PMID- 31229624
OWN - NLM
STAT- MEDLINE
DCOM- 20200203
LR  - 20200203
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 708
DP  - 2019 Aug 24
TI  - Nitrogen-doped carbon nanocages and human umbilical cord mesenchymal stem cells 
      cooperatively inhibit neuroinflammation and protect against ischemic stroke.
PG  - 134346
LID - S0304-3940(19)30447-1 [pii]
LID - 10.1016/j.neulet.2019.134346 [doi]
AB  - AIMS: This study aimed to explore the synergistic effects of nitrogen-doped 
      carbon nanocages (NCNCs) and human umbilical cord mesenchymal stem cells 
      (HUC-MSCs) on ischemic stroke and investigate the potential underlying 
      mechanisms. MAIN METHODS: The properties of NCNCs were analyzed by transmission 
      electron microscopy, and the markers of HUC-MSCs were detected by flow cytometry. 
      The cell toxicity of NCNCs was evaluated by MTT. Mice were induced cerebral 
      infarction by transient middle cerebral artery occlusion (MCAO). NCNCs or 
      HUC-MSCs or HUC-MSCs-NCNCs were intravenously injected thirty minutes after 
      reperfusion. The infarct volume was examined by 2,3,5-triphenyltetrazolium 
      chloride (TTC) staining, and behavior tests were evaluated by the modified 
      Neurological Severity Score (mNSS) and rotarod test. The mRNA levels of TNF-alpha and 
      IL-10 were detected by real-time PCR. The protein levels of TNF-alpha stimulated 
      gene/protein 6 (TSG-6) and prostaglandin 2 (PGE2) were detected by ELISA. The 
      microglia markers (CD86 and CD206) and the protein levels of TNF-alpha and IL-10 were 
      examined by flow cytometry. The protein levels of Iba1 and CD16 were determined 
      by immunostaining. KEY FINDINGS: NCNCs enhanced the therapeutic effects of 
      HUC-MSCs on MCAO mice, including reducing infarct volume, improving behavior 
      scores and inhibiting inflammation response. In addition, NCNCs and HUC-MSCs 
      cooperatively inhibit the mRNA and protein levels of TNF-alpha, and increased the 
      mRNA and protein levels of IL-10 and protein levels of PGE2 and TSG-6 in 
      LPS-treated microglia. Furthermore, NCNCs exerted synergistic effects with 
      HUC-MSCs on remodeling microglia polarization. SIGNIFICANCE: NCNCs enhance the 
      therapeutic effects of HUC-MSCs on cerebral infarction in a mouse MCAO model, and 
      inhibit the microglia reactivation and neuroinflammation, which indicates it as a 
      potential treatment for ischemic stroke.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Zhai, Lili
AU  - Zhai L
AD  - Department of Neurology, Drum Tower Hospital, Medical School of Nanjing 
      University, Nanjing, Jiangsu 210008, PR China; Jiangsu Key Laboratory for 
      Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 
      210008, PR China. Electronic address: 15850770596@163.com.
FAU - Maimaitiming, Zaitunamu
AU  - Maimaitiming Z
AD  - Department of Neurology, Drum Tower Hospital, Medical School of Nanjing 
      University, Nanjing, Jiangsu 210008, PR China; Jiangsu Key Laboratory for 
      Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 
      210008, PR China. Electronic address: zaitunam@163.com.
FAU - Cao, Xiang
AU  - Cao X
AD  - Department of Neurology, Drum Tower Hospital, Medical School of Nanjing 
      University, Nanjing, Jiangsu 210008, PR China; Jiangsu Key Laboratory for 
      Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 
      210008, PR China. Electronic address: Xiangcao1988@163.com.
FAU - Xu, Yun
AU  - Xu Y
AD  - Department of Neurology, Drum Tower Hospital, Medical School of Nanjing 
      University, Nanjing, Jiangsu 210008, PR China; Jiangsu Key Laboratory for 
      Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 
      210008, PR China. Electronic address: xuyun20042001@aliyun.com.
FAU - Jin, Jiali
AU  - Jin J
AD  - Department of Neurology, Drum Tower Hospital, Medical School of Nanjing 
      University, Nanjing, Jiangsu 210008, PR China; Jiangsu Key Laboratory for 
      Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 
      210008, PR China. Electronic address: jjllily@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190620
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 7440-44-0 (Carbon)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/etiology/metabolism/*prevention & control
MH  - *Carbon/chemistry
MH  - Cell Polarity
MH  - Cells, Cultured
MH  - *Cord Blood Stem Cell Transplantation
MH  - Humans
MH  - Infarction, Middle Cerebral Artery/complications
MH  - Inflammation/metabolism/therapy
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mice, Inbred C57BL
MH  - Microglia/physiology
MH  - *Nanostructures/chemistry/toxicity
MH  - Stroke/etiology/metabolism/*prevention & control
OTO - NOTNLM
OT  - HUC-MSCs
OT  - Ischemic stroke
OT  - NCNCs
OT  - Neuroinflammation
OT  - Synergistic effects
EDAT- 2019/06/24 06:00
MHDA- 2020/02/06 06:00
CRDT- 2019/06/24 06:00
PHST- 2019/03/29 00:00 [received]
PHST- 2019/06/17 00:00 [revised]
PHST- 2019/06/19 00:00 [accepted]
PHST- 2019/06/24 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/06/24 06:00 [entrez]
AID - S0304-3940(19)30447-1 [pii]
AID - 10.1016/j.neulet.2019.134346 [doi]
PST - ppublish
SO  - Neurosci Lett. 2019 Aug 24;708:134346. doi: 10.1016/j.neulet.2019.134346. Epub 
      2019 Jun 20.