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J Neurotrauma. 2018 Sep 1;35(17):2067-2076. doi: 10.1089/neu.2017.5430. Epub 2018 Jun 8.

Traumatic Brain Injury-Induced Acute Lung Injury: Evidence for Activation and Inhibition of a Neural-Respiratory-Inflammasome Axis.

Author information

1
1 Department of Neurological Surgery, University of Miami Miller School of Medicine , Miami, Florida.
2
2 Department of Physiology and Biophysics, University of Miami Miller School of Medicine , Miami, Florida.
3
3 Department of Pediatrics, University of Miami Miller School of Medicine , Miami, Florida.

Abstract

Approximately 20-25% of traumatic brain injury (TBI) subjects develop acute lung injury (ALI), but the pathomechanisms of TBI-induced ALI remain poorly defined. Our previous work has shown that the inflammasome plays a critical role in TBI-induced secondary pathophysiology and that inflammasome proteins are released in extracellular vesicles (EV) after TBI. Here we investigated whether EV-mediated inflammasome signaling contributed to the etiology of TBI-induced ALI. C57/BL6 male mice were subjected to controlled cortical impact (CCI), and the brains and lungs were examined for inflammasome activation and ALI at 4 and 24 h after TBI. We show that TBI releases EV containing inflammasome proteins into serum that target the lung to cause ALI, supporting activation of a neural-respiratory-inflammasome axis. Administration of a low-molecular-weight heparin (enoxaparin, a blocker of EV uptake) or treatment with a monoclonal antibody against apoptosis speck-like staining protein containing a caspase recruitment domain (anti-ASC) after adoptive transfer of EV isolated from TBI-injured mice significantly inhibited inflammasome activation in the lungs of recipient mice resulting in improved ALI scores.This axis constitutes an important arm of the innate inflammatory response in lung pathology after TBI and targeting this axis represents a novel therapeutic treatment for TBI-induced ALI.

KEYWORDS:

acute lung injury; extracellular vesicles; inflammasome; innate immune response; traumatic brain injury

PMID:
29648974
PMCID:
PMC6098413
[Available on 2019-09-01]
DOI:
10.1089/neu.2017.5430

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