Back to Search
Start Over
Microglial Inflammasome Activation in Penetrating Ballistic-Like Brain Injury
- Source :
- Journal of Neurotrauma. 35:1681-1693
- Publication Year :
- 2018
- Publisher :
- Mary Ann Liebert Inc, 2018.
-
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. 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), nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3), and gasdermin-D (GSDMD). Specific cell types expressing inflammasome proteins also were evaluated immunohistochemically and assessed quantitatively. After PBBI, expression of IL-1β, IL-18, caspase-1, ASC, XIAP, and NLRP3 peaked around 48 h. Brain protein lysates from PTBI animals showed pyroptosome formation evidenced by ASC laddering, and also contained increased expression of GSDMD at 48 h after injury. ASC-positive immunoreactive neurons within the perilesional cortex were observed at 24 h. At 48 h, 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.
- Subjects :
- Male
0301 basic medicine
Inflammasomes
Traumatic brain injury
Inflammation
Inhibitor of apoptosis
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Brain Injuries, Traumatic
medicine
Animals
Head Injuries, Penetrating
Microglia
Chemistry
Pyroptosis
Interleukin
Inflammasome
Original Articles
medicine.disease
Rats
Cell biology
XIAP
030104 developmental biology
medicine.anatomical_structure
Neurology (clinical)
medicine.symptom
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 15579042 and 08977151
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Journal of Neurotrauma
- Accession number :
- edsair.doi.dedup.....3d4a190e0b4107a3182ac3415a23f409