To evaluate the use of inflammasome signaling proteins, specifically ASC, in serum as a prognostic tool in pediatric traumatic brain injury (pTBI). 

pTBI is a major cause of death and disability in children. Following a TBI, injured tissue releases damaged-associated molecular pattern molecules (DAMPs), which leads to activation of the innate immune response. These DAMPs are regulated by the inflammasome. The NLRP3 inflammasome signaling proteins (ASC, caspase-1, IL-18) have been evaluated as potential neuro-biomarkers in adult TBI. However, to this date, none have been reported in the blood of pediatric patients. Here, we report on inflammasome-mediated neuroinflammation in pTBI using blood samples.

Prospective observational cohort study conducted in pediatric intensive care units (ICU) at two academic institutions. 66 pTBI patients (all severities) 0-18 years of age who have had brain imaging studies within 24 hours of injury and 24 healthy controls (HC) were included. Patients with severe psychiatric disorders, pregnant patients, and patients lacking data points were all excluded from the study. TBI severity was assessed with the Glasgow Coma Scale (GCS) at admission. Blood samples were obtained at enrollment, 24 hours, and 48 hours post-injury. A Simple Plex Assay measured inflammasome protein ASC concentration using the Ella System. The Glasgow Outcome Scale Extended for Pediatrics (GOS-E Peds) was used to measure long term outcomes in pTBI at 9-12 months post-injury. Scores were recorded into two binary categories: favorable (GOS-E Peds ≤ 4) and unfavorable (GOS-E Peds > 5).

Serum levels of ASC measured at 0 hours were increased among patients with unfavorable outcomes at 9-12 months post injury (p= 0.04, AUC= 0.7) when compared to TBI patients of the same cohort with favorable outcomes.