Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

[INLINE:1] Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site (in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9 (S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that: (1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis; (2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function; (3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and (4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken together, our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis, and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Li Sun [verfasserIn] Zhaoyan Zhao [verfasserIn] Jing Guo [verfasserIn] Yuan Qin [verfasserIn] Qian Yu [verfasserIn] Xiaolong Shi [verfasserIn] Fei Guo [verfasserIn] Haiqin Zhang [verfasserIn] Xude Sun [verfasserIn] Changjun Gao [verfasserIn] Qian Yang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	ischemic stroke; microglia; mitochondria transplantation; neurogenesis; pyroptosis

Übergeordnetes Werk:	In: Neural Regeneration Research - Wolters Kluwer Medknow Publications, 2014, 19(2024), 6, Seite 1325-1335
Übergeordnetes Werk:	volume:19 ; year:2024 ; number:6 ; pages:1325-1335

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.4103/1673-5374.385313

Katalog-ID:	DOAJ095809112

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allfields	10.4103/1673-5374.385313 doi (DE-627)DOAJ095809112 (DE-599)DOAJ6bd9120fb8fc4ab4a20cba8848f9225b DE-627 ger DE-627 rakwb eng RC346-429 Li Sun verfasserin aut Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier [INLINE:1] Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site (in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9 (S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that: (1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis; (2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function; (3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and (4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken together, our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis, and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria. ischemic stroke; microglia; mitochondria transplantation; neurogenesis; pyroptosis Neurology. Diseases of the nervous system Zhaoyan Zhao verfasserin aut Jing Guo verfasserin aut Yuan Qin verfasserin aut Qian Yu verfasserin aut Xiaolong Shi verfasserin aut Fei Guo verfasserin aut Haiqin Zhang verfasserin aut Xude Sun verfasserin aut Changjun Gao verfasserin aut Qian Yang verfasserin aut In Neural Regeneration Research Wolters Kluwer Medknow Publications, 2014 19(2024), 6, Seite 1325-1335 (DE-627)545785499 (DE-600)2388460-5 18767958 nnns volume:19 year:2024 number:6 pages:1325-1335 https://doi.org/10.4103/1673-5374.385313 kostenfrei https://doaj.org/article/6bd9120fb8fc4ab4a20cba8848f9225b kostenfrei http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=6;spage=1325;epage=1335;aulast=Sun kostenfrei https://doaj.org/toc/1673-5374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2700 GBV_ILN_2817 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2024 6 1325-1335
spelling	10.4103/1673-5374.385313 doi (DE-627)DOAJ095809112 (DE-599)DOAJ6bd9120fb8fc4ab4a20cba8848f9225b DE-627 ger DE-627 rakwb eng RC346-429 Li Sun verfasserin aut Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier [INLINE:1] Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site (in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9 (S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that: (1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis; (2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function; (3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and (4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken together, our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis, and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria. ischemic stroke; microglia; mitochondria transplantation; neurogenesis; pyroptosis Neurology. Diseases of the nervous system Zhaoyan Zhao verfasserin aut Jing Guo verfasserin aut Yuan Qin verfasserin aut Qian Yu verfasserin aut Xiaolong Shi verfasserin aut Fei Guo verfasserin aut Haiqin Zhang verfasserin aut Xude Sun verfasserin aut Changjun Gao verfasserin aut Qian Yang verfasserin aut In Neural Regeneration Research Wolters Kluwer Medknow Publications, 2014 19(2024), 6, Seite 1325-1335 (DE-627)545785499 (DE-600)2388460-5 18767958 nnns volume:19 year:2024 number:6 pages:1325-1335 https://doi.org/10.4103/1673-5374.385313 kostenfrei https://doaj.org/article/6bd9120fb8fc4ab4a20cba8848f9225b kostenfrei http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=6;spage=1325;epage=1335;aulast=Sun kostenfrei https://doaj.org/toc/1673-5374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2700 GBV_ILN_2817 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2024 6 1325-1335
allfields_unstemmed	10.4103/1673-5374.385313 doi (DE-627)DOAJ095809112 (DE-599)DOAJ6bd9120fb8fc4ab4a20cba8848f9225b DE-627 ger DE-627 rakwb eng RC346-429 Li Sun verfasserin aut Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier [INLINE:1] Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site (in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9 (S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that: (1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis; (2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function; (3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and (4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken together, our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis, and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria. ischemic stroke; microglia; mitochondria transplantation; neurogenesis; pyroptosis Neurology. Diseases of the nervous system Zhaoyan Zhao verfasserin aut Jing Guo verfasserin aut Yuan Qin verfasserin aut Qian Yu verfasserin aut Xiaolong Shi verfasserin aut Fei Guo verfasserin aut Haiqin Zhang verfasserin aut Xude Sun verfasserin aut Changjun Gao verfasserin aut Qian Yang verfasserin aut In Neural Regeneration Research Wolters Kluwer Medknow Publications, 2014 19(2024), 6, Seite 1325-1335 (DE-627)545785499 (DE-600)2388460-5 18767958 nnns volume:19 year:2024 number:6 pages:1325-1335 https://doi.org/10.4103/1673-5374.385313 kostenfrei https://doaj.org/article/6bd9120fb8fc4ab4a20cba8848f9225b kostenfrei http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=6;spage=1325;epage=1335;aulast=Sun kostenfrei https://doaj.org/toc/1673-5374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2700 GBV_ILN_2817 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2024 6 1325-1335
allfieldsGer	10.4103/1673-5374.385313 doi (DE-627)DOAJ095809112 (DE-599)DOAJ6bd9120fb8fc4ab4a20cba8848f9225b DE-627 ger DE-627 rakwb eng RC346-429 Li Sun verfasserin aut Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier [INLINE:1] Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site (in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9 (S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that: (1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis; (2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function; (3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and (4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken together, our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis, and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria. ischemic stroke; microglia; mitochondria transplantation; neurogenesis; pyroptosis Neurology. Diseases of the nervous system Zhaoyan Zhao verfasserin aut Jing Guo verfasserin aut Yuan Qin verfasserin aut Qian Yu verfasserin aut Xiaolong Shi verfasserin aut Fei Guo verfasserin aut Haiqin Zhang verfasserin aut Xude Sun verfasserin aut Changjun Gao verfasserin aut Qian Yang verfasserin aut In Neural Regeneration Research Wolters Kluwer Medknow Publications, 2014 19(2024), 6, Seite 1325-1335 (DE-627)545785499 (DE-600)2388460-5 18767958 nnns volume:19 year:2024 number:6 pages:1325-1335 https://doi.org/10.4103/1673-5374.385313 kostenfrei https://doaj.org/article/6bd9120fb8fc4ab4a20cba8848f9225b kostenfrei http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=6;spage=1325;epage=1335;aulast=Sun kostenfrei https://doaj.org/toc/1673-5374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2700 GBV_ILN_2817 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2024 6 1325-1335
