VX765 Attenuates Pyroptosis and HMGB1TLR4NF-κB Pathways to Improve Functional Outcomes in TBI Mice
Joint Authors
ZhuGe, Qichuan
Shen, Jie
Huang, Lijie
Nyanzu, Mark
Wang, Kankai
Zhu, Xiaohong
Yu, Enxing
Sun, Zhezhe
Yang, Su
Ru, Junnan
Zhang, Hengli
Wang, Zhenzhong
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-21, 21 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-04-15
Country of Publication
Egypt
No. of Pages
21
Main Subjects
Abstract EN
Background.
Traumatic brain injury (TBI) refers to temporary or permanent damage to brain function caused by penetrating objects or blunt force trauma.
TBI activates inflammasome-mediated pathways and other cell death pathways to remove inactive and damaged cells, however, they are also harmful to the central nervous system.
The newly discovered cell death pattern termed pyroptosis has become an area of interest.
It mainly relies on caspase-1-mediated pathways, leading to cell death.
Methods.
Our research focus is VX765, a known caspase-1 inhibitor which may offer neuroprotection after the process of TBI.
We established a controlled cortical impact (CCI) mouse model and then controlled the degree of pyroptosis in TBI with VX765.
The effects of caspase-1 inhibition on inflammatory response, pyroptosis, blood-brain barrier (BBB), apoptosis, and microglia activation, in addition to neurological deficits, were investigated.
Results.
We found that TBI led to NOD-like receptors (NLRs) as well as absent in melanoma 2 (AIM2) inflammasome-mediated pyroptosis in the damaged cerebral cortex.
VX765 curbed the expressions of indispensable inflammatory subunits (caspase-1 as well as key downstream proinflammatory cytokines such as interleukin- (IL-) 1β and IL-18).
It also inhibited gasdermin D (GSDMD) cleavage and apoptosis-associated spot-like protein (ASC) oligomerization in the injured cortex.
In addition to the above, VX765 also inhibited the inflammatory activity of the high-mobility cassette -1/Toll-like receptor 4/nuclear factor-kappa B (HMGB1/TLR4/NF-kappa B) pathway.
By inhibiting pyroptosis and inflammatory mediator expression, we demonstrated that VX765 can decrease blood-brain barrier (BBB) leakage, apoptosis, and microglia polarization to exhibit its neuroprotective effects.
Conclusion.
In conclusion, VX765 can counteract neurological damage after TBI by reducing pyroptosis and HMGB1/TLR4/NF-κB pathway activities.
VX765 may have a good therapeutic effect on TBI.
American Psychological Association (APA)
Sun, Zhezhe& Nyanzu, Mark& Yang, Su& Zhu, Xiaohong& Wang, Kankai& Ru, Junnan…[et al.]. 2020. VX765 Attenuates Pyroptosis and HMGB1TLR4NF-κB Pathways to Improve Functional Outcomes in TBI Mice. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-21.
https://search.emarefa.net/detail/BIM-1205449
Modern Language Association (MLA)
Sun, Zhezhe…[et al.]. VX765 Attenuates Pyroptosis and HMGB1TLR4NF-κB Pathways to Improve Functional Outcomes in TBI Mice. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-21.
https://search.emarefa.net/detail/BIM-1205449
American Medical Association (AMA)
Sun, Zhezhe& Nyanzu, Mark& Yang, Su& Zhu, Xiaohong& Wang, Kankai& Ru, Junnan…[et al.]. VX765 Attenuates Pyroptosis and HMGB1TLR4NF-κB Pathways to Improve Functional Outcomes in TBI Mice. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-21.
https://search.emarefa.net/detail/BIM-1205449
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205449