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Identification of the end stage of scrapie using infected neural grafts.


Brandner, S; Isenmann, S; Kühne, G; Aguzzi, A (1998). Identification of the end stage of scrapie using infected neural grafts. Brain Pathology, 8(1):19-27.

Abstract

Although the formal pathogenesis of spongiform encephalopathies has been described in detail, it is not known whether the infectious agent targets primarily neurons, glial cells, or both. To address this question, we have transplanted transgenic embryonic neural tissue overexpressing PrP(c) into the forebrain of Prnp -knockout mice, and infected it with scrapie prions. After infection, grafts developed severe spongiform encephalopathy. As the infected hosts were not clinically affected, we were able to prolong the experiment and to assess changes in the graft over periods of time, which vastly exceeded the normal life span of scrapie-infected mice. Sequential contrast-enhanced magnetic resonance imaging (MRI) revealed progressive impairment of blood-brain barrier properties in infected grafts. However, loss of astrocytes was not observed. Subtotal neuronal loss occurred during the progression of the disease in the grafts, reactive astrocytes persisted until the terminal stage of disease. We conclude that scrapie encephalopathy primarily leads to neuronal death, while degeneration of astrocytes does not occur. Functional impairment of the blood-brain barrier suggests involvement of astrocytes and endothelial cells in the pathological process.

Although the formal pathogenesis of spongiform encephalopathies has been described in detail, it is not known whether the infectious agent targets primarily neurons, glial cells, or both. To address this question, we have transplanted transgenic embryonic neural tissue overexpressing PrP(c) into the forebrain of Prnp -knockout mice, and infected it with scrapie prions. After infection, grafts developed severe spongiform encephalopathy. As the infected hosts were not clinically affected, we were able to prolong the experiment and to assess changes in the graft over periods of time, which vastly exceeded the normal life span of scrapie-infected mice. Sequential contrast-enhanced magnetic resonance imaging (MRI) revealed progressive impairment of blood-brain barrier properties in infected grafts. However, loss of astrocytes was not observed. Subtotal neuronal loss occurred during the progression of the disease in the grafts, reactive astrocytes persisted until the terminal stage of disease. We conclude that scrapie encephalopathy primarily leads to neuronal death, while degeneration of astrocytes does not occur. Functional impairment of the blood-brain barrier suggests involvement of astrocytes and endothelial cells in the pathological process.

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31 citations in Web of Science®
33 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 January 1998
Deposited On:11 Feb 2008 12:26
Last Modified:05 Apr 2016 12:20
Publisher:Wiley-Blackwell
ISSN:1015-6305
Publisher DOI:https://doi.org/10.1111/j.1750-3639.1998.tb00130.x
Related URLs:http://www.blackwell-synergy.com/doi/abs/10.1111/j.1750-3639.1998.tb00130.x
PubMed ID:9458163

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