Short CommunicationExperimental traumatic brain injury does not lead to lung infection
Graphical abstract
Introduction
Traumatic brain injury (TBI) affects ~10 million people worldwide annually, and is a leading cause of mortality and morbidity (Blennow et al., 2012; Humphreys et al., 2013). TBI can result in immunosuppression that leads to an impaired capacity to defend against infectious agents, particularly during the first few days to weeks following the injury (Kong et al., 2014; Marks et al., 2013; Mrakovcic-Sutic et al., 2010; Sun et al., 2018). Infections of the lower respiratory tract account for ~40% of all infections in hospitalized TBI patients, and are particularly common during these subacute stages (Alharfi et al., 2014; Ho et al., 2018; Kourbeti et al., 2012; Mrakovcic-Sutic et al., 2010; Piek et al., 1992). Given that systemic infections have been shown to negatively affect recovery and increase the risk of mortality following TBI, it is important that the understanding of the mechanisms and risk factors for post-traumatic pulmonary infections is improved (Alharfi et al., 2014; Ho et al., 2018; Kourbeti et al., 2012; Mrakovcic-Sutic et al., 2010; Piek et al., 1992). Though animal studies have demonstrated that systemic challenge by lipopolysaccharide (i.e. an endotoxin commonly used to mimic bacterial infection) post-TBI resulted in worse neuroinflammation and neurological outcomes (Collins-Praino et al., 2018; Corrigan et al., 2017; Hang et al., 2004), the occurrence of spontaneous post-traumatic infection and its influence on TBI pathobiology is grossly understudied. Of relevance, stroke is a brain injury that also leads to post-injury infections, and can feature pathophysiological similarities with TBI such as neuroinflammation, oxidative stress, excitotoxicity, edema, and immunosuppression (Bramlett and Dietrich, 2004; Jayaraj et al., 2019; Shim and Wong, 2016; Sun et al., 2018; Werner and Engelhard, 2007). Notably, mice given an ischemic stroke had high rates of spontaneous lung infection (Stanley et al., 2016). Accordingly, here we employed a rat lateral fluid percussion injury (LFPI) model to investigate lung infection during the acute and subacute stages of a severe TBI.
Section snippets
Animals
Forty-one male Sprague Dawley rats were obtained from the Alfred Medical Research and Education Precinct (AMREP) Animal Centre (Australia). Rats were 11–13 weeks old and randomized to receive either sham-injury or TBI. Nine rats died at the time of LFPI and five rats were euthanized during the recovery period, and were therefore excluded from the study. Surviving rats were assigned to 24 h (sham = 6, LFPI = 4), 48 h (sham = 4, LFPI = 4), and 7d (sham = 5, LFPI = 4) recovery endpoints for
LFPI does not induce spontaneous lung infection
At 24 h, 48 h, or 7 d post-LFPI, analysis of bacterial load showed minimal numbers of bacterial c.f.u. in the lung tissue of all groups, and t-test indicated that there was no statistical difference between the sham and LFPI groups for all recovery times (p > .05; Fig. 1.).
LFPI does not affect spleen to body weight ratio
The spleen to body weight ratio (i.e., an indicator of systemic immunosuppression) was calculated in the 7 d group, and t-test found no statistical difference between Sham and LFPI groups (p > .05; Fig. 2).
Discussion
Nosocomial pneumonia is a common complication in TBI patients (Bronchard et al., 2004; Hu et al., 2017; Kourbeti et al., 2012). However, the relationship between TBI and increased risk of lung infection is poorly understood. This study aimed to provide some insight using a model of TBI in rats. Our data indicates that lung infection did not spontaneously develop during acute and sub-acute stages post-LFPI in adult male rats. Our finding is consistent with previous studies that found that both a
Funding
This study was funded by grants and fellowship to SRS from the National Health and Medical Research Council. PMCE was funded by ECR Fellowship from National Health and Medical Research Council.
Declaration of Competing Interest
The authors declare no conflict of interest.
Acknowledgements
We acknowledge that the graphical abstract was created with BioRender.com.
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