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The systemic and local acute phase response following acute brain injury

The systemic and local acute phase response following acute brain injury
The systemic and local acute phase response following acute brain injury
It is not known whether acute brain injury results in a systemic acute phase response (APR) or whether an APR influences outcome after an insult to the CNS. The present study sought to establish whether brain injury elicits a systemic or local APR. The expression of acute phase protein (APP) mRNA in liver and brain tissues was measured by Taqman reverse transcriptase-polymerase chain reaction after an excitotoxic lesion in the striatum or challenge with a proinflammatory cytokine. N-methyl-d-aspartate (NMDA)–induced brain lesion did not elicit a systemic APR. In contrast, proinflammatory challenge with mouse recombinant interleukin-1beta (mrIL-1beta) resulted in a significant hepatic APP mRNA expression within 6 hours. Thus, an inflammatory challenge that results in a meningitis leads to a hepatic APR, whereas acute brain injury alone, with no evidence of a meningitis, does not produce an APR. This is surprising because NMDA leads to an increase in endogenous IL-1beta synthesis. This suggests that the brain has an endogenous antiinflammatory mechanism, which protects against the spread of inflammation after an acute injury. In the brain, both excitotoxic lesions and proinflammatory challenge resulted in a profound parenchymal upregulation of APP mRNA after 6 and 12 hours in the injected hemisphere. These results suggest that the local APR may play a role as an antiinflammatory mechanism. These findings indicate a potentially pivotal role for peripheral and local APP production on outcome after brain injury.
acute phase response, brain injury, N-methyl-d-aspartate, interleukin-1beta
0271-678X
318-326
Wilcockson, David C.
ba84a5a7-c06c-4d54-ba4d-1113c607e28e
Campbell, Sandra J.
5c85ee6c-22f6-47d9-9e11-21173a9323a5
Anthony, Daniel C.
928249fa-dcf4-4088-b95b-ce14c719164d
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Wilcockson, David C.
ba84a5a7-c06c-4d54-ba4d-1113c607e28e
Campbell, Sandra J.
5c85ee6c-22f6-47d9-9e11-21173a9323a5
Anthony, Daniel C.
928249fa-dcf4-4088-b95b-ce14c719164d
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4

Wilcockson, David C., Campbell, Sandra J., Anthony, Daniel C. and Perry, V. Hugh (2002) The systemic and local acute phase response following acute brain injury. Journal of Cerebral Blood Flow & Metabolism, 22 (3), 318-326. (doi:10.1097/00004647-200203000-00009).

Record type: Article

Abstract

It is not known whether acute brain injury results in a systemic acute phase response (APR) or whether an APR influences outcome after an insult to the CNS. The present study sought to establish whether brain injury elicits a systemic or local APR. The expression of acute phase protein (APP) mRNA in liver and brain tissues was measured by Taqman reverse transcriptase-polymerase chain reaction after an excitotoxic lesion in the striatum or challenge with a proinflammatory cytokine. N-methyl-d-aspartate (NMDA)–induced brain lesion did not elicit a systemic APR. In contrast, proinflammatory challenge with mouse recombinant interleukin-1beta (mrIL-1beta) resulted in a significant hepatic APP mRNA expression within 6 hours. Thus, an inflammatory challenge that results in a meningitis leads to a hepatic APR, whereas acute brain injury alone, with no evidence of a meningitis, does not produce an APR. This is surprising because NMDA leads to an increase in endogenous IL-1beta synthesis. This suggests that the brain has an endogenous antiinflammatory mechanism, which protects against the spread of inflammation after an acute injury. In the brain, both excitotoxic lesions and proinflammatory challenge resulted in a profound parenchymal upregulation of APP mRNA after 6 and 12 hours in the injected hemisphere. These results suggest that the local APR may play a role as an antiinflammatory mechanism. These findings indicate a potentially pivotal role for peripheral and local APP production on outcome after brain injury.

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More information

Published date: March 2002
Keywords: acute phase response, brain injury, N-methyl-d-aspartate, interleukin-1beta

Identifiers

Local EPrints ID: 56736
URI: http://eprints.soton.ac.uk/id/eprint/56736
ISSN: 0271-678X
PURE UUID: 420dc08f-949c-4802-aa79-35fe91329c01

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Date deposited: 07 Aug 2008
Last modified: 15 Mar 2024 11:03

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Contributors

Author: David C. Wilcockson
Author: Sandra J. Campbell
Author: Daniel C. Anthony
Author: V. Hugh Perry

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