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

2021 ◽  
Vol 22 (21) ◽  
pp. 11310
Author(s):  
Ivett Ackermann ◽  
Reiner Ulrich ◽  
Kerstin Tauscher ◽  
Olanrewaju I. Fatola ◽  
Markus Keller ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Infectious Agent ◽  
Pharmaceutical Products ◽  
Oral Exposure ◽  
Mouse Bioassay ◽  
Spongiform Encephalopathy ◽  
Post Inoculation ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal

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.

scholarly journals Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy

2007 ◽  
Vol 88 (3) ◽  
pp. 1048-1055 ◽  
Author(s):  
Christine Hoffmann ◽  
Ute Ziegler ◽  
Anne Buschmann ◽  
Artur Weber ◽  
Leila Kupfer ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Autonomic Nervous System ◽  
Bovine Spongiform Encephalopathy ◽  
Spongiform Encephalopathy ◽  
Thoracic Spinal Cord ◽  
Diagnostic Strategies ◽  
Autonomic Nervous ◽  
Thoracic Spinal ◽  
The Central Nervous System

To elucidate the still-unknown pathogenesis of bovine spongiform encephalopathy (BSE), an oral BSE challenge and sequential kill study was carried out on 56 calves. Relevant tissues belonging to the peripheral and central nervous system, as well as to the lymphoreticular tract, from necropsied animals were analysed by highly sensitive immunohistochemistry and immunoblotting techniques to reveal the presence of BSE-associated pathological prion protein (PrPSc) depositions. Our results demonstrate two routes involving the autonomic nervous system through which BSE prions spread by anterograde pathways from the gastrointestinal tract (GIT) to the central nervous system (CNS): (i) via the coeliac and mesenteric ganglion complex, splanchnic nerves and the lumbal/caudal thoracic spinal cord (representing the sympathetic GIT innervation); and (ii) via the Nervus vagus (parasympathetic GIT innervation). The dorsal root ganglia seem to be subsequently affected, so it is likely that BSE prion invasion of the non-autonomic peripheral nervous system (e.g. sciatic nerve) is a secondary retrograde event following prion replication in the CNS. Moreover, BSE-associated PrPSc was already detected in the brainstem of an animal 24 months post-infection, which is 8 months earlier than reported previously. These findings are important for the understanding of BSE pathogenesis and for the development of new diagnostic strategies for this infectious disease.

scholarly journals Glycosylation of PrPC Determines Timing of Neuroinvasion and Targeting in the Brain following Transmissible Spongiform Encephalopathy Infection by a Peripheral Route

2010 ◽  
Vol 84 (7) ◽  
pp. 3464-3475 ◽  
Author(s):  
Enrico Cancellotti ◽  
Barry M. Bradford ◽  
Nadia L. Tuzi ◽  
Raymond D. Hickey ◽  
Debbie Brown ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transmissible Spongiform Encephalopathy ◽  
Disease Onset ◽  
Infectious Agent ◽  
Spongiform Encephalopathy ◽  
Infectious Process ◽  
Key Factor ◽  
The Central Nervous System ◽  
The Brain

ABSTRACT Transmissible spongiform encephalopathy (TSE) infectivity naturally spreads from site of entry in the periphery to the central nervous system where pathological lesions are formed. Several routes and cells within the host have been identified as important for facilitating the infectious process. Expression of the glycoprotein cellular PrP (PrPC) is considered a key factor for replication of infectivity in the central nervous system (CNS) and its transport to the brain, and it has been suggested that the infectious agent propagates from cell to cell via a domino-like effect. However, precisely how this is achieved and what involvement the different glycoforms of PrP have in these processes remain to be determined. To address this issue, we have used our unique models of gene-targeted transgenic mice expressing different glycosylated forms of PrP. Two TSE strains were inoculated intraperitoneally into these mice to assess the contribution of diglycosylated, monoglycosylated, and unglycosylated PrP in spreading of infectivity to the brain. This study demonstrates that glycosylation of host PrP has a profound effect in determining the outcome of disease. Lack of diglycosylated PrP slowed or prevented disease onset after peripheral challenge, suggesting an important role for fully glycosylated PrP in either the replication of the infectious agent in the periphery or its transport to the CNS. Moreover, mice expressing unglycosylated PrP did not develop clinical disease, and mice expressing monoglycosylated PrP showed strikingly different neuropathologic features compared to those expressing diglycosylated PrP. This demonstrates that targeting in the brain following peripheral inoculation is profoundly influenced by the glycosylation status of host PrP.

