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The acute inflammatory response in CNS following injection of prion brain homogenate or normal brain homogenate

The acute inflammatory response in CNS following injection of prion brain homogenate or normal brain homogenate
The acute inflammatory response in CNS following injection of prion brain homogenate or normal brain homogenate
The neuropathological hallmarks of end-stage prion disease are vacuolation, neuronal loss, astrocytosis and deposition of PrPSc amyloid. We have also shown that there is an inflammatory response in the brains of scrapie-affected mice from 8 weeks post-injection. In this study we have investigated the acute CNS response to the intracerebral injection of scrapie-affected brain homogenate. The ME7 strain of scrapie (Neuropathogenesis Unit, Edinburgh) was used, and control mice were injected with brain homogenate derived from normal C57BL/6 J mice. One microlitre of 10% w/v ME7 (n=33) and normal brain homogenate (n=28) was injected stereotaxically into the right dorsal hippocampus. Cryostat sections of brains taken at 1, 2, 5, 7, 14 and 28 days post-injection were examined histologically for neuronal loss, and immunocytochemically to study the inflammatory response. This study shows that ME7 is not acutely neurotoxic in vivo. There is also no difference (anova) in the inflammatory response, which peaked between 2 and 5 days and resolved by 4 weeks after intracerebral injection of either ME7 or normal brain homogenate. The well circumscribed inflammatory response seen previously at 8 weeks is therefore a consequence of a disease process rather than a surgical artefact. This disease process may be related to a localized accumulation of PrPSc sufficient to stimulate an inflammatory response which in turn may contribute to neuronal loss. The role of the inflammatory response in chronic neurodegeneration can be usefully studied using this mouse model of prion disease, and this will undoubtedly shed light on the pathogenic mechanisms underlying other chronic neurodegenerative diseases.
mouse, inflammation, microglia, T-cells, cns
0305-1846
20-28
Betmouni, S.
9ac667ca-aa03-4d8e-b7b2-ce6fc34d1121
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Betmouni, S.
9ac667ca-aa03-4d8e-b7b2-ce6fc34d1121
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4

Betmouni, S. and Perry, V.H. (1999) The acute inflammatory response in CNS following injection of prion brain homogenate or normal brain homogenate. Neuropathology and Applied Neurobiology, 25 (1), 20-28. (doi:10.1046/j.1365-2990.1999.00153.x).

Record type: Article

Abstract

The neuropathological hallmarks of end-stage prion disease are vacuolation, neuronal loss, astrocytosis and deposition of PrPSc amyloid. We have also shown that there is an inflammatory response in the brains of scrapie-affected mice from 8 weeks post-injection. In this study we have investigated the acute CNS response to the intracerebral injection of scrapie-affected brain homogenate. The ME7 strain of scrapie (Neuropathogenesis Unit, Edinburgh) was used, and control mice were injected with brain homogenate derived from normal C57BL/6 J mice. One microlitre of 10% w/v ME7 (n=33) and normal brain homogenate (n=28) was injected stereotaxically into the right dorsal hippocampus. Cryostat sections of brains taken at 1, 2, 5, 7, 14 and 28 days post-injection were examined histologically for neuronal loss, and immunocytochemically to study the inflammatory response. This study shows that ME7 is not acutely neurotoxic in vivo. There is also no difference (anova) in the inflammatory response, which peaked between 2 and 5 days and resolved by 4 weeks after intracerebral injection of either ME7 or normal brain homogenate. The well circumscribed inflammatory response seen previously at 8 weeks is therefore a consequence of a disease process rather than a surgical artefact. This disease process may be related to a localized accumulation of PrPSc sufficient to stimulate an inflammatory response which in turn may contribute to neuronal loss. The role of the inflammatory response in chronic neurodegeneration can be usefully studied using this mouse model of prion disease, and this will undoubtedly shed light on the pathogenic mechanisms underlying other chronic neurodegenerative diseases.

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More information

Published date: January 1999
Keywords: mouse, inflammation, microglia, T-cells, cns

Identifiers

Local EPrints ID: 55855
URI: http://eprints.soton.ac.uk/id/eprint/55855
ISSN: 0305-1846
PURE UUID: 77e0bc07-a15d-46c8-bf3d-6684df90e957

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Date deposited: 21 Aug 2008
Last modified: 13 Mar 2019 20:35

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Contributors

Author: S. Betmouni
Author: V.H. Perry

University divisions

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