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Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our resul...

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Autores principales: Wu, Xun, Cui, Wenxing, Guo, Wei, Liu, Haixiao, Luo, Jianing, Zhao, Lei, Guo, Hao, Zheng, Longlong, Bai, Hao, Feng, Dayun, Qu, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532238/
https://www.ncbi.nlm.nih.gov/pubmed/32436179
http://dx.doi.org/10.1007/s12264-020-00505-7
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author Wu, Xun
Cui, Wenxing
Guo, Wei
Liu, Haixiao
Luo, Jianing
Zhao, Lei
Guo, Hao
Zheng, Longlong
Bai, Hao
Feng, Dayun
Qu, Yan
author_facet Wu, Xun
Cui, Wenxing
Guo, Wei
Liu, Haixiao
Luo, Jianing
Zhao, Lei
Guo, Hao
Zheng, Longlong
Bai, Hao
Feng, Dayun
Qu, Yan
author_sort Wu, Xun
collection PubMed
description Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-020-00505-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-75322382020-10-19 Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice Wu, Xun Cui, Wenxing Guo, Wei Liu, Haixiao Luo, Jianing Zhao, Lei Guo, Hao Zheng, Longlong Bai, Hao Feng, Dayun Qu, Yan Neurosci Bull Original Article Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-020-00505-7) contains supplementary material, which is available to authorized users. Springer Singapore 2020-05-21 /pmc/articles/PMC7532238/ /pubmed/32436179 http://dx.doi.org/10.1007/s12264-020-00505-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Article
Wu, Xun
Cui, Wenxing
Guo, Wei
Liu, Haixiao
Luo, Jianing
Zhao, Lei
Guo, Hao
Zheng, Longlong
Bai, Hao
Feng, Dayun
Qu, Yan
Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice
title Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice
title_full Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice
title_fullStr Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice
title_full_unstemmed Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice
title_short Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice
title_sort acrolein aggravates secondary brain injury after intracerebral hemorrhage through drp1-mediated mitochondrial oxidative damage in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532238/
https://www.ncbi.nlm.nih.gov/pubmed/32436179
http://dx.doi.org/10.1007/s12264-020-00505-7
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