scholarly journals Syringomyelia in demyelinating disease of the central nervous system: Report of two cases

2011 ◽  
Vol 139 (9-10) ◽  
pp. 657-660 ◽  
Author(s):  
Dejan Savic ◽  
Slobodan Vojinovic ◽  
Mirjana Spasic ◽  
Zoran Peric ◽  
Stevo Lukic
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Magnetic Resonance ◽  
Demyelinating Disease ◽  
Clinical Signs ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
The Central Nervous System

Introduction. Syringomyelia is a cavitary extension inside the spinal cord which can be either symptomatic or congenitally-idiopathic. Syringomyelia during the course of the disease in patients presenting with clinically definite multiple sclerosis was described earlier. Syringomyelia in patients presenting with a clinically isolated syndrome suggestive of multiple sclerosis is unusual. Case Outline. We present two patients presenting with demy-elinating disease of the central nervous system with syringomyelia in the cervical and thoracic spinal cord. We did not find classical clinical signs of syringomyelia in our patients, but we disclosed syringomyelia incidentally during magnetic resonance exploration. Magnetic resonance exploration using the gadolinium contrast revealed the signs of active demyelinating lesions in the spinal cord in one patient but not in the other. Conclusion. Syringomyelia in demyelinating disease of the central nervous system opens the question whether it is a coincidental finding or a part of clinical features of the disease. Differentiation of the significance of syringomyelia finding in these patients plays a role in the choice of treatment concept in such patients.

scholarly journals Chronic Wasting Disease

2005 ◽  
Vol 42 (5) ◽  
pp. 530-549 ◽  
Author(s):  
E. S. Williams
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chronic Wasting Disease ◽  
Oral Exposure ◽  
Spongiform Encephalopathy ◽  
Lymphoid Tissues ◽  
Wasting Disease ◽  
Peripheral Tissues ◽  
Prolonged Incubation ◽  
Free Ranging

Chronic wasting disease (CWD) is a unique transmissible spongiform encephalopathy (TSE) of mule deer ( Odocoileus hemionus), white-tailed deer ( O. virginianus), and Rocky Mountain elk ( Cervus elaphus nelsoni). The natural history of CWD is incompletely understood, but it differs from scrapie and bovine spongiform encephalopathy (BSE) by virtue of its occurrence in nondomestic and free-ranging species. CWD has many features in common with scrapie, including early widespread distribution of disease-associated prion protein (PrPd) in lymphoid tissues, with later involvement of central nervous system (CNS) and peripheral tissues. This distribution likely contributes to apparent efficiency of horizontal transmission and, in this, is similar to scrapie and differs from BSE. Clinical features and lesions of CWD are qualitatively similar to the other animal TSEs. Microscopically, marked spongiform lesions occur in the central nervous system (CNS) after a prolonged incubation period and variable course of clinical disease. During incubation, PrPd can be identified in tissues by antibody-based detection systems. Although CWD can be transmitted by intracerebral inoculation to cattle, sheep, and goats, ongoing studies have not demonstrated that domestic livestock are susceptible via oral exposure, the presumed natural route of exposure to TSEs. Surveillance efforts for CWD in captive and free-ranging cervids will continue in concert with similar activities for scrapie and BSE. Eradication of CWD in farmed cervids is the goal of state, federal, and industry programs, but eradication of CWD from free-ranging populations of cervids is unlikely with currently available management techniques.

