PMID- 26620543
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20161230
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1631
DP  - 2016 Jan 15
TI  - A human neural stem cell line provides neuroprotection and improves neurological 
      performance by early intervention of neuroinflammatory system.
PG  - 194-203
LID - S0006-8993(15)00878-1 [pii]
LID - 10.1016/j.brainres.2015.11.031 [doi]
AB  - A human neural stem cell line, HB1.F3, demonstrated neuroprotective properties in 
      cerebral ischemia animal models. In this study, we have investigated about the 
      mechanisms of such neuroprotection, mainly focusing on the neuroinflammatory 
      system at an earlier time point of the pathology. Cerebral ischemia model was 
      generated by middle cerebral artery occlusion (MCAO) in adult male Wister rats. 
      HB1.F3 cells were transplanted through jugular vein 6h after MCAO. Forty eight 
      hours after MCAO, transplanted rats showed better neurological performance and 
      decreased TUNEL positive apoptotic cell number in the penumbra. However, 
      haematoxylin and eosin staining and immunostaining showed that, HB1.F3 cells did 
      not affect the necrotic cell death. Twenty four hours after MCAO (18h after 
      HB1.F3 transplantation), infiltrated granulocytes and macrophage/microglia number 
      in the core regions were decreased compared to PBS-treated controls. 
      Immunohistochemical analysis further demonstrated that the transplantation 
      decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 
      expressing cell number in the core and penumbra, respectively. Double 
      immunofluorescence results revealed that iNOS was mainly expressed in 
      granulocytes and macrophage/microglia in the core region, and COX-2 mainly 
      expressed in neurons, endothelial cells and granulocytes in penumbra. Further 
      analysis showed that although the percentage of iNOS expressing granulocytes and 
      macrophage/microglia was not decreased, COX-2 expressing neurons and vessel 
      number was decreased by the transplantation. In vitro mRNA analysis showed that 
      brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (betaFGF) 
      and bone morphogenic protein (BMP)-4 expression was high in cultured HB1.F3 
      cells. Thus, our results demonstrated that HB1.F3 cell transplantation provide 
      neuroprotection possibly through the regulation of early inflammatory events in 
      the cerebral ischemia condition.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Watanabe, Tatsuzo
AU  - Watanabe T
AD  - Department of Internal Medicine III, Shimane University School of Medicine, 89-1 
      Enya Cho, Izumo 693-8501, Japan.
FAU - Nagai, Atsushi
AU  - Nagai A
AD  - Department of Laboratory Medicine, Shimane University School of Medicine, 89-1 
      Enya Cho, Izumo 693-8501, Japan. Electronic address: anagai@med.shimane-u.ac.jp.
FAU - Sheikh, Abdullah Md
AU  - Sheikh AM
AD  - Department of Laboratory Medicine, Shimane University School of Medicine, 89-1 
      Enya Cho, Izumo 693-8501, Japan.
FAU - Mitaki, Shingo
AU  - Mitaki S
AD  - Department of Internal Medicine III, Shimane University School of Medicine, 89-1 
      Enya Cho, Izumo 693-8501, Japan.
FAU - Wakabayashi, Kiryo
AU  - Wakabayashi K
AD  - Department of Internal Medicine III, Shimane University School of Medicine, 89-1 
      Enya Cho, Izumo 693-8501, Japan.
FAU - Kim, Seung U
AU  - Kim SU
AD  - Department of Neurology, UBC Hospital, University of British Columbia, Vancouver, 
      Canada; Medical Research Institute, Chung-Ang University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Kobayashi, Shotai
AU  - Kobayashi S
AD  - Department of Internal Medicine III, Shimane University School of Medicine, 89-1 
      Enya Cho, Izumo 693-8501, Japan.
FAU - Yamaguchi, Shuhei
AU  - Yamaguchi S
AD  - Department of Internal Medicine III, Shimane University School of Medicine, 89-1 
      Enya Cho, Izumo 693-8501, Japan.
LA  - eng
PT  - Journal Article
DEP - 20151124
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Ptgs2 protein, rat)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/immunology/metabolism/pathology/*prevention & control
MH  - Cell Line
MH  - Cyclooxygenase 2/metabolism
MH  - Disease Models, Animal
MH  - Granulocytes/metabolism
MH  - Humans
MH  - Infarction, Middle Cerebral Artery/immunology/metabolism/pathology/*therapy
MH  - Macrophages/metabolism
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Microglia/metabolism/pathology
MH  - Neural Stem Cells/cytology/*transplantation
MH  - Neuroimmunomodulation
MH  - Neurons/metabolism/pathology
MH  - Neuroprotection
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - HB1.F3 cells
OT  - Middle cerebral artery occlusion
OT  - Neural stem cell
OT  - Neuroinflammation
OT  - Neuroprotection
EDAT- 2015/12/02 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/12/02 06:00
PHST- 2015/07/22 00:00 [received]
PHST- 2015/11/12 00:00 [revised]
PHST- 2015/11/18 00:00 [accepted]
PHST- 2015/12/02 06:00 [entrez]
PHST- 2015/12/02 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - S0006-8993(15)00878-1 [pii]
AID - 10.1016/j.brainres.2015.11.031 [doi]
PST - ppublish
SO  - Brain Res. 2016 Jan 15;1631:194-203. doi: 10.1016/j.brainres.2015.11.031. Epub 
      2015 Nov 24.