PMID- 26654668
OWN - NLM
STAT- MEDLINE
DCOM- 20161104
LR  - 20181202
IS  - 1532-8511 (Electronic)
IS  - 1052-3057 (Linking)
VI  - 25
IP  - 2
DP  - 2016 Feb
TI  - Neuroprotective Effects of Brain-Derived Neurotrophic Factor and Noggin-Modified 
      Bone Mesenchymal Stem Cells in Focal Cerebral Ischemia in Rats.
PG  - 410-8
LID - S1052-3057(15)00552-2 [pii]
LID - 10.1016/j.jstrokecerebrovasdis.2015.10.013 [doi]
AB  - BACKGROUND: Administration of bone marrow stromal cells (BMSCs) has been reported 
      to ameliorate functional deficits in rat ischemia models. In the present study, 
      we tried to reveal the underlying mechanism of the improvement of neurological 
      function after stroke by BMSCs transfected with brain-derived neurotrophic factor 
      (BDNF) and/or Noggin. METHODS: BMSCs were transfected with BDNF or/and Noggin 
      using the adenovirus method. Middle cerebral artery occlusion (MCAO) rat models 
      were treated with different types of transfected BMSCs. The treatment effect was 
      assessed by measuring the modified Neurological Severity Score and the expression 
      levels of different stroke-related molecules using Western blot, 
      immunohistochemistry assay (IHC), and enzyme-linked immunosorbent assay (ELISA). 
      RESULTS: The injection of BDNF or/and Noggin-modified BMSCs could significantly 
      improve the neurological function of MCAO animals. Western blot and IHC staining 
      showed that the expression levels of vascular endothelial growth factor, BCL-2, 
      p-GSK3beta, and p-Akt were significantly upregulated, while the expressions of Bax, 
      TLR4, and MyD88 were significantly downregulated. Moreover, ELISA assay revealed 
      that the level of matrix metallopeptidase 9 (MMP-9) and reactive oxygen species 
      were also significantly decreased. These results suggested that the treatment of 
      BDNF or/and Noggin-modified BMSCs may suppress the ischemia-induced apoptosis and 
      inflammation in the model animals, which might be through the Akt/GSK3beta and 
      TLR4/MyD88 pathways. CONCLUSION: BDNF or/and Noggin-modified BMSCs may exert 
      neuroprotective effects through the Akt/GSK3beta and TLR4/MyD88 pathways. 
      Transplantation of BDNF or/and Noggin-modified BMSCs might be a potential 
      therapeutic method for ischemic stroke in clinics.
CI  - Copyright (c) 2015 National Stroke Association. Published by Elsevier Inc. All 
      rights reserved.
FAU - Lu, Hongyan
AU  - Lu H
AD  - Department of Neurology, Institute of Neurology, General Hospital of Tianjin 
      Medical University, Tianjin, China.
FAU - Liu, Xingmiao
AU  - Liu X
AD  - Department of pediatrics, Institute of Neurology; Tianjin Children's Hospital; 
      No. 225, Tianjin, China.
FAU - Zhang, Nan
AU  - Zhang N
AD  - Department of Neurology, Institute of Neurology, General Hospital of Tianjin 
      Medical University, Tianjin, China.
FAU - Zhu, Xiaodong
AU  - Zhu X
AD  - Department of Neurology, Institute of Neurology, General Hospital of Tianjin 
      Medical University, Tianjin, China.
FAU - Liang, Hao
AU  - Liang H
AD  - Department of Neurology, Institute of Neurology, General Hospital of Tianjin 
      Medical University, Tianjin, China.
FAU - Sun, Li
AU  - Sun L
AD  - Department of Neurology, Institute of Neurology, General Hospital of Tianjin 
      Medical University, Tianjin, China.
FAU - Cheng, Yan
AU  - Cheng Y
AD  - Department of Neurology, Institute of Neurology, General Hospital of Tianjin 
      Medical University, Tianjin, China. Electronic address: chengyan985@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151130
PL  - United States
TA  - J Stroke Cerebrovasc Dis
JT  - Journal of stroke and cerebrovascular diseases : the official journal of National 
      Stroke Association
JID - 9111633
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carrier Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 148294-77-3 (noggin protein)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Brain/metabolism
MH  - Brain Ischemia/*therapy
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Carrier Proteins/*genetics/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Neuroprotective Agents/*therapeutic use
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Treatment Outcome
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - bcl-2-Associated X Protein/metabolism
OTO - NOTNLM
OT  - Akt/GSK3beta
OT  - Brain-derived neurotrophic factor
OT  - Noggin
OT  - TLR4/MyD88
OT  - bone marrow stromal cells
OT  - focal cerebral ischemia
OT  - neuroprotection
EDAT- 2015/12/15 06:00
MHDA- 2016/11/05 06:00
CRDT- 2015/12/15 06:00
PHST- 2015/05/19 00:00 [received]
PHST- 2015/09/09 00:00 [revised]
PHST- 2015/10/17 00:00 [accepted]
PHST- 2015/12/15 06:00 [entrez]
PHST- 2015/12/15 06:00 [pubmed]
PHST- 2016/11/05 06:00 [medline]
AID - S1052-3057(15)00552-2 [pii]
AID - 10.1016/j.jstrokecerebrovasdis.2015.10.013 [doi]
PST - ppublish
SO  - J Stroke Cerebrovasc Dis. 2016 Feb;25(2):410-8. doi: 
      10.1016/j.jstrokecerebrovasdis.2015.10.013. Epub 2015 Nov 30.