PMID- 34583153 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231221 IS - 1879-2472 (Electronic) IS - 0049-3848 (Linking) VI - 207 DP - 2021 Nov TI - Brain-derived extracellular vesicles mediated coagulopathy, inflammation and apoptosis after sepsis. PG - 85-95 LID - S0049-3848(21)00466-7 [pii] LID - 10.1016/j.thromres.2021.09.014 [doi] AB - INTRODUCTION: The activation of coagulation, inflammation and other pathways is the basic response of the host to infection in sepsis, but this response also causes damage to the host. Brain-derived extracellular vesicles (BDEVs) have been reported to cause a hypercoagulable state that can rapidly develop into consumptive coagulopathy, which is consistent with the pathophysiological process of sepsis-induced coagulopathy. However, the role of BDEVs in sepsis-induced coagulopathy remains unclear. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were used for sepsis modeling using cecal ligation puncture (CLP). Flow cytometry was used to measure the levels of circulating BDEVs. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of plasminogen activator inhibitor type 1 (PAI-1), thrombin-antithrombin (TAT), D-dimer, fibrinogen(Fib), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6. Nanoparticle tracking analysis (NTA) and Transmission electron microscopy (TEM) were used to identify BDEVs. Western blot (WB) was used to determine the expression of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), bax, bcl-2 and cleaved caspase-3. Hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining were performed to detect tissue injury. Survival was monitored over the course of 168 h. RESULTS: We found that a large number of BDEVs were released into the circulating blood in septic rats. Moreover, we observed that BDEVs injection activated the systemic coagulation reaction and induced lung, liver and kidney inflammation and apoptosis(P < .05). Compared with BDEVs from sham-operated rats, BDEVs from septic rats exacerbated this process(P < .05). CONCLUSIONS: This finding suggests that inhibiting BDEVs may yield therapeutic benefits in the treatment of sepsis-induced coagulopathy. CI - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Lin, Huaying AU - Lin H AD - Department of Anesthesia, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China. FAU - Chen, Hongguang AU - Chen H AD - Department of Anesthesia, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China. FAU - Qi, Bo AU - Qi B AD - Department of Anesthesia, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China. FAU - Jiang, Yi AU - Jiang Y AD - Department of Anesthesia, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China. FAU - Lian, Naqi AU - Lian N AD - Department of Anesthesia, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China. FAU - Zhuang, Xiaoli AU - Zhuang X AD - Department of Anesthesia, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China. FAU - Yu, Yonghao AU - Yu Y AD - Department of Anesthesia, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: yyu@tmu.edu.cn. LA - eng PT - Journal Article DEP - 20210923 PL - United States TA - Thromb Res JT - Thrombosis research JID - 0326377 SB - IM OTO - NOTNLM OT - Apoptosis OT - Coagulopathy OT - Extracellular vesicles OT - Inflammation OT - Sepsis EDAT- 2021/09/29 06:00 MHDA- 2021/09/29 06:01 CRDT- 2021/09/28 20:22 PHST- 2021/06/04 00:00 [received] PHST- 2021/09/14 00:00 [revised] PHST- 2021/09/20 00:00 [accepted] PHST- 2021/09/29 06:01 [medline] PHST- 2021/09/29 06:00 [pubmed] PHST- 2021/09/28 20:22 [entrez] AID - S0049-3848(21)00466-7 [pii] AID - 10.1016/j.thromres.2021.09.014 [doi] PST - ppublish SO - Thromb Res. 2021 Nov;207:85-95. doi: 10.1016/j.thromres.2021.09.014. Epub 2021 Sep 23.