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.
Wilcockson
David C
DC
CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton, Hampshire, UK.
Campbell
Sandra J
SJ
Anthony
Daniel C
DC
Perry
V Hugh
VH
D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects
D000209:Acute-Phase Proteins; D017931:DNA Primers; D007375:Interleukin-1; D011994:Recombinant Proteins; D016202:N-Methylaspartate