Traumatic brain injury in rats induces lung injury and systemic immune suppression.
Traumatic brain injury (TBI) is frequently complicated by acute lung injury, which is predictive for poor outcome. However, it is unclear whether lung injury develops independently or as a result of mechanical ventilation after TBI. Further, TBI is strongly associated with the development of pneumonia, suggesting a specific vulnerability for the development of nosocomial infections in the lung after TBI. In this study, we evaluated whether indeed pulmonary injury and immune suppression develop spontaneously in an animal model of mild TBI (mTBI). TBI was induced in male PVG rats by closed-head trauma using a weight-drop device. Subsequently, we evaluated the effects of this on the lungs as well as on the excitability of the systemic immune system. Finally, we performed an experiment in which TBI was followed by induction of pneumonitis and evaluated whether TBI affects the severity of subsequent pneumonitis induced by intratracheal instillation of heat-killed Staphylococcus aureus. mTBI resulted in significant lung injury, as evidenced by pulmonary edema, protein leakage to the alveolar compartment, and increased concentrations of interleukin-1 and -6 in broncho alveolar lavage fluid (all p<0.05 vs. sham-treated animals). Further, after TBI, the release of tumor necrosis factor alpha was decreased when whole blood was stimulated ex vivo (p<0.05 TBI vs. sham), indicating systemic immune suppression. When TBI was followed by pneumonitis, the severity of subsequent pneumonitis was not different in rats previously subjected to TBI or sham treatment (p>0.05), suggesting that systemic immune suppression is not translated toward the pulmonary compartment in this specific model. We here show that during mild experimental TBI, acute pulmonary injury, as well as a decrease in the excitability of the systemic immune system, can be observed.
1 Department of Neurology, Academic Medical Center , Amsterdam, the Netherlands .
Jan-Dirk
JD
Vermeij
Hamid
H
Aslami
Kees
K
Fluiter
Joris J
JJ
Roelofs
Walter M
WM
van den Bergh
Nicole P
NP
Juffermans
Marcus J
MJ
Schultz
Koen
K
Van der Sluijs
Diederik
D
van de Beek
David J
DJ
van Westerloo
D000818:Animals; D001930:Brain Injuries / Q000150:complications* / Q000276:immunology; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000276:immunology*; D055370:Lung Injury / Q000209:etiology* / Q000276:immunology; D008297:Male; D011014:Pneumonia / Q000209:etiology / Q000276:immunology; D051381:Rats