Mild Traumatic Brain Injury Attenuates Pneumonia-Induced Lung Injury by Modulations of Alveolar Macrophage Bactericidal Activity and M1 Polarization

Abstract

Traumatic brain injury is one of the main causes of death and disability worldwide, and results in multisystem complications. However, the mechanism of mild traumatic brain injury (MTBI) on lung injury remains unclear. In this study, we used a murine model of MTBI and pneumonia (Pseudomonas aeruginosa;) to explore the relationship between these conditions and the underlying mechanism. Methods: Mice (n = 104) were divided into control, MTBI, pneumonia, and MTBI + pneumonia groups. MTBI was induced by the weight-drop method. Pneumonia was induced by intratracheal injection with P. aeruginosa Xen5 strain. Animals were killed 24 h after bacterial challenging. Histological, cellular, and molecular indices of brain and lung injury were assessed using various methods. Results: Mice in both the MTBI and pneumonia groups had more Fluoro-Jade C-positive neurons than did the controls (P < 0.01), but mice in the MTBI + pneumonia group had fewer Fluoro-Jade C-positive cells than did the pneumonia group (P < 0.01). The MTBI + pneumonia mice showed decreased bacterial load (P < 0.05), reduced lung injury score and pulmonary permeability (P < 0.01), less inflammatory cells, and lower levels of proinflammatory cytokines (TNF-α and IL-1β; P < 0.01) when compared with the pneumonia group. Molecular analysis indicated lower levels of phosphorylated nuclear factor-κB in the lung of MTBI + pneumonia mice compared with the pneumonia group (P < 0.01). Furthermore, alveolar macrophages from MTBI mice exhibited enhanced bactericidal capacity compared with those from controls (P < 0.01). Moreover, MTBI + pneumonia mice exhibited less CD86-positive M1 macrophages compared with the pneumonia group (P < 0.01). Conclusions: MTBI attenuates pneumonia-induced acute lung injury through the modulation of alveolar macrophage bactericidal capacity and M1 polarization in bacterial pneumonia model.

Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury

“…With an increasing awareness of brainlung interactions and the potential for an altered immune response as a consequence of brain injury [as reviewed elsewhere; e.g., 70], we had hypothesized that TBI alone may influence lung immune responses. For example, in models of lung infections with Pseudomonas aeruginosa, some studies have observed reduced bacterial clearance in animals that had previously sustained a TBI [32], while others have seen a reduced bacterial burden (presumably increased bacterial clearance) in TBI mice post-infection [71][72][73]. However, this was not the case in our model.…”

“…While experimental paradigms of combined TBI and live infection models are rare, studies incorporating post-TBI infection with Citrobacter rodentium, Pseudomonas aeruginosa, or Streptococcus pneumoniae have all reported that the dual insult worsens neuroinflammation and mortality [32,33,38]. Of note, these studies all incorporated a moderate or severe TBI model, whereas other studies have suggested that mild TBI may conversely be protective against P. aeruginosa pneumonia [71,72]. A more complete understanding of combined neurotrauma and infection insults is necessary to ensure that model systems can generate data of clinical relevance [31].…”

The Central Fluid Percussion Brain Injury in a Gyrencephalic Pig Brain: Scalable Diffuse Injury and Tissue Viability for Glial Cell Immunolabeling following Long-Term Refrigerated Storage

“…Studies have recently shown that brain injury can induce changes within systemic organs systems, including both the kidney and lung, both regions involved in regulating the HCO3, pH, and PaO2 of the blood. Kidney and lung pathology has been shown to occur in rodent models of mild TBI [ 69 , 70 , 71 , 72 , 73 ]. Retrospective clinical studies also found that either acute kidney injury [ 74 ] or acute lung injury [ 75 ] were associated with worse outcomes in TBI patients, indicating that systemic organ changes could be occurring in the human population as well.…”