Traumatic brain injury-induced acute lung injury: Evidence for activation and inhibition of a neural-respiratory-inflammasome axis

Nadine A. Kerr, Juan Pablo P de Rivero Vaccari, Sam Abbassi, Harmanpreet Kaur, Ronald Zambrano, Shu Wu, W. Dalton Dietrich, Robert Keane

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2067-2076
Number of pages10
JournalJournal of Neurotrauma
Volume35
Issue number17
DOIs
StatePublished - Sep 1 2018

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Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology

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