Neural-respiratory inflammasome axis in traumatic brain injury

Exp Neurol. 2020 Jan:323:113080. doi: 10.1016/j.expneurol.2019.113080. Epub 2019 Oct 15.

Abstract

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality. Approximately 20-25% of TBI subjects develop Acute Lung Injury (ALI), but the pathomechanisms of TBI-induced ALI remain poorly defined. Currently, mechanical ventilation is the only therapeutic intervention for TBI-induced lung injury. Our recent studies have shown that the inflammasome plays an important role in the systemic inflammatory response leading to lung injury-post TBI. Here, we outline the role of the extracellular vesicle (EV)-mediated inflammasome signaling in the etiology of TBI-induced ALI. Furthermore, we evaluate the efficacy of a low molecular weight heparin (Enoxaparin, a blocker of EV uptake) and a monoclonal antibody against apoptosis speck-like staining protein containing a caspase recruitment domain (anti-ASC) as therapeutics for TBI-induced lung injury. We demonstate that activation of an EV-mediated Neural-Respiratory Inflammasome Axis plays an essential role in TBI-induced lung injury and disruption of this axis has therapeutic potential as a treatment strategy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acute Lung Injury / etiology*
  • Acute Lung Injury / immunology*
  • Acute Lung Injury / physiopathology
  • Animals
  • Brain Injuries, Traumatic / complications*
  • Brain Injuries, Traumatic / immunology*
  • Brain Injuries, Traumatic / physiopathology
  • Extracellular Vesicles / immunology
  • Humans
  • Inflammasomes / immunology*
  • Inflammation / etiology
  • Inflammation / immunology
  • Inflammation / physiopathology

Substances

  • Inflammasomes