue from sawing the calvarium; dark neurons produced by excessive handling of the brain, and micro-organisms that contaminated the tissues during sampling or histological processing. Postmortem autolytic or putrefactive changes observed included vacuolar changes in the myelin sheath, clear halos surrounding neurons and oligodendrocytes, clusters of putrefaction bacilli within vessels or dispersed throughout the brain tissue associated or not to clear halos. One interesting, and somewhat frequent, postmortem autolytic change found in the bovine brain was the partial dissolution of the granule cell layer (GCL) of the cerebellum, also referred to as conglutination of the GCL or as the French denomination "état glace". Due to the shortage of comprehensive publications in the subject, this review is intended to address the main pitfalls that can be observed in the brain of cattle hoping to help other pathologists avoiding misinterpret them.(AU)

Os resultados deste estudo foram obtidos pelo exame macroscópico e histopatológico de 3.338 cérebros de bovinos examinados durante o programa de vigilância ativa da encefalopatia espongiforme bovina (BSE) do Ministério da Agricultura, Pecuária e Abastecimento (MAPA), de 2001 a 2005. O trabalho foi realizado no Laboratório de Patologia Veterinária (LPV) da Universidade Federal de Santa Maria (UFSM) que, de 2001 a 2007, foi o laboratório nacional de referência para o diagnóstico da BSE e de outras encefalopatias espongiformes transmissíveis. Macroscopicamente, foram descritas estruturas anatômicas normais (não-lesões), mas que são, com frequência, interpretadas como lesões; lesões sem significado clínico; alterações pós-mortais e artefatos. Esses achados podem confundir e desviar a atenção do patologista durante o exame de rotina do sistema nervoso central (SNC). Da mesma forma, estruturas equivalentes foram descritas no exame histológico. As não-lesões observadas foram corpo pineal, remanescentes embrionários, como a camada germinativa externa do cerebelo, placas subependimárias e aglomerados de neuroblastos nos gânglios da base; ou estruturas circunventriculares, como área de postrema, órgão subcomissural e melanose em leptomeninges e paredes dos vasos. Lesões com pouca ou nenhuma importância relacionadas ao envelhecimento incluíram lipofuscina, hemossiderina, mineralização, hialinização das paredes dos vasos do encéfalo e das meninges. Corpora amylacea foram detectados em processos astrocíticos e corpora arenacea, no corpo pineal. Adicionalmente, foi observada vacuolização no citoplasma de neurônios do núcleo vermelho e do núcleo habenular. Sarcocystis sp. sem reação inflamatória correspondente foi raramente observado. Incluídos nos achados sem manifestação clínica estavam esferóides axonais e manguitos mononucleares perivasculares. Alterações no SNC causadas pelo método de abate, amostragem e fixação podem simular ou obscurecer lesões mais importantes. Aquelas relacionadas ao método de abate incluíram hemorragias causadas em bovinos dessensibilizados pelo dardo cativo ou por punção por faca da medula na articulação atlanto-occipital. Artefatos relacionados à amostragem e manuseio de tecido do SNC consistiram na inclusão de pó de osso no tecido neural em consequência do uso de serra para abrir a caixa craniana; neurônios escuros produzidos pelo manuseio excessivo do cérebro e micro-organismos que contaminaram os tecidos durante a amostragem ou processamento histológico. Alterações autolíticas pós-mortais ou de putrefação incluíram vacuolizações na bainha de mielina, halos claros em torno dos neurônios e oligodendrócitos, aglomerados de bacilos de putrefação dentro dos vasos ou dispersos em todo o tecido cerebral, relacionados ou não a halos claros. Uma alteração autolítica pós-mortal intrigante e relativamente frequente encontrada foi a dissolução parcial da camada de células granulares (CCG) do cerebelo, também referida como conglutinação da CCG ou "état glacé". Devido à escassez de publicações abrangentes neste assunto, esta revisão pretende abordar as principais ciladas que possam aparecer no cérebro de bovinos, na esperança de ajudar outros patologistas a evitar interpretá-las erroneamente.(AU)

Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform Encephalopathy Pathogenesis in Mice.