allfieldsSound	10.4103/1673-5374.385313 doi (DE-627)DOAJ095809112 (DE-599)DOAJ6bd9120fb8fc4ab4a20cba8848f9225b DE-627 ger DE-627 rakwb eng RC346-429 Li Sun verfasserin aut Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier [INLINE:1] Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site (in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9 (S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that: (1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis; (2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function; (3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and (4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken together, our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis, and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria. ischemic stroke; microglia; mitochondria transplantation; neurogenesis; pyroptosis Neurology. Diseases of the nervous system Zhaoyan Zhao verfasserin aut Jing Guo verfasserin aut Yuan Qin verfasserin aut Qian Yu verfasserin aut Xiaolong Shi verfasserin aut Fei Guo verfasserin aut Haiqin Zhang verfasserin aut Xude Sun verfasserin aut Changjun Gao verfasserin aut Qian Yang verfasserin aut In Neural Regeneration Research Wolters Kluwer Medknow Publications, 2014 19(2024), 6, Seite 1325-1335 (DE-627)545785499 (DE-600)2388460-5 18767958 nnns volume:19 year:2024 number:6 pages:1325-1335 https://doi.org/10.4103/1673-5374.385313 kostenfrei https://doaj.org/article/6bd9120fb8fc4ab4a20cba8848f9225b kostenfrei http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=6;spage=1325;epage=1335;aulast=Sun kostenfrei https://doaj.org/toc/1673-5374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2700 GBV_ILN_2817 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2024 6 1325-1335
language	English
source	In Neural Regeneration Research 19(2024), 6, Seite 1325-1335 volume:19 year:2024 number:6 pages:1325-1335
sourceStr	In Neural Regeneration Research 19(2024), 6, Seite 1325-1335 volume:19 year:2024 number:6 pages:1325-1335
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	ischemic stroke; microglia; mitochondria transplantation; neurogenesis; pyroptosis Neurology. Diseases of the nervous system
isfreeaccess_bool	true
container_title	Neural Regeneration Research
authorswithroles_txt_mv	Li Sun @@aut@@ Zhaoyan Zhao @@aut@@ Jing Guo @@aut@@ Yuan Qin @@aut@@ Qian Yu @@aut@@ Xiaolong Shi @@aut@@ Fei Guo @@aut@@ Haiqin Zhang @@aut@@ Xude Sun @@aut@@ Changjun Gao @@aut@@ Qian Yang @@aut@@
publishDateDaySort_date	2024-01-01T00:00:00Z
hierarchy_top_id	545785499
id	DOAJ095809112
language_de	englisch
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Our data showed that: (1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis; (2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function; (3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and (4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. 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callnumber-first	R - Medicine
author	Li Sun
spellingShingle	Li Sun misc RC346-429 misc ischemic stroke; microglia; mitochondria transplantation; neurogenesis; pyroptosis misc Neurology. Diseases of the nervous system Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis
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topic_title	RC346-429 Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis ischemic stroke; microglia; mitochondria transplantation; neurogenesis; pyroptosis
topic	misc RC346-429 misc ischemic stroke; microglia; mitochondria transplantation; neurogenesis; pyroptosis misc Neurology. Diseases of the nervous system
topic_unstemmed	misc RC346-429 misc ischemic stroke; microglia; mitochondria transplantation; neurogenesis; pyroptosis misc Neurology. Diseases of the nervous system
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title	Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis
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title_full	Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis
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author_browse	Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang
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title_sort	mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis
callnumber	RC346-429
title_auth	Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis
abstract	[INLINE:1] Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site (in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9 (S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that: (1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis; (2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function; (3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and (4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken together, our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis, and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria.
abstractGer	[INLINE:1] Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site (in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9 (S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that: (1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis; (2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function; (3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and (4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken together, our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis, and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria.
abstract_unstemmed	[INLINE:1] Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site (in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9 (S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that: (1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis; (2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function; (3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and (4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken together, our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis, and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria.
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title_short	Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis
url	https://doi.org/10.4103/1673-5374.385313 https://doaj.org/article/6bd9120fb8fc4ab4a20cba8848f9225b http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=6;spage=1325;epage=1335;aulast=Sun https://doaj.org/toc/1673-5374
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author2	Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang
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up_date	2024-07-03T16:44:25.752Z
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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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