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Volume 14 Supplement 2

Sepsis 2010

Development of Klebsiella pneumoniae B5055-induced mouse model of sepsis-associated brain inflammation in BALB/c mice

Introduction

Incidence of sepsis is continuously increasing in the developing as well as the developed world. Severe sepsis is associated with the development of multiorgan dysfunction syndrome. In addition to other vital organs (that is, lungs, kidneys, heart, or liver), the brain is one of the severely affected organs in sepsis. Autopsy studies from septic patients reveal various cerebral lesions including ischemia, hemorrhage, microthrombi, microabscesses, multifocal necrotizing leukoencephalopathy, and bacterial invasion of the nervous system. Until now no animal model of sepsis has been developed that in a true sense represents the brain inflammation associated with evolving sepsis originating from Gram-negative bacteria. This study comprises development of a mouse model of sepsis-induced brain inflammation.

Methods

A mouse model of sepsis-associated brain inflammation was developed by directly placing a selected dose (102 cfu) of Klebsiella pneumoniae B5055 entrapped in a fibrin-thrombin clot into the peritoneal cavity of mice, while in control group animals only a sterile fibrin clot was kept. Various inflammatory cytokines (that is, IL-1α and TNFα) and other inflammatory markers (that is, malondialdehyde, myeloperoxidase and nitric oxide) in serum and brain were estimated by ELISA, biochemical methods, and histopathology in both the experimental groups.

Results

Bacterial colonies were found to be established in brain on the very first day of sepsis induction in experimental group but no bacteria were observed in sham-operated animals. Along with this, a significant (P < 0.05) increase in neutrophil infiltration into the brain along with significantly (P < 0.05) increased levels of proinflammatory cytokines (TNFα and IL-1α) and other inflammatory mediators like nitric oxide, malondialdehyde, and myeloperoxidase were observed in animals with sepsis. Also the septic animals survived until the 5th day of post-sepsis development, while 100% survival was observed in the sham-operated group on all experimental days without any inflammatory change in the brain as observed by histopathologic examination and estimating the above-mentioned inflammatory parameters.

Conclusions

This mouse model of sepsis-induced brain inflammation may prove helpful to study immunopathogenesis of brain inflammation observed during Gram-negative bacterial sepsis and may also prove helpful to study neuroimmunology of sepsis along with behavioral changes associated with sepsis.

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Correspondence to V Kumar.

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Kumar, V., Sharma, A. Development of Klebsiella pneumoniae B5055-induced mouse model of sepsis-associated brain inflammation in BALB/c mice. Crit Care 14, P4 (2010). https://doi.org/10.1186/cc9107

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Keywords

  • Nitric Oxide
  • Severe Sepsis
  • Malondialdehyde
  • Klebsiella Pneumoniae
  • Neutrophil Infiltration