Conformational conversion of the cellular isoform of prion protein, PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrPC into PrPSc after infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP knockout background, designated Tg(PrPΔOR)/Prnp0/0 mice, did not show reduced susceptibility to RML scrapie prions, with abundant accumulation of PrPScΔOR in their brains. We show here that Tg(PrPΔOR)/Prnp0/0 mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrPScΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrPC into PrPSc after infection with BSE prions. However, Tg(PrPΔOR)/Prnp0/0 mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrPScΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/Prnp0/0 mice than PrPSc in control wild-type mice. Taken together, these results indicate that the OR region of PrPC could play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions.IMPORTANCE Structure-function relationship studies of PrPC conformational conversion into PrPSc are worthwhile to understand the mechanism of the conversion of PrPC into PrPSc We show here that, by inoculating Tg(PrPΔOR)/Prnp0/0 mice with the three different strains of RML, 22L, and BSE prions, the OR region could play a differential role in the conversion of PrPC into PrPSc after infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrPScΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrPScΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrPC into PrPSc after infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions.

Oral Prion Disease Pathogenesis Is Impeded in the Specific Absence of CXCR5-Expressing Dendritic Cells.

After oral exposure, the early replication of certain prion strains upon stromal cell-derived follicular dendritic cells (FDC) in the Peyer's patches in the small intestine is essential for the efficient spread of disease to the brain. However, little is known of how prions are initially conveyed from the gut lumen to establish infection on FDC. Our previous data suggest that mononuclear phagocytes such as CD11c+ conventional dendritic cells play an important role in the initial propagation of prions from the gut lumen into Peyer's patches. However, whether these cells conveyed orally acquired prions toward FDC within Peyer's patches was not known. The chemokine CXCL13 is expressed by FDC and follicular stromal cells and modulates the homing of CXCR5-expressing cells toward the FDC-containing B cell follicles. Here, novel compound transgenic mice were created in which a CXCR5 deficiency was specifically restricted to CD11c+ cells. These mice were used to determine whether CXCR5-expressing conventional dendritic cells propagate prions toward FDC after oral exposure. Our data show that in the specific absence of CXCR5-expressing conventional dendritic cells the early accumulation of prions upon FDC in Peyer's patches and the spleen was impaired, and disease susceptibility significantly reduced. These data suggest that CXCR5-expressing conventional dendritic cells play an important role in the efficient propagation of orally administered prions toward FDC within Peyer's patches in order to establish host infection.IMPORTANCE Many natural prion diseases are acquired by oral consumption of contaminated food or pasture. Once the prions reach the brain they cause extensive neurodegeneration, which ultimately leads to death. In order for the prions to efficiently spread from the gut to the brain, they first replicate upon follicular dendritic cells within intestinal Peyer's patches. How the prions are first delivered to follicular dendritic cells to establish infection was unknown. Understanding this process is important since treatments which prevent prions from infecting follicular dendritic cells can block their spread to the brain. We created mice in which mobile conventional dendritic cells were unable to migrate toward follicular dendritic cells. In these mice the early accumulation of prions on follicular dendritic cells was impaired and oral prion disease susceptibility was reduced. This suggests that prions exploit conventional dendritic cells to facilitate their initial delivery toward follicular dendritic cells to establish host infection.

Diffusion-weighted MRI findings and clinical correlations in sporadic Creutzfeldt-Jakob disease.

