The NLRP3 Inflammasome: An Important Driver of Neuroinflammation in Hemorrhagic Stroke

Yang, Shengchun; Shao, Gaofeng; Chen, Jiangli; Gong, Jie

doi:10.1007/s10571-017-0526-9

Cited by 50 publications

(25 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…44,46 The inflammasome acts as the master-regulator of IL-1b and facilitates the innate immune response after CNS injury. 26,[56][57][58] Our results show increased levels of NLRP3 inflammasome proteins (NLRP3, caspase-1, and ASC) acutely after injury, indicating that activation of the NLRP3 inflammasome plays a significant role inducing the innate immune response after PTBI. In addition to NLRP3, other inflammasomes such as the NLRP1 also may activate after injury.…”

mentioning

confidence: 58%

Microglial Inflammasome Activation in Penetrating Ballistic-Like Brain Injury

Lee

Gajavelli

Spurlock

et al. 2018

Journal of Neurotrauma

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 58%

Microglial Inflammasome Activation in Penetrating Ballistic-Like Brain Injury

Lee

Gajavelli

Spurlock

et al. 2018

Journal of Neurotrauma

View full text Add to dashboard Cite

show abstract

“…In addition, inflammasomes are sensitive to stimulations by internal disturbance, such as misfolded or aggregated proteins and aberrant products of energy metabolism, broadening the range of inflammation inducers beyond infectious stimuli ( 90 ). In ischemic or hemorrhagic stroke models, expression of the NLRP3, a known microglial inflammasome ( 91 , 92 ) component, was increased, and specific blockade of NLRP3 reduced stroke induced neural damage and functional deficits ( 93 , 94 ). Several NLRP3 component proteins were also induced in the pathological tissues in Alzheimer’s disease ( 95 ).…”

Section: The Promises and Limitations Of The Inflammatory Paradigmmentioning

confidence: 99%

Microglia and CNS Interleukin-1: Beyond Immunological Concepts

2018

View full text Add to dashboard Cite

Activation of microglia and expression of the inflammatory cytokine interleukin-1 (IL-1) in the CNS have become almost synonymous with neuroinflammation. In numerous studies, increased CNS IL-1 expression and altered microglial morphology have been used as hallmarks of CNS inflammation. A central concept of how CNS IL-1 and microglia influence functions of the nervous system was derived from the notion initially generated in the peripheral immune system: IL-1 stimulates monocyte/macrophage (the peripheral counterparts of microglia) to amplify inflammation. It is increasingly clear, however, CNS IL-1 acts on other targets in the CNS and microglia participates in many neural functions that are not related to immunological activities. Further, CNS exhibits immunological privilege (although not as absolute as previously thought), rendering amplification of inflammation within CNS under stringent control. This review will analyze current literature to evaluate the contribution of immunological and non-immunological aspects of microglia/IL-1 interaction in the CNS to gain insights for how these aspects might affect health and disease in the nervous tissue.

show abstract

“…Previous research has indicated that high levels of ROS under multiple kinds of cellular stress, particularly those produced by mitochondria (mtROS), activates the NLRP3 inflammasome signal pathway (71)(72)(73)(74). In detail, high levels of ROS induce the ROS scavenging protein thioredoxin resolving from thioredoxin interacting/inhibiting protein (TXNIP), which then directly binds with NLRP3 proteins and modulates its assembly via oligomerization (75)(76)(77). Although several investigations have demonstrated that TXNIP is necessary for NLRP3 inflammasome assembly, a cell type-specific modulation of TXNIP occurs, which limits its mediation of inflammatory response ROS signaling pathway activation to particular cell types (78)(79)(80).…”

Section: Activation Of the Nlrp3 Inflammasome Pathway In Ischemic Strokementioning

confidence: 99%