Alteration of posttraumatic ischemia in experimental spinal cord trauma by a central nervous system depressant

1979 ◽  
Vol 50 (2) ◽  
pp. 207-216 ◽  
Author(s):  
Howard J. Senter ◽  
Joan L. Venes ◽  
John S. Kauer
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Blood Flow ◽  
Nervous System ◽  
Thoracic Spinal Cord ◽  
Content Type ◽  
Thoracic Spinal ◽  
Gamma Hydroxybutyrate ◽  
Central Nervous System Depressant ◽  
Experimental Injury

✓ Blood flow after severe experimental injury to the thoracic spinal cord was studied in cats, using a modification of the hydrogen clearance technique. Gamma hydroxybutyrate, a central nervous system depressant, was shown to markedly alter the ischemic response to injury if given during the early posttraumatic period. Other vasoactive drugs investigated had no effect on posttraumatic ischemia. Therapeutic intervention during the early posttraumatic period aimed at increasing blood flow while decreasing the metabolic requirements of the injured cord may prove of value in reversing or limiting some elements of long-tract dysfunction due to the secondary ischemic insult.

scholarly journals Neuronal Vacuolization in Feline Panleukopenia Virus Infection

2017 ◽  
Vol 55 (2) ◽  
pp. 294-297 ◽  
Author(s):  
Vanessa M. Pfankuche ◽  
Wendy K. Jo ◽  
Erhard van der Vries ◽  
Nicole Jungwirth ◽  
Stephan Lorenzen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Thoracic Spinal Cord ◽  
Feline Panleukopenia Virus ◽  
Thoracic Spinal ◽  
High Mitotic Activity ◽  
The Central Nervous System ◽  
Generation Sequencing ◽  
Specific Sequences

Feline panleukopenia virus (FPV) infections are typically associated with anorexia, vomiting, diarrhea, neutropenia, and lymphopenia. In cases of late prenatal or early neonatal infections, cerebellar hypoplasia is reported in kittens. In addition, single cases of encephalitis are described. FPV replication was recently identified in neurons, although it is mainly found in cells with high mitotic activity. A female cat, 2 months old, was submitted to necropsy after it died with neurologic deficits. Besides typical FPV intestinal tract changes, multifocal, randomly distributed intracytoplasmic vacuoles within neurons of the thoracic spinal cord were found histologically. Next-generation sequencing identified FPV-specific sequences within the central nervous system. FPV antigen was detected within central nervous system cells, including the vacuolated neurons, via immunohistochemistry. In situ hybridization confirmed the presence of FPV DNA within the vacuolated neurons. Thus, FPV should be considered a cause for neuronal vacuolization in cats presenting with ataxia.

scholarly journals High-grade astrocytoma with piloid features (HGAP): the Charité experience with a new central nervous system tumor entity

2021 ◽  
Author(s):  
Katja Bender ◽  
Eilís Perez ◽  
Mihaela Chirica ◽  
Julia Onken ◽  
Johannes Kahn ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Central Nervous System ◽  
Nervous System ◽  
World Health ◽  
Central Nervous System Tumor ◽  
High Grade ◽  
Thoracic Spinal Cord ◽  
High Grade Astrocytoma ◽  
Tumor Entity

Abstract Purpose High-grade astrocytoma with piloid features (HGAP) is a recently described brain tumor entity defined by a specific DNA methylation profile. HGAP has been proposed to be integrated in the upcoming World Health Organization classification of central nervous system tumors expected in 2021. In this series, we present the first single-center experience with this new entity. Methods During 2017 and 2020, six HGAP were identified. Clinical course, surgical procedure, histopathology, genome-wide DNA methylation analysis, imaging, and adjuvant therapy were collected. Results Tumors were localized in the brain stem (n = 1), cerebellar peduncle (n = 1), diencephalon (n = 1), mesencephalon (n = 1), cerebrum (n = 1) and the thoracic spinal cord (n = 2). The lesions typically presented as T1w hypo- to isointense and T2w hyperintense with inhomogeneous contrast enhancement on MRI. All patients underwent initial surgical intervention. Three patients received adjuvant radiochemotherapy, and one patient adjuvant radiotherapy alone. Four patients died of disease, with an overall survival of 1.8, 9.1, 14.8 and 18.1 months. One patient was alive at the time of last follow-up, 14.6 months after surgery, and one patient was lost to follow-up. Apart from one tumor, the lesions did not present with high grade histology, however patients showed poor clinical outcomes. Conclusions Here, we provide detailed clinical, neuroradiological, histological, and molecular pathological information which might aid in clinical decision making until larger case series are published. With the exception of one case, the tumors did not present with high-grade histology but patients still showed short intervals between diagnosis and tumor progression or death even after extensive multimodal therapy.