The objective of this study is to investigate the hyperintense lesions on diffusion-weighted magnetic resonance imaging (DWI) and its clinical correlation in sporadic Creutzfeldt-Jakob disease (sCJD). Patients who suffered from sCJD and followed up at the Department of Neurology at the General Hospital of the People's Liberation Army during the period of June 1, 2007 to July 1, 2014 were reviewed. The location of the hyperintense lesions on DWI, apparent diffusion coefficient (ADC) values of the hyperintense lesions were correlated with symptoms and clinical course. A total of 58 sCJD patients and ten healthy controls were included. Hyperintense lesions on DWI were observed in all the patients. The patients with basal ganglia (BG) hyperintense lesions on DWI had shorter disease duration and higher incidence of myoclonus (92 versus 44 %) than those without BG hyperintense lesions. The patients with occipital cortex hyperintense lesions on DWI had shorter disease duration between symptom onset and akinetic mutism than those without these lesions. The lower of the BG ADC value the faster presence of akinetic mutism and the shorter disease duration the patients will have. The presence of BG and occipital cortex hyperintense lesions on DWI and BG ADC values is correlated with the clinical course and clinical symptoms.

Electroencephalographic changes in sporadic Creutzfeldt-Jakob disease and correlation with clinical stages: a retrospective analysis.

PURPOSE: To analyze clinical features and EEG changes in patients with sporadic Creutzfeldt-Jakob disease and study the association between different EEG patterns and clinical stages. METHODS: We retrospectively analyzed the clinical features and EEG patterns of 3 patients with clinical stage II and 10 patients with stage III sporadic Creutzfeldt-Jakob disease (EEG n = 17). Chi-square test was used to study the association between EEG features and disease stages. RESULTS: Diffuse slowing of the background was the dominant EEG pattern in stage II disease. All stage III patients showed additional abnormalities, such as frontal intermittent rhythmic delta activity, periodic discharges, and nonperiodic triphasic waves. Periodic discharges had significant association with stage III disease, present in 64% of EEGs in this group. Sixty-seven percentage of periodic discharges had a peculiar pattern labeled by us as posterior-anterior-posterior lag. CONCLUSIONS: The EEG of stage II sporadic Creutzfeldt-Jakob disease is characterized by background slowing while the presence of periodic discharge has a significant association with stage III of the disease. The posterior-anterior-posterior lag of periodic discharge is a new observation.

Foodborne transmission of bovine spongiform encephalopathy to non-human primates results in preclinical rapid-onset obesity.

Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE)-infected female cynomolgus monkeys (Macaca fascicularis). The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c.) infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (ß = 0.915; P<0.0001) which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.

Presence of subclinical infection in gene-targeted human prion protein transgenic mice exposed to atypical bovine spongiform encephalopathy.

The transmission of bovine spongiform encephalopathy (BSE) to humans, leading to variant Creutzfeldt-Jakob disease has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health. Until recently, TSE disease in cattle was thought to be caused by a single agent strain, BSE, also known as classical BSE, or BSE-C. However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. To model the risk to human health, we previously inoculated these two forms of atypical BSE (BASE and BSE-H) into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP) (HuTg) but were unable to detect any signs of TSE pathology in these mice. However, despite the absence of TSE pathology, upon subpassage of some BASE-challenged HuTg mice, a TSE was observed in recipient gene-targeted bovine PrP Tg (Bov6) mice but not in HuTg mice. Disease transmission from apparently healthy individuals indicates the presence of subclinical BASE infection in mice expressing human PrP that cannot be identified by current diagnostic methods. However, due to the lack of transmission to HuTg mice on subpassage, the efficiency of mouse-to-mouse transmission of BASE appears to be low when mice express human rather than bovine PrP.

Case-control study on the risks of BSE infections in Northern Germany.

