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Critical Care

Volume 17 Supplement 4

Sepsis 2013

Open Access

Evaluation of inflammatory parameters and cognitive impairment in a murine model of Pseudomonas aeruginosa pneumosepsis

  • Flora Magno1,
  • Danielle O Nascimento1,
  • Pedro CB Alexandre1,
  • Patrícia A Reis1,
  • Patrícia T Bozza1,
  • Hugo C Castro-Faria-Neto1 and
  • Fernando A Bozza1
Critical Care201317(Suppl 4):P104

https://doi.org/10.1186/cc13003

Published: 5 November 2013

Keywords

Pseudomonas AeruginosaMeropenemBronchoalveolar Lavage FluidSepsis PatientAcute Inflammatory Response

Background

Sepsis is a severe medical condition characterized by systemic inflammatory response secondary to infection, which frequently progresses to multiple organ dysfunction and death. It is currently the leading cause of death in ICUs worldwide. The most frequent source of infection in sepsis is the lung with a high lethality rate. Pseudomonas aeruginosa is one of the most common pathogens found in sepsis patients. Cognitive impairment is a significant consequence of sepsis reported among survivors. The encephalopathy associated with systemic inflammation is not well understood so the development of new clinical relevant models to help understand this sequelae is important. In this study we aimed to evaluate acute inflammatory markers and establish a long-term consequence in a murine model of pneumosepsis.

Materials and methods

C57/BL6 mice were submitted to intratracheal instillation of 105 colony-forming units of P. aeruginosa. Six hours later the bronchoalveolar lavage fluid was collected for cell migration, protein (BCA method) and cytokine (ELISA) analysis. Caudal vein blood samples were collected for cell counting. Another group of animals had their lungs perfused for myeloperoxidase quantification and histological analysis. Evan's blue dye method was used for the assessment of lung permeability. The survival rate of animals submitted to P. aeruginosa instillation was observed daily during 7 days. This group of animals received a single dose of antibiotic meropenem (30 mg/kg), 6 hours after pneumonia induction. Cognitive damage was evaluated through the freezing test.

Results

Our results showed that P. aeruginosa infection caused an expressive recruitment of leukocytes, mainly neutrophils to the lung. Myeloperoxidase, a marker for neutrophil migration, was significantly increased in the lungs of animals instilled with P. aeruginosa. The animals instilled with P. aeruginosa also showed a significant increase in IL-6, KC and protein levels. Histological analysis showed an intense cell infiltrate in the lung tissue and the survival rate was extensively lower in P. aeruginosa infected mice. Additionally, the animals submitted to pneumosepsis had a loss of aversive memory 13 days after pneumonia induction and this loss remained 50 days later.

Conclusions

Our study demonstrates the acute inflammatory response to P. aeruginosa lung infection and indicates that possibly this pneumonia model can cause irreversible cognitive impairment. Our results reveal a possible experimental model for the study of encephalopathy associated with systemic inflammation.

Declarations

Acknowledgements

Financial support: CNPq, FAPERJ and FIOCRUZ.

Authors’ Affiliations

(1)
Immunopharmacology Laboratory, IOC/FIOCRUZ, Brazil

Copyright

© Magno 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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