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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2024

Open Access 01-12-2024 | Central Nervous System Trauma | Research

Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury

Authors: Ali Shad, Sarah S. J. Rewell, Matthew Macowan, Natasha Gandasasmita, Jiping Wang, Ke Chen, Ben Marsland, Terence J. O’Brien, Jian Li, Bridgette D. Semple

Published in: Journal of Neuroinflammation | Issue 1/2024

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Abstract

Pneumonia is a common comorbidity in patients with severe traumatic brain injury (TBI), and is associated with increased morbidity and mortality. In this study, we established a model of intratracheal Klebsiella pneumoniae administration in young adult male and female mice, at 4 days following an experimental TBI, to investigate how K. pneumoniae infection influences acute post-TBI outcomes. A dose-response curve determined the optimal dose of K. pneumoniae for inoculation (1 x 10^6 colony forming units), and administration at 4 days post-TBI resulted in transient body weight loss and sickness behaviors (hypoactivity and acute dyspnea). K. pneumoniae infection led to an increase in pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid at 24 h post-infection, in both TBI and sham (uninjured) mice. By 7 days, when myeloperoxidase + neutrophil numbers had returned to baseline in all groups, lung histopathology was observed with an increase in airspace size in TBI + K. pneumoniae mice compared to TBI + vehicle mice. In the brain, increased neuroinflammatory gene expression was observed acutely in response to TBI, with an exacerbated increase in Ccl2 and Hmox1 in TBI + K. pneumoniae mice compared to either TBI or K. pneumoniae alone. However, the presence of neuroinflammatory immune cells in the injured brain, and the extent of damage to cortical and hippocampal brain tissue, was comparable between K. pneumoniae and vehicle-treated mice by 7 days. Examination of the fecal microbiome across a time course did not reveal any pronounced effects of either injury or K. pneumoniae on bacterial diversity or abundance. Together, these findings demonstrate that K. pneumoniae lung infection after TBI induces an acute and transient inflammatory response, primarily localized to the lungs with some systemic effects. However, this infection had minimal impact on secondary injury processes in the brain following TBI. Future studies are needed to evaluate the potential longer-term consequences of this dual-hit insult.
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Metadata
Title
Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury
Authors
Ali Shad
Sarah S. J. Rewell
Matthew Macowan
Natasha Gandasasmita
Jiping Wang
Ke Chen
Ben Marsland
Terence J. O’Brien
Jian Li
Bridgette D. Semple
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2024
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-024-03093-9

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