Citation

Lee SW, Gajavelli S, Spurlock MS, Andreoni C, de Rivero Vaccari JP, Bullock MR, Keane RW, Dietrich WD. J. Neurotrauma 2018; 35(14): 1681-1693.

Affiliation

University of Miami, Neurological Surgery , 1095 NW 14 Ter (R48) , Miami, Florida, United States , 33136 ; ddietrich@miami.edu.

Copyright

(Copyright © 2018, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2017.5530

PMID

29439605

Abstract

Penetrating traumatic brain injury (PTBI) is a significant cause of death and disability in the United States. Inflammasomes are one of the key regulators of the interleukin (IL)-1β mediated inflammatory responses after traumatic brain injury (TBI). However, the contribution of inflammasome signaling after PTBI has not been determined. In this study, adult male Sprague-Dawley rats were subjected to sham procedures or penetrating ballistic-like brain injury (PBBI) and sacrificed at various time points. Tissues were assessed by immunoblot analysis for expression of IL-1β, IL-18 and components of the inflammasome: apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, X-linked inhibitor of apoptosis protein (XIAP), NOD-like receptor protein 3 (NLRP3), and gasdermin-D (GSDMD). Specific cell types expressing inflammasome proteins were also evaluated immunohistochemically and assessed quantitatively. After PBBI, expression of IL-1β, IL-18, caspase-1, ASC, XIAP, and NLRP3 peaked around 48h. Brain protein lysates from PTBI animals showed pyroptosome formation evidenced by ASC laddering, and also contained increased expression of GSDMD at 48h after injury. ASC-positive immunoreactive neurons within the perilesional cortex were observed at 24 hrs. At 48hrs, ASC expression was concentrated in morphologically activated cortical microglia. This expression of ASC in activated microglia persisted until 12 weeks following PBBI. This is the first report of inflammasome activation after PBBI. Our results demonstrate cell-specific patterns of inflammasome activation and pyroptosis predominantly in microglia suggesting a sustained pro-inflammatory state following PBBI, thus offering a therapeutic target for this type of brain injury.

Language: en

Keywords

INFLAMMATION; Penetrating Ballistic-like Brain Injury; TRAUMATIC BRAIN INJURY