Technological Maturity and Systematic Review of Medicinal Plants with Pharmacological Activity in the Central Nervous System

2021 ◽  
Vol 15 ◽  
Author(s):  
Eduardo Muniz Santana Bastos ◽  
Victor Diogenes Amaral da Silva ◽  
Silvia Lima Costa ◽  
Samira Abdallah Hanna
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Medicinal Plants ◽  
Pharmacological Activity ◽  
Pharmaceutical Products ◽  
Technology Readiness ◽  
Industrial Property ◽  
Scientific Exploration ◽  
The Central Nervous System ◽  
Pharmaceutical Industries

Background: Medicinal plants present activities against neurodegenerative diseases with potential for the pharmaceutical industries. Therefore, the objective of this study was to investigate the current panorama of patents and articles of Brazilian medicinal plants with pharmacological activities in the Central Nervous System (CNS), regarding such aspects as: the number of patents by countries, areas of knowledge and technological maturity. Method: We carry out a technological exploration on the Questel Orbit® platform with the descriptors: Agave sisalana P., Amburana cearenses A., Dimorphandra mollis B., Jatropha curcas L, Poincianella pyramidalis T. and Prosopis juliflora (Sw.) DC. with pharmacological activity, and a scientific exploration in PubMed and Science Direct associated with the CNS in the title, abstract and methodology. Results: A total of 642 patents were identified between the years 1999-2019. India, China and Brazil are highlighted, 6th place, out of a total of 48 countries. Of these, 30 patents were not in the National Institute of Industrial Property and 10% are Brazilian in biotechnology and pharmaceutical products. Eleven articles were used in PubMed and Science Direct with scientific domains (anticancer, neuroprotection and anti-inflammatory). The Federal University of Bahia is highlighted, showing Technology Readiness Levels (TRL4), basic skills of pre-clinical research. Conclusion: Brazilian public universities have a significant role in the scientific, technological and innovative development of therapeutic assets for CNS.

Control Points To Reduce Movement of Central Nervous System Tissue during Beef Slaughter

2017 ◽  
Vol 80 (2) ◽  
pp. 355-360
Author(s):  
J. L. Aalhus ◽  
R. D. Thacker ◽  
I. L. Larsen ◽  
J. C. Roberts ◽  
M. A. Price ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cold Water ◽  
Effective Means ◽  
Hot Water ◽  
Spongiform Encephalopathy ◽  
Cross Contamination ◽  
Central Nervous System Tissue ◽  
Before And After ◽  
Disease Variant

ABSTRACT Consumption of central nervous system tissue (CNST) from cattle with bovine spongiform encephalopathy (BSE) is thought to cause the human neurological disease, variant Creutzfeldt-Jacob disease. To identify points of cross-contamination of beef carcasses with CNST, 55 young beef cattle were slaughtered and processed through a federally inspected multispecies abattoir. The objectives of this study were to evaluate CNST spread following the placement of a plug in the penetration site of the skull after captive bolt stunning, to evaluate cross-contamination of carcasses before and after splitting, to compare the effects of hot water pasteurization (84°C for 10 s) versus cold water wash (10°C for 30 s) for reducing CNST on the carcass, and to examine other possible sources of cross-contamination in the abattoir. Results indicated that the use of a plastic plug reduced CNST contamination near the bolt penetration site. This study also confirmed that carcass splitting resulted in an increase in CNST contamination at various areas of the carcass. Hot water pasteurization appeared to be an effective means of removing CNST contamination from carcasses in most of the areas sampled.

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