Abstract

Mild traumatic brain injury in the form of concussion is extremely common, and the potential effects on pulmonary priming have been underestimated. The aim of this study was to characterize the pulmonary response following mild traumatic brain injury and assess the pulmonary susceptibility to lung injury after a subsequent innocuous pulmonary insult. Experimental in vivo study. University research laboratory. Male CD1 mice. We developed a model of concussive traumatic brain injury in mice followed by pulmonary acid microaspiration. To assess the dependent role of neutrophils in mediating pulmonary injury, we specifically depleted neutrophils. Lateral fluid percussion to the brain resulted in neuronal damage and neutrophil infiltration as well as extensive pulmonary interstitial neutrophil accumulation but no alveolar injury. Following subsequent innocuous acid microaspiration, augmented alveolar neutrophil influx led to the development of pulmonary hemorrhage that was reduced following neutrophil depletion. This model shows for the first time that innocuous acid microaspiration is sufficient to induce neutrophil-mediated lung injury following mild concussion and that the extracranial effects of mild traumatic brain injury have been underestimated.

Highlights

  • We show for the first time that mild traumatic brain injury (TBI) induces massive pulmonary sequestration of interstitial neutrophils that transmigrate into the alveolar compartment following a subsequent small inflammatory insult such as acid aspiration to induce injury

  • Sham and fluid percussion injury (FPI) were significantly different in righting times, indicating that a significant cortical impact had occurred (Supplementary Fig. E2, Supplemental Digital Content 3, http://links.lww.com/CCM/ D742; legend, Supplemental Digital Content 1, http://links.lww. com/CCM/D740)

  • Significant neuronal damage, evident by the appearance of triangularly shaped, Mild Fluid Percussion Cortical Injury Induces Massive Pulmonary Interstitial Neutrophil Migration Without Pulmonary Vascular Leak Lungs from FPI and sham animals were assessed for evidence of inflammation

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Summary

Objectives

Mild traumatic brain injury in the form of concussion is extremely common, and the potential effects on pulmonary priming have been underestimated. The aim of this study was to characterize the pulmonary response following mild traumatic brain injury and assess the pulmonary susceptibility to lung injury after a subsequent innocuous pulmonary insult. Drs Andrews, Rhodes, and Dhaliwal conceived the project. Drs Humphries, Rhodes, and Dhaliwal designed the experiments. Dr Humphries, Dr O’Neill, and Ms Scholefield performed experiments. Drs Mackinnon, Rossi, Haslett, Andrews, and Rhodes provided guidance and edited the article. Drs Humphries and Dhaliwal wrote the article

Methods
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