PMID- 31400488
OWN - NLM
STAT- MEDLINE
DCOM- 20200924
LR  - 20200924
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 417
DP  - 2019 Oct 1
TI  - HucMSCs-Derived miR-206-Knockdown Exosomes Contribute to Neuroprotection in 
      Subarachnoid Hemorrhage Induced Early Brain Injury by Targeting BDNF.
PG  - 11-23
LID - S0306-4522(19)30542-1 [pii]
LID - 10.1016/j.neuroscience.2019.07.051 [doi]
AB  - Early brain injury (EBI) is the most important potentially treatable cause of 
      mortality and morbidity following subarachnoid hemorrhage (SAH). Apoptosis is one 
      of the main pathologies of SAH-induced EBI. Numerous studies suggest that human 
      umbilical cord derived mesenchymal stem cells (hucMSCs) may exert neuroprotective 
      effect through exosomes instead of transdifferentiation. In addition, 
      microRNA-206 (miR-206) targets BDNF and plays a critical role in brain injury 
      diseases. However, the therapy effect of miR-206 modified exosomes on EBI after 
      SAH and its regulatory mechanism have not been elucidated. Here, to identify 
      whether hucMSCs-derived miR-206-knockdown exosomes have a better neuroprotective 
      effect, we established SAH rat model and treated it with the exosomes to research 
      the mechanism of miR-206 in EBI after SAH. We found that treatment with 
      hucMSCs-derived miR-206-knockdown exosomes has a greater neuroprotective effect 
      on SAH-induced EBI compared to treatment with simple exosomes. The 
      miR-206-knockdown exosomes could significantly improve neurological deficit and 
      brain edema and suppress neuronal apoptosis by targeting BDNF. Moreover, the 
      BDNF/TrkB/CREB pathway was activated following treatment with miR-206 modified 
      exosomes in vivo. In summary, these findings indicate that the hucMSCs-derived 
      miR-206-knockdown exosomes prevent early brain injury by inhibiting apoptosis via 
      BDNF/TrkB/CREB signaling. This may serve as a novel therapeutic target for 
      treatment of SAH-induced EBI.
CI  - Copyright (c) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Zhao, Hao
AU  - Zhao H
AD  - Department of Neurosurgery, The Seventh Medical Center of the PLA General 
      Hospital, Beijing, 100000, China.
FAU - Li, Yunjun
AU  - Li Y
AD  - Department of Neurosurgery, The Seventh Medical Center of the PLA General 
      Hospital, Beijing, 100000, China.
FAU - Chen, Lihua
AU  - Chen L
AD  - Department of Neurosurgery, The Seventh Medical Center of the PLA General 
      Hospital, Beijing, 100000, China.
FAU - Shen, Chunsen
AU  - Shen C
AD  - Department of Neurosurgery, The Seventh Medical Center of the PLA General 
      Hospital, Beijing, 100000, China.
FAU - Xiao, Zongyu
AU  - Xiao Z
AD  - Department of Neurosurgery, Affiliated Hospital of Qinghai University, Xining, 
      810000, China.
FAU - Xu, Ruxiang
AU  - Xu R
AD  - Department of Neurosurgery, The Seventh Medical Center of the PLA General 
      Hospital, Beijing, 100000, China.
FAU - Wang, Ji
AU  - Wang J
AD  - Department of Neurosurgery, The Seventh Medical Center of the PLA General 
      Hospital, Beijing, 100000, China; Department of Neurosurgery, The Second 
      Affiliated Hospital of Soochow University, Suzhou, 215004, China. Electronic 
      address: neuro-wangji@hotmail.com.
FAU - Luo, Yongchun
AU  - Luo Y
AD  - Department of Neurosurgery, The Seventh Medical Center of the PLA General 
      Hospital, Beijing, 100000, China. Electronic address: lyc81nk@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190807
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (mirn206 microRNA, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Brain/metabolism
MH  - Brain Edema/pathology
MH  - Brain Injuries/pathology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Exosomes/*genetics/metabolism/*transplantation
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Male
MH  - Membrane Glycoproteins/metabolism
MH  - Mesenchymal Stem Cells
MH  - MicroRNAs/*metabolism
MH  - Neuroprotection/*physiology
MH  - Neuroprotective Agents/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/metabolism
MH  - Signal Transduction
MH  - Subarachnoid Hemorrhage/*metabolism/pathology/*therapy
OTO - NOTNLM
OT  - brain-derived neurotrophic factor
OT  - early brain injury
OT  - exosomes
OT  - miR-206
OT  - subarachnoid hemorrhage
EDAT- 2019/08/11 06:00
MHDA- 2020/09/25 06:00
CRDT- 2019/08/11 06:00
PHST- 2019/04/19 00:00 [received]
PHST- 2019/07/30 00:00 [revised]
PHST- 2019/07/31 00:00 [accepted]
PHST- 2019/08/11 06:00 [pubmed]
PHST- 2020/09/25 06:00 [medline]
PHST- 2019/08/11 06:00 [entrez]
AID - S0306-4522(19)30542-1 [pii]
AID - 10.1016/j.neuroscience.2019.07.051 [doi]
PST - ppublish
SO  - Neuroscience. 2019 Oct 1;417:11-23. doi: 10.1016/j.neuroscience.2019.07.051. Epub 
      2019 Aug 7.