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AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage....

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Autores principales: Lin, Xiao, Ye, Haotuo, Siaw-Debrah, Felix, Pan, Sishi, He, Zibin, Ni, Haoqi, Xu, Zhu, Jin, Kunlin, Zhuge, Qichuan, Huang, Lijie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206581/
https://www.ncbi.nlm.nih.gov/pubmed/30410928
http://dx.doi.org/10.1155/2018/3706047
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author Lin, Xiao
Ye, Haotuo
Siaw-Debrah, Felix
Pan, Sishi
He, Zibin
Ni, Haoqi
Xu, Zhu
Jin, Kunlin
Zhuge, Qichuan
Huang, Lijie
author_facet Lin, Xiao
Ye, Haotuo
Siaw-Debrah, Felix
Pan, Sishi
He, Zibin
Ni, Haoqi
Xu, Zhu
Jin, Kunlin
Zhuge, Qichuan
Huang, Lijie
author_sort Lin, Xiao
collection PubMed
description Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage. Pyroptosis is a newly discovered cell death pathway that has gained attention in recent years. This pathway mainly depends on activation of caspase-1-mediated cascades to cause cell death. We tested a well-known selective inhibitor of caspase-1, AC-YVAD-CMK, which has previously been found to have neuroprotective effects in ICH mice model, to ascertain its effects on the activation of inflammasomes mediated pyroptosis. Our results showed that AC-YVAD-CMK could reduce caspase-1 activation and inhibit IL-1β production and maturation, but has no effect on NLRP3 expression, an upstream inflammatory complex. AC-YVAD-CMK administration also resulted in reduction in M1-type microglia polarization around the hematoma, while increasing the number of M2-type cells. Furthermore, AC-YVAD-CMK treated mice showed some recovery of neurological function after hemorrhage especially at the hyperacute and subacute stage resulting in some degree of limb movement. In conclusion, we are of the view that AC-YVAD-CMK could inhibit pyroptosis, decrease the secretion or activation of inflammatory factors, and affect the polarization of microglia resulting in improvement of neurological function after ICH.
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spelling pubmed-62065812018-11-08 AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage Lin, Xiao Ye, Haotuo Siaw-Debrah, Felix Pan, Sishi He, Zibin Ni, Haoqi Xu, Zhu Jin, Kunlin Zhuge, Qichuan Huang, Lijie Biomed Res Int Research Article Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage. Pyroptosis is a newly discovered cell death pathway that has gained attention in recent years. This pathway mainly depends on activation of caspase-1-mediated cascades to cause cell death. We tested a well-known selective inhibitor of caspase-1, AC-YVAD-CMK, which has previously been found to have neuroprotective effects in ICH mice model, to ascertain its effects on the activation of inflammasomes mediated pyroptosis. Our results showed that AC-YVAD-CMK could reduce caspase-1 activation and inhibit IL-1β production and maturation, but has no effect on NLRP3 expression, an upstream inflammatory complex. AC-YVAD-CMK administration also resulted in reduction in M1-type microglia polarization around the hematoma, while increasing the number of M2-type cells. Furthermore, AC-YVAD-CMK treated mice showed some recovery of neurological function after hemorrhage especially at the hyperacute and subacute stage resulting in some degree of limb movement. In conclusion, we are of the view that AC-YVAD-CMK could inhibit pyroptosis, decrease the secretion or activation of inflammatory factors, and affect the polarization of microglia resulting in improvement of neurological function after ICH. Hindawi 2018-10-16 /pmc/articles/PMC6206581/ /pubmed/30410928 http://dx.doi.org/10.1155/2018/3706047 Text en Copyright © 2018 Xiao Lin et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lin, Xiao
Ye, Haotuo
Siaw-Debrah, Felix
Pan, Sishi
He, Zibin
Ni, Haoqi
Xu, Zhu
Jin, Kunlin
Zhuge, Qichuan
Huang, Lijie
AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage
title AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage
title_full AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage
title_fullStr AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage
title_full_unstemmed AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage
title_short AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage
title_sort ac-yvad-cmk inhibits pyroptosis and improves functional outcome after intracerebral hemorrhage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206581/
https://www.ncbi.nlm.nih.gov/pubmed/30410928
http://dx.doi.org/10.1155/2018/3706047
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