BACKGROUND: Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury. Mesenchymal stem cell (MSC) transplantation is used to reduce tissue damage, but exosomes are more stable and highly conserved than MSCs. This study was conducted to investigate the therapeutic effects of MSC-derived exosomes (MSC-Exo) on cerebral ischemia-reperfusion injury in an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R), and to explore the underlying mechanisms. METHODS: Primary hippocampal neurons obtained from 18-day Sprague-Dawley rat embryos were subjected to OGD/R treatment, with or without MSC-Exo treatment. Exosomal integration, cell viability, mitochondrial membrane potential, and generation of reactive oxygen species (ROS) were examined. Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling (TUNEL) staining was performed to detect neuronal apoptosis. Moreover, mitochondrial function-associated gene expression, Nrf2 translocation, and expression of downstream antioxidant proteins were determined. RESULTS: MSC-Exo attenuated OGD/R-induced neuronal apoptosis and decreased ROS generation (P<0.05). The exosomes reduced OGD/R-induced Nrf2 translocation into the nucleus (2.14±0.65 vs. 5.48±1.09, P<0.01) and increased the intracellular expression of antioxidative proteins, including superoxide dismutase and glutathione peroxidase (17.18±0.97 vs. 14.40±0.62, and 20.65±2.23 vs. 16.44±2.05, respectively; P<0.05 for both). OGD/R significantly impaired the mitochondrial membrane potential and modulated the expression of mitochondrial function-associated genes, such as PINK, DJ1, LRRK2, Mfn-1, Mfn-2, and OPA1. The abovementioned changes were partially reversed by exosomal treatment of the hippocampal neurons. CONCLUSIONS: MSC-Exo treatment can alleviate OGD/R-induced oxidative stress and dysregulation of mitochondrial function-associated genes in hippocampal neurons. Therefore, MSC-Exo might be a potential therapeutic strategy to prevent OGD/R-induced neuronal injury.

Xiao-fang Guo;Shuang-shuang Gu;Jun Wang;Hao Sun;Yu-juan Zhang;Peng-fei Yu;Jin-song Zhang;Lei Jiang

Department of Emergency,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;Key Laboratory of Modern Toxicology,Ministry of Education,Department of Toxicology,School of Public Health,Nanjing Medical University,Nanjing 211166,China;Key Laboratory of Modern Toxicology,Ministry of Education,Department of Environmental Genomics,School of Public Health,Nanjing Medical University,Nanjing 211166,China;Center for Drug Safety Evaluation and Research,Shanghai Institute of Materia Medica,Shanghai 201203,China

世界急诊医学杂志（英文）

[1]Xiao-fang Guo;Shuang-shuang Gu;Jun Wang;Hao Sun;Yu-juan Zhang;Peng-fei Yu;Jin-song Zhang;Lei Jiang-.Protective effect of mesenchymal stem cell-derived exosomal treatment of hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury)[J].世界急诊医学杂志（英文）,2022(01):46-53

DJ1

Protective,mesenchymal,stem,derived,exosomal,treatment,hippocampal,neurons,against,oxygen,glucose,deprivation,reperfusion,induced,injury,BACKGROUND,Individuals,who,survive,cardiac,arrest,often,sustain,cognitive,impairments,due,ischemia,Mesenchymal,transplantation,used,tissue,damage,but,exosomes,are,more,stable,highly,conserved,than,MSCs,This,study,was,conducted,investigate,therapeutic,effects,cerebral,vitro,model,OGD,explore,underlying,mechanisms,METHODS,Primary,obtained,from,day,Sprague,Dawley,embryos,were,subjected,without,Exosomal,integration,viability,mitochondrial,membrane,potential,generation,reactive,species,ROS,examined,Terminal,deoxynucleotidyl,transferase,mediated,deoxyuridine,triphosphate,nick,end,labeling,TUNEL,staining,performed,detect,neuronal,apoptosis,Moreover,function,associated,expression,Nrf2,translocation,downstream,antioxidant,proteins,determined,RESULTS,attenuated,decreased,reduced,into,nucleus,increased,intracellular,antioxidative,including,superoxide,dismutase,glutathione,peroxidase,respectively,both,significantly,impaired,modulated,genes,such,PINK,LRRK2,Mfn,OPA1,abovementioned,changes,partially,reversed,by,CONCLUSIONS,alleviate,stress,dysregulation,Therefore,might,strategy,prevent

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