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Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis
INTRODUCTION: Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction durin...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688129/ https://www.ncbi.nlm.nih.gov/pubmed/19196477 http://dx.doi.org/10.1186/cc7710 |
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author | Flierl, Michael A Stahel, Philip F Rittirsch, Daniel Huber-Lang, Markus Niederbichler, Andreas D Hoesel, L Marco Touban, Basel M Morgan, Steven J Smith, Wade R Ward, Peter A Ipaktchi, Kyros |
author_facet | Flierl, Michael A Stahel, Philip F Rittirsch, Daniel Huber-Lang, Markus Niederbichler, Andreas D Hoesel, L Marco Touban, Basel M Morgan, Steven J Smith, Wade R Ward, Peter A Ipaktchi, Kyros |
author_sort | Flierl, Michael A |
collection | PubMed |
description | INTRODUCTION: Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis. METHODS: Using the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls. RESULTS: Placebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group. CONCLUSIONS: Collectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis. |
format | Text |
id | pubmed-2688129 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-26881292009-05-30 Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis Flierl, Michael A Stahel, Philip F Rittirsch, Daniel Huber-Lang, Markus Niederbichler, Andreas D Hoesel, L Marco Touban, Basel M Morgan, Steven J Smith, Wade R Ward, Peter A Ipaktchi, Kyros Crit Care Research INTRODUCTION: Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis. METHODS: Using the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls. RESULTS: Placebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group. CONCLUSIONS: Collectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis. BioMed Central 2009 2009-02-06 /pmc/articles/PMC2688129/ /pubmed/19196477 http://dx.doi.org/10.1186/cc7710 Text en Copyright © 2009 Flierl et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Flierl, Michael A Stahel, Philip F Rittirsch, Daniel Huber-Lang, Markus Niederbichler, Andreas D Hoesel, L Marco Touban, Basel M Morgan, Steven J Smith, Wade R Ward, Peter A Ipaktchi, Kyros Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis |
title | Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis |
title_full | Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis |
title_fullStr | Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis |
title_full_unstemmed | Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis |
title_short | Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis |
title_sort | inhibition of complement c5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688129/ https://www.ncbi.nlm.nih.gov/pubmed/19196477 http://dx.doi.org/10.1186/cc7710 |
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