This study was to identify risk factors for bovine spongiform encephalopathy (BSE) by means of individual case-control data. 43 BSE cases in a defined region in Lower Saxony and Schleswig-Holstein were compared with 84 control animals. Purchase of new breeding stock and cross contamination between feed on the farm did not seem to have influence on the BSE incidence in these regions. The results indicate independent risk patterns. Pattern 1: Cows with high milk yield seemed to be at risk on big farms with adjacent pig production and when they were not fed milk replacer. Pattern 2: Milk replacer (esp. from certain producers) is a risk factor for Non-Red Holstein cattle, low yielding cows and farms without pig production. Pattern 3: Red Holstein cattle not being fed milk replacer have a higher BSE risk than other breeds when they have a low milk yield and live on small farms with pig production. This study, like findings in Bavaria, Lower Saxony and Schleswig-Holstein, strengthens the hypothesis that BSE in Germany was caused by a feed mediated ubiquitous exposure to PrP(sc) during a confined time period. Producers, in need of buying animal derived feed components during that time slot, were more likely to spread the PrP(sc) than others. Their increased risk is not necessarily due to an inadequate purchasing policy, but can also be coincidental. The breed Red Holstein is not the risk factor itself but represents the risk from concentrated feed for animals during a susceptible age period (calves). Therefore, the authors suggest a continuous exclusion of animal-derived fat components from milk replacers.

Foodborne transmission of bovine spongiform encephalopathy to nonhuman primates.

Risk for human exposure to bovine spongiform encephalopathy (BSE)-inducing agent was estimated in a nonhuman primate model. To determine attack rates, incubation times, and molecular signatures, we orally exposed 18 macaques to 1 high dose of brain material from cattle with BSE. Several macaques were euthanized at regular intervals starting at 1 year postinoculation, and others were observed until clinical signs developed. Among those who received ≥5 g BSE-inducing agent, attack rates were 100% and prions could be detected in peripheral tissues from 1 year postinoculation onward. The overall median incubation time was 4.6 years (3.7-5.3). However, for 3 macaques orally exposed on multiple occasions, incubation periods were at least 7-10 years. Before clinical signs were noted, we detected a non-type 2B signature, indicating the existence of atypical prion protein during the incubation period. This finding could affect diagnosis of variant Creutzfeldt-Jakob disease in humans and might be relevant for retrospective studies of positive tonsillectomy or appendectomy specimens because time of infection is unknown.

Early dysfunction of central 5-HT system in a murine model of bovine spongiform encephalopathy.

The hypothesis of an early vulnerability of the serotonergic system to prion infection was investigated in a murine model of bovine spongiform encephalopathy (BSE). Behavioral tests targeted to 5-HT functions were performed in the course of infection to evaluate circadian activity, anxiety-like behavior, pain sensitivity and the 5-HT syndrome. The first behavioral change was a decrease in nocturnal activity detected at 30% of incubation time. Further behavioral alterations including nocturnal hyperactivity, reduced anxiety, hyperalgesia and exaggerated 5-HT syndrome were observed at 60%-70% of incubation time, before the onset of clinical signs. The same tests performed in 5-HT-depleted mice and in prion protein-deficient mice revealed behavioral abnormalities similar in many aspects to those of BSE-infected mice. Histological and biochemical analysis showed alterations of the serotonergic system in BSE-infected and prion protein-deficient mice. These results indicate that BSE infection affects the homeostasis of serotonergic neurons and suggest that the disruption of prion protein normal function contributes to the early pathological changes in our mouse model of BSE. A similar process may occur in the human variant Creutzfeldt-Jacob disease, as suggested by the early symptoms of alterations in mood, sleep and pain sensitivity.

Brainstem auditory evoked potentials in experimentally-induced bovine spongiform encephalopathy.

This study was carried out to evaluate the features of neurological dysfunction in experimentally-induced bovine spongiform encephalopathy (BSE)-infected cattle using brainstem auditory evoked potentials (BAEP). The progressive prolongation of peak latency of waves III and V was observed right-and-left bilaterally at the onset of neurological symptoms. The peak latency of wave V and the I-V interpeak latency (IPL) in BSE cattle 22 and 24 months after intracerebral inoculation were significantly (P<0.05) prolonged compared with the control cattle. In addition, the amplitude of the BAEP waves of the BSE cattle were low compared with the control cattle. Hearing loss occurred in the BSE cattle that showed advanced neurological symptoms such as tremor. It is thought that this BAEP data reflects a functional disorder in the central auditory nerve pathways characteristic of experimentally-induced BSE.