VX765 Attenuates Pyroptosis and HMGB1/TLR4/NF-kappa B Pathways to Improve Functional Outcomes in TBI Mice

doi:10.1155/2020/7879629

科研成果详情

题名	VX765 Attenuates Pyroptosis and HMGB1/TLR4/NF-kappa B Pathways to Improve Functional Outcomes in TBI Mice
作者	Sun, Zhezhe 1,2; Nyanzu, Mark 1,2; Yang, Su 1,2; Zhu, Xiaohong1,2; Wang, Kankai1,2; Ru, Junnan 1,2; Yu, Enxing 1,2; Zhang, Hengli 1,2; Wang, Zhenzhong 3; Shen, Jie 4; Zhuge, Qichuan1,2; Huang, Lijie1,2
发表日期	2020-04-15
发表期刊	OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Blood Brain Mammals Neurology Central nervous systems Inflammatory activity Inflammatory mediators Inflammatory response Neurological deficit Neuroprotective effects Pro-inflammatory cytokines Traumatic Brain Injuries
其他关键词	TRAUMATIC BRAIN-INJURY ; MICROGLIAL INFLAMMASOME ACTIVATION ; TLR4/NF-KAPPA-B SIGNALING PATHWAY ; SPINAL-CORD-INJURY ; CELL-DEATH ; NLRP3 INFLAMMASOME ; GASDERMIN D ; KAPPA-B ; MOLECULAR-MECHANISMS ; MURINE MODEL
摘要	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-) 1 beta 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-kappa B pathway activities. VX765 may have a good therapeutic effect on TBI.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81771262, 81820108011]; Zhejiang Health Science and Technology Project [2016RCA022]; Ningbo Natural Science Foundation [2018A610310]
出版者	HINDAWI LTD
出版地	LONDON
ISSN	1942-0900
EISSN	1942-0994
卷号	2020 页码:7879629
DOI	10.1155/2020/7879629
页数	21
WOS类目	Cell Biology
WOS研究方向	Cell Biology
WOS记录号	WOS:000530315100002
收录类别	SCIE ; PUBMED ; EI ; SCOPUS
EI入藏号	20202008650316
EI主题词	Cell death
URL	查看原文
PubMed ID	32377306
PMC记录号	PMC7181015
SCOPUSEID	2-s2.0-85084380469
通讯作者地址	[Zhuge, Qichuan]Department of Neurosurgery,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
Scopus学科分类	Biochemistry;Aging;Cell Biology
引用统计	被引频次：37[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/4650
专题	附属第一医院
通讯作者	Zhuge, Qichuan
作者单位	1.Department of Neurosurgery,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 3.Department of Neurosurgery,Yuyao People's Hospital,Ningbo 315000,China; 4.Department of Neurosurgery,First Affiliated Hospital of Medical School of Zhejiang University,Hangzhou 310003 zy91.com,China
第一作者单位	附属第一医院
通讯作者单位	附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Sun, Zhezhe,Nyanzu, Mark,Yang, Su,et al. VX765 Attenuates Pyroptosis and HMGB1/TLR4/NF-kappa B Pathways to Improve Functional Outcomes in TBI Mice[J]. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY,2020,2020:7879629.
APA	Sun, Zhezhe., Nyanzu, Mark., Yang, Su., Zhu, Xiaohong., Wang, Kankai., ... & Huang, Lijie. (2020). VX765 Attenuates Pyroptosis and HMGB1/TLR4/NF-kappa B Pathways to Improve Functional Outcomes in TBI Mice. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2020, 7879629.
MLA	Sun, Zhezhe,et al."VX765 Attenuates Pyroptosis and HMGB1/TLR4/NF-kappa B Pathways to Improve Functional Outcomes in TBI Mice".OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020(2020):7879629.