Neural-respiratory inflammasome axis in traumatic brain injury

• Published in: Experimental neurology Vol. 323; p. 113080
• Main Authors: Kerr, Nadine, de Rivero Vaccari, Juan Pablo, Dietrich, W. Dalton, Keane, Robert W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2020
• Subjects: 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
• ISSN: 0014-4886; 1090-2430; 1090-2430
• DOI: 10.1016/j.expneurol.2019.113080

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.