Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury

Background: Spinal cord injury (SCI), a major public health problem, has no effective treatment. A large number of studies have confirmed that histone deacetylases (HDACs) are involved in the physiologic processes that occur following SCI. We tried to uncover the potential neuroprotective role of en...

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Autores principales:	Chen Dai, Bin Liu, Bibo Peng, Bo Qu, Jiezhi Lin, Baogan Peng, Duan-Ming Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	SCI entinostat HDAC NLRP3 inflammasome neuronal damage Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/dff94cc96e6f42d79a6a797d20fba87f
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spelling	oai:doaj.org-article:dff94cc96e6f42d79a6a797d20fba87f2021-12-01T06:58:37ZEntinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury1663-981210.3389/fphar.2021.774539https://doaj.org/article/dff94cc96e6f42d79a6a797d20fba87f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.774539/fullhttps://doaj.org/toc/1663-9812Background: Spinal cord injury (SCI), a major public health problem, has no effective treatment. A large number of studies have confirmed that histone deacetylases (HDACs) are involved in the physiologic processes that occur following SCI. We tried to uncover the potential neuroprotective role of entinostat (a class I HDAC inhibitor) in SCI.Methods: We conducted a study on a preclinical mouse model of SCI and OGD-induced neuronal damage to present the role of entinostat by the analysis of motor function, histopathologic damage, local NLRP3 inflammasome activation, and neuronal damage.Results: The results showed that entinostat suppressed HDAC activation (including HDAC1 and HDAC3 expression), improved the grip strength and BMS score, spinal edema, cell death, and local NLRP3 inflammasome activation in the spinal cord following SCI. Furthermore, entinostat significantly increased OGD-inhibited neuronal activity and decreased PI-positive cells, HDAC activation, caspase-1 activation, IL-1β and IL-18 levels, and NLRP3 expression.Conclusion: In summary, we first documented that entinostat improved the motor function, histopathologic damage, and local inflammatory response and NLRP3 inflammasome activation in the spinal cord following SCI and also presented the neuroprotective role of OGD-induced neuronal damage via the NLRP3 inflammasome. Thus, our study has the potential to reveal the interaction between the HDAC and NLRP3 inflammasome in the pathologic process as well as SCI and further promote the clinical indications of HDACi entinostat and clinical treatment for the inflammatory response after SCI.Chen DaiChen DaiBin LiuBibo PengBo QuJiezhi LinBaogan PengDuan-Ming LiFrontiers Media S.A.articleSCIentinostatHDACNLRP3 inflammasomeneuronal damageTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SCI entinostat HDAC NLRP3 inflammasome neuronal damage Therapeutics. Pharmacology RM1-950
spellingShingle	SCI entinostat HDAC NLRP3 inflammasome neuronal damage Therapeutics. Pharmacology RM1-950 Chen Dai Chen Dai Bin Liu Bibo Peng Bo Qu Jiezhi Lin Baogan Peng Duan-Ming Li Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury
description	Background: Spinal cord injury (SCI), a major public health problem, has no effective treatment. A large number of studies have confirmed that histone deacetylases (HDACs) are involved in the physiologic processes that occur following SCI. We tried to uncover the potential neuroprotective role of entinostat (a class I HDAC inhibitor) in SCI.Methods: We conducted a study on a preclinical mouse model of SCI and OGD-induced neuronal damage to present the role of entinostat by the analysis of motor function, histopathologic damage, local NLRP3 inflammasome activation, and neuronal damage.Results: The results showed that entinostat suppressed HDAC activation (including HDAC1 and HDAC3 expression), improved the grip strength and BMS score, spinal edema, cell death, and local NLRP3 inflammasome activation in the spinal cord following SCI. Furthermore, entinostat significantly increased OGD-inhibited neuronal activity and decreased PI-positive cells, HDAC activation, caspase-1 activation, IL-1β and IL-18 levels, and NLRP3 expression.Conclusion: In summary, we first documented that entinostat improved the motor function, histopathologic damage, and local inflammatory response and NLRP3 inflammasome activation in the spinal cord following SCI and also presented the neuroprotective role of OGD-induced neuronal damage via the NLRP3 inflammasome. Thus, our study has the potential to reveal the interaction between the HDAC and NLRP3 inflammasome in the pathologic process as well as SCI and further promote the clinical indications of HDACi entinostat and clinical treatment for the inflammatory response after SCI.
format	article
author	Chen Dai Chen Dai Bin Liu Bibo Peng Bo Qu Jiezhi Lin Baogan Peng Duan-Ming Li
author_facet	Chen Dai Chen Dai Bin Liu Bibo Peng Bo Qu Jiezhi Lin Baogan Peng Duan-Ming Li
author_sort	Chen Dai
title	Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury
title_short	Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury
title_full	Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury
title_fullStr	Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury
title_full_unstemmed	Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury
title_sort	entinostat improves motor function and neuronal damage via downregulating nlrp3 inflammasome activation after spinal cord injury
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/dff94cc96e6f42d79a6a797d20fba87f
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Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury

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