Neuron-autonomous transcriptome changes upon ischemia/reperfusion injury

Abstract Ischemic stroke and the following reperfusion, an acute therapeutic intervention, can cause irreversible brain damages. However, the underlying pathological mechanisms are still under investigation. To obtain a comprehensive, real-time view of the cell-autonomous mechanisms involved in isch...

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Autores principales:	Jinlong Shi, Xia Chen, Haiying Li, Youjia Wu, Shouyan Wang, Wei Shi, Jian Chen, Yaohui Ni
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/90d19e4c69ed4739840859edc49597bc
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spelling	oai:doaj.org-article:90d19e4c69ed4739840859edc49597bc2021-12-02T15:06:15ZNeuron-autonomous transcriptome changes upon ischemia/reperfusion injury10.1038/s41598-017-05342-92045-2322https://doaj.org/article/90d19e4c69ed4739840859edc49597bc2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05342-9https://doaj.org/toc/2045-2322Abstract Ischemic stroke and the following reperfusion, an acute therapeutic intervention, can cause irreversible brain damages. However, the underlying pathological mechanisms are still under investigation. To obtain a comprehensive, real-time view of the cell-autonomous mechanisms involved in ischemic stroke and reperfusion, we applied the next-generation sequencing (NGS) technology to characterize the temporal changes in gene expression profiles using primarily cultured hippocampal neurons under an oxygen-glucose deprivation/reperfusion (OGD/R) condition. We first identified the differentially expressed genes (DEGs) between normal cultured neurons, neurons with OGD, and neurons with OGD followed by reperfusion for 6 h, 12 h, and 18 h, respectively. We then performed bioinformatics analyses, including gene ontological (GO) and pathway analysis and co-expression network analysis to screen for novel key pathways and genes involved in the pathology of OGD/R. After we confirmed the changes of selected key genes in hippocampal cultures with OGD/R, we further validated their expression changes in an in vivo ischemic stroke model (MCAO). Finally, we demonstrated that prevention of the up-regulation of a key gene (Itga5) associated with OGD/R promoted hippocampal neuronal survival. Our research thereby provided novel insights into the molecular mechanisms in ischemic stroke pathophysiology and potential targets for therapeutic intervention after ischemic stroke.Jinlong ShiXia ChenHaiying LiYoujia WuShouyan WangWei ShiJian ChenYaohui NiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jinlong Shi Xia Chen Haiying Li Youjia Wu Shouyan Wang Wei Shi Jian Chen Yaohui Ni Neuron-autonomous transcriptome changes upon ischemia/reperfusion injury
description	Abstract Ischemic stroke and the following reperfusion, an acute therapeutic intervention, can cause irreversible brain damages. However, the underlying pathological mechanisms are still under investigation. To obtain a comprehensive, real-time view of the cell-autonomous mechanisms involved in ischemic stroke and reperfusion, we applied the next-generation sequencing (NGS) technology to characterize the temporal changes in gene expression profiles using primarily cultured hippocampal neurons under an oxygen-glucose deprivation/reperfusion (OGD/R) condition. We first identified the differentially expressed genes (DEGs) between normal cultured neurons, neurons with OGD, and neurons with OGD followed by reperfusion for 6 h, 12 h, and 18 h, respectively. We then performed bioinformatics analyses, including gene ontological (GO) and pathway analysis and co-expression network analysis to screen for novel key pathways and genes involved in the pathology of OGD/R. After we confirmed the changes of selected key genes in hippocampal cultures with OGD/R, we further validated their expression changes in an in vivo ischemic stroke model (MCAO). Finally, we demonstrated that prevention of the up-regulation of a key gene (Itga5) associated with OGD/R promoted hippocampal neuronal survival. Our research thereby provided novel insights into the molecular mechanisms in ischemic stroke pathophysiology and potential targets for therapeutic intervention after ischemic stroke.
format	article
author	Jinlong Shi Xia Chen Haiying Li Youjia Wu Shouyan Wang Wei Shi Jian Chen Yaohui Ni
author_facet	Jinlong Shi Xia Chen Haiying Li Youjia Wu Shouyan Wang Wei Shi Jian Chen Yaohui Ni
author_sort	Jinlong Shi
title	Neuron-autonomous transcriptome changes upon ischemia/reperfusion injury
title_short	Neuron-autonomous transcriptome changes upon ischemia/reperfusion injury
title_full	Neuron-autonomous transcriptome changes upon ischemia/reperfusion injury
title_fullStr	Neuron-autonomous transcriptome changes upon ischemia/reperfusion injury
title_full_unstemmed	Neuron-autonomous transcriptome changes upon ischemia/reperfusion injury
title_sort	neuron-autonomous transcriptome changes upon ischemia/reperfusion injury
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/90d19e4c69ed4739840859edc49597bc
work_keys_str_mv	AT jinlongshi neuronautonomoustranscriptomechangesuponischemiareperfusioninjury AT xiachen neuronautonomoustranscriptomechangesuponischemiareperfusioninjury AT haiyingli neuronautonomoustranscriptomechangesuponischemiareperfusioninjury AT youjiawu neuronautonomoustranscriptomechangesuponischemiareperfusioninjury AT shouyanwang neuronautonomoustranscriptomechangesuponischemiareperfusioninjury AT weishi neuronautonomoustranscriptomechangesuponischemiareperfusioninjury AT jianchen neuronautonomoustranscriptomechangesuponischemiareperfusioninjury AT yaohuini neuronautonomoustranscriptomechangesuponischemiareperfusioninjury
_version_	1718388528808722432

Neuron-autonomous transcriptome changes upon ischemia/reperfusion injury

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