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.