VX765 Attenuates Pyroptosis and HMGB1TLR4NF-κB Pathways to Improve Functional Outcomes in TBI Mice
المؤلفون المشاركون
ZhuGe, Qichuan
Shen, Jie
Huang, Lijie
Nyanzu, Mark
Wang, Kankai
Zhu, Xiaohong
Yu, Enxing
Sun, Zhezhe
Yang, Su
Ru, Junnan
Zhang, Hengli
Wang, Zhenzhong
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2020، العدد 2020 (31 ديسمبر/كانون الأول 2020)، ص ص. 1-21، 21ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2020-04-15
دولة النشر
مصر
عدد الصفحات
21
التخصصات الرئيسية
الملخص 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.
نمط استشهاد جمعية علماء النفس الأمريكية (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
نمط استشهاد الجمعية الأمريكية للغات الحديثة (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
نمط استشهاد الجمعية الطبية الأمريكية (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
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1205449
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر