PMID- 32112178
OWN - NLM
STAT- MEDLINE
DCOM- 20210129
LR  - 20210129
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 45
IP  - 5
DP  - 2020 May
TI  - MSCs-Derived Exosomes Attenuate Acute Brain Injury and Inhibit Microglial 
      Inflammation by Reversing CysLT2R-ERK1/2 Mediated Microglia M1 Polarization.
PG  - 1180-1190
LID - 10.1007/s11064-020-02998-0 [doi]
AB  - Inflammatory responses play a major role in the pathophysiology of cerebral 
      ischemia. Mesenchymal stem cell-derived exosomes (MSC-exos) have important 
      anti-inflammatory effects on the treatment of organ injury. This study aimed to 
      determine the anti-inflammatory effect and furtherly investigate the potential 
      mechanism of MSC-exos on acute cerebral ischemia. MSC-exos were isolated by 
      ultracentrifugation, characterized by transmission electron microscopy and FACS. 
      Rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) surgery 
      were administered MSC-exos through the tail vein. In vitro, microglia exposed to 
      oxygen- and glucose-deprivation (OGD) and leukotrienes were used to study the 
      protective mechanism of exosomes against ischemia/reperfusion-induced 
      inflammation. The intake of exosomes into microglia was visualized through 
      immunofluorescence staining. The results showed that MSC-exos treatment 
      significantly improved motor, learning and memory abilities of MCAO/R rats 7 days 
      later. The production of pro-inflammatory factors decreased, while the 
      anti-inflammatory cytokines and neurotrophic factors increased both in the cortex 
      and hippocampus of ischemic hemisphere as well as in the culture supernatant of 
      microglia treated with OGD and NMLTC4. MSC-exos treatment also significantly 
      inhibited M1 microglia polarization and increased M2 microglia cells. 
      Furthermore, western blot analysis demonstrated that CysLT(2)R expression and 
      ERK1/2 phosphorylation were downregulated both in vivo and in vitro. Thus, 
      MSC-exos attenuated brain injury and inhibited microglial inflammation by 
      reversing CysLT(2)R-ERK1/2 mediated microglia M1 polarization.
FAU - Zhao, Yangmin
AU  - Zhao Y
AD  - School of Clinical Sciences, Hangzhou Medical College, Zhejiang, China.
FAU - Gan, Yunxiao
AU  - Gan Y
AD  - School of Pharmaceutical Sciences, Hangzhou Medical College, Zhejiang, China.
FAU - Xu, Gewei
AU  - Xu G
AD  - School of Clinical Sciences, Hangzhou Medical College, Zhejiang, China.
FAU - Yin, Guoli
AU  - Yin G
AD  - Shcool of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, 
      Zhejiang, China.
FAU - Liu, Dandan
AU  - Liu D
AD  - Shcool of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, 
      Zhejiang, China. 7559220@qq.com.
LA  - eng
GR  - No. LY18H090011/Natural Science Foundation of Zhejiang Province/
GR  - No. 2014ZA018/Zhejiang Traditional Chinese Medicine Administration/
GR  - No. 81201408/National Outstanding Youth Science Fund Project of National Natural 
      Science Foundation of China (CN)/
GR  - No. 2012C23104/Science Technology Department of Zhejiang Province/
PT  - Journal Article
DEP - 20200228
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, Leukotriene)
RN  - AJT72OTM42 (cysteinyl leukotriene receptor 2)
SB  - IM
MH  - Animals
MH  - Brain Injuries/*metabolism/therapy
MH  - Cell Polarity
MH  - Cells, Cultured
MH  - Exosomes/*transplantation
MH  - Inflammation/metabolism/therapy
MH  - Inflammation Mediators/antagonists & inhibitors/metabolism
MH  - MAP Kinase Signaling System/*physiology
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mesenchymal Stem Cells
MH  - Microglia/*metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Leukotriene/*metabolism
OTO - NOTNLM
OT  - CysLT2R
OT  - Exosome
OT  - Inflammation
OT  - M1 microglia polarization
OT  - MSCs
EDAT- 2020/03/01 06:00
MHDA- 2021/01/30 06:00
CRDT- 2020/03/01 06:00
PHST- 2019/09/09 00:00 [received]
PHST- 2020/02/24 00:00 [accepted]
PHST- 2020/02/15 00:00 [revised]
PHST- 2020/03/01 06:00 [pubmed]
PHST- 2021/01/30 06:00 [medline]
PHST- 2020/03/01 06:00 [entrez]
AID - 10.1007/s11064-020-02998-0 [pii]
AID - 10.1007/s11064-020-02998-0 [doi]
PST - ppublish
SO  - Neurochem Res. 2020 May;45(5):1180-1190. doi: 10.1007/s11064-020-02998-0. Epub 
      2020 Feb 28.