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

作     者：Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang Li Sun;Zhaoyan Zhao;Jing Guo;Yuan Qin;Qian Yu;Xiaolong Shi;Fei Guo;Haiqin Zhang;Xude Sun;Changjun Gao;Qian Yang

作者机构：Department of Experimental SurgeryThe Second Affiliated Hospital of Air Force Medical UniversityXi’anShaanxi ProvinceChina Department of AnesthesiologyThe Second Affiliated Hospital of Air Force Medical UniversityXi’anShaanxi ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2024年第19卷第6期

页      面：1325-1335页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,Nos.82201621(to LS),31930048(to QY)and 81720108016(to QY),and 81971225(to CG) the Key Research and Development Project of Shaanxi Province,No.2022SF-189(to XS) the Tangdu Hospital Supporting Foundation,Nos.2021ZTXM-006(to LS)and 2021JSZH-006(to CG) 

主　　题：ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis 

摘      要：Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion *** mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion ***,transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic *** 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,*** 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 *** between exogenous and endogenous mitochondria,as well as the effect of exogenous mitochondria on recipient microglia,were assessed in *** 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 ***