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Critical Care

Volume 17 Supplement 4

Sepsis 2013

Open Access

CD40 expression in the hippocampus and its role in blood-brain barrier permeability, neutrophil infiltration and oxidative stress: implication for brain damage associated with sepsis in rats

  • Monique Michels1,
  • Lucinéia G Danielski1,
  • Andriele A da Silva Vieira1,
  • Luiz Carlos Vieira1,
  • Drielly Florentino1,
  • André Laurenano1,
  • Francielle Mina2,
  • Francieli Vuolo3,
  • Dhébora M Dall'Igna3,
  • Letícia Galant3,
  • João Quevedo2,
  • Felipe Dal-Pizzol3 and
  • Fabrícia Petronilho1
Critical Care201317(Suppl 4):P77

https://doi.org/10.1186/cc12976

Published: 5 November 2013

Keywords

Oxidative DamageCD40 ExpressionCell InfiltrationPotential Therapeutic TargetProtein Carbonylation

Background

Sepsis is a clinical condition resulting from the excessive inflammatory response of the host against an infectious agent and is associated with high morbidity and mortality in patients in ICUs. In sepsis the brain can be targeted, associated with mental damage and decline, impaired attention, disorientation, delirium and coma. It has been seen that the permeability of the blood-brain barrier (BBB) is associated with septic encephalopathy, allowing cell infiltration and increased oxidative stress. Accordingly, such events can be potentiated through the involvement of molecules that when activated perpetuate the inflammatory response and the breaking of the BBB, and it is possible to postulate that the CD40 molecule may be involved by being under increased expression in microglia in inflammatory events occurring systemically. The aim of this study therefore is to evaluate the role of CD40 in the breakdown of the BBB, cell infiltration and oxidative damage in the brain of rats with sepsis.

Materials and methods

Male Wistar rats were subjected to cecal ligation and puncture (CLP) to induce sepsis. The animals (n = 10) were divided into sham, CLP, CLP + 1 ng, CLP + 10 ng and CLP + 100 ng anti-CD40 antibody administered intracerebroventricularly. The rats were killed at 24 hours for assessment of oxidative damage in lipids (TBARS), damage to proteins by protein carbonylation, nitrite/nitrate concentration (NO), myeloperoxidase (MPO) and breakdown of the BBB. The other group was subjected to CLP and after 24 hours they were killed and the hippocampus removed to analyse expression of CD40 and CD40L by western blotting. Data were evaluated by ANOVA and post-hoc Tukey test with significance P < 0.05.

Results

Our results show that in the most effective dose of 100 ng/kg anti-CD40 showed a decrease in the breakdown of the BBB, MPO, nitrite/nitrate concentration and TBARS. A dose of 1 ng/kg was effective only in the reduction of nitrite/nitrate concentration and 10 ng/kg was not effective in TBARS and carbonyl. Western blotting analysis showed increased expression of CD40 and CD40L in CLP animals when compared with sham.

Conclusions

Modulation of the levels of CD40 may represent a potential therapeutic target in sepsis.

Declarations

Acknowledgements

CAPES, CNPq, UNESC and UNISUL.

Authors’ Affiliations

(1)
Laboratório de Fisiopatologia Clínica e Experimental, UNISUL, Tubarão, Brazil
(2)
Laboratório de Neurociências, UNESC, Criciúma, Brazil
(3)
Laboratório de Fisiopatologia Experimental, UNESC, Criciúma, Brazil

Copyright

© Michels et al.; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. 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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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