PMID- 31801411 OWN - NLM STAT- MEDLINE DCOM- 20210510 LR - 20210510 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 29 IP - 4 DP - 2020 Feb 15 TI - Exosomes from Bone Marrow Mesenchymal Stem Cells Can Alleviate Early Brain Injury After Subarachnoid Hemorrhage Through miRNA129-5p-HMGB1 Pathway. PG - 212-221 LID - 10.1089/scd.2019.0206 [doi] AB - In this study, the roles of exosomes (Exo) from bone marrow mesenchymal stem cells (BMSCs) in attenuating early brain injury (EBI) in rat brain after subarachnoid hemorrhage (SAH) had been investigated. The male Sprague-Dawley rats (300-350 g) were used to establish the SAH model using endovascular perforation method. The animals were randomly divided into three groups: sham (n = 25), SAH+PBS (n = 42), and SAH+Exo groups (n = 33). At 1 h after SAH, Exo or phosphate-buffered saline (PBS) was administered by femoral vein injection. The effects of Exo on the mortality, neurological function, brain water content, and blood-brain barrier (BBB) were explored. Furthermore, the expressions of miRNA129-5p and high-mobility group box 1 protein (HMGB1) after Exo treatment were also detected. In addition, immunohistochemistry and western blot were applied to investigate the mechanism of Exo's effects. The results indicated that Exo could improve the neurological functions, reduce brain water content and maintain BBB integrity after SAH. After Exo treatment, the expression of miRNA129-5p was significantly increased, whereas the RNA level of HMGB1 was decreased. The protein levels of proinflammatory and proapoptosis factors, such as HMGB1, Toll-like receptor-4 (TLR4), tumor necrosis factor-alpha, and p53, were increased after SAH, which were significantly declined after Exo application. The results indicated that Exo from BMSCs could alleviate EBI after SAH through miRNA129-5p's anti-inflammation and antiapoptosis effects through quenching the activity of HMGB1-TLR4 pathway. FAU - Xiong, Lili AU - Xiong L AD - Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China. FAU - Sun, Linlin AU - Sun L AD - Department of Anatomy and Histology, School of Basic Medical Sciences, Peking University, Beijing, China. FAU - Zhang, Yixuan AU - Zhang Y AD - Department of Anatomy and Histology, School of Basic Medical Sciences, Peking University, Beijing, China. FAU - Peng, Jin AU - Peng J AD - Department of Histology and Embryology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China. FAU - Yan, Junhao AU - Yan J AD - Department of Anatomy and Histology, School of Basic Medical Sciences, Peking University, Beijing, China. FAU - Liu, Xiaoheng AU - Liu X AD - Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191230 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (Culture Media, Conditioned) RN - 0 (HMGB1 Protein) RN - 0 (Hbp1 protein, rat) RN - 0 (MIRN129 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (Tlr4 protein, rat) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Animals MH - Blood-Brain Barrier/metabolism MH - Bone Marrow Cells/cytology/*metabolism MH - Brain Injuries/genetics/mortality/pathology/*therapy MH - Culture Media, Conditioned/chemistry/metabolism MH - Exosomes/metabolism/*transplantation MH - Gene Expression Regulation MH - HMGB1 Protein/*genetics/metabolism MH - Male MH - Mesenchymal Stem Cells/cytology/*metabolism MH - MicroRNAs/*genetics/metabolism MH - Permeability MH - Primary Cell Culture MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction MH - Subarachnoid Hemorrhage, Traumatic/genetics/mortality/pathology/*therapy MH - Survival Analysis MH - Toll-Like Receptor 4/genetics/metabolism OTO - NOTNLM OT - blood-brain barrier OT - bone marrow mesenchymal stem cell OT - exosome OT - subarachnoid hemorrhage EDAT- 2019/12/06 06:00 MHDA- 2021/05/11 06:00 CRDT- 2019/12/06 06:00 PHST- 2019/12/06 06:00 [pubmed] PHST- 2021/05/11 06:00 [medline] PHST- 2019/12/06 06:00 [entrez] AID - 10.1089/scd.2019.0206 [doi] PST - ppublish SO - Stem Cells Dev. 2020 Feb 15;29(4):212-221. doi: 10.1089/scd.2019.0206. Epub 2019 Dec 30.