PMID- 25790286
OWN - NLM
STAT- MEDLINE
DCOM- 20160204
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 3
DP  - 2015
TI  - Neuroprotective effects of oligodendrocyte progenitor cell transplantation in 
      premature rat brain following hypoxic-ischemic injury.
PG  - e0115997
LID - 10.1371/journal.pone.0115997 [doi]
LID - e0115997
AB  - Periventricular leukomalacia (PVL) is a common ischemic brain injury in premature 
      infants for which there is no effective treatment. The objective of this study 
      was to determine whether transplanted mouse oligodendrocyte progenitor cells 
      (OPCs) have neuroprotective effects in a rat model of PVL. Hypoxia-ischemia (HI) 
      was induced in 3-day-old rat pups by left carotid artery ligation, followed by 
      exposure to 6% oxygen for 2.5 h. Animals were assigned to OPC transplantation or 
      sham control groups and injected with OPCs or PBS, respectively, and sacrificed 
      up to 6 weeks later for immunohistochemical analysis to investigate the survival 
      and differentiation of transplanted OPCs. Apoptosis was evaluated by double 
      immunolabeling of brain sections for caspase-3 and neuronal nuclei (NeuN), while 
      proliferation was assessed using a combination of anti-Nestin and 
      -bromodeoxyuridine antibodies. The expression of brain-derived neurotrophic 
      factor (BDNF) and Bcl-2 was examined 7 days after OPC transplantation. The Morris 
      water maze was used to test spatial learning and memory. The results showed that 
      transplanted OPCs survived and formed a myelin sheath, and stimulated BDNF and 
      Bcl-2 expression and the proliferation of neural stem cells (NSC), while 
      inhibiting HI-induced neuronal apoptosis relative to control animals. Moreover, 
      deficits in spatial learning and memory resulting from HI were improved by OPC 
      transplantation. These results demonstrate an important neuroprotective role for 
      OPCs that can potentially be exploited in cell-based therapeutic approaches to 
      minimize HI-induced brain injury.
FAU - Chen, Long-Xia
AU  - Chen LX
AD  - Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 
      Shanghai, China; Key Laboratory of Neonatal Diseases, Ministry of Health, 
      Children's Hospital of Fudan University, Shanghai, China.
FAU - Ma, Si-Min
AU  - Ma SM
AD  - Department of Neonatology, Children's Hospital of Fudan University, Shanghai, 
      201102, China; Key Laboratory of Neonatal Diseases, Ministry of Health, 
      Children's Hospital of Fudan University, Shanghai, China.
FAU - Zhang, Peng
AU  - Zhang P
AD  - Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of 
      Fudan University, Shanghai, China.
FAU - Fan, Zi-Chuan
AU  - Fan ZC
AD  - Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 
      Shanghai, China.
FAU - Xiong, Man
AU  - Xiong M
AD  - Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of 
      Fudan University, Shanghai, China.
FAU - Cheng, Guo-Qiang
AU  - Cheng GQ
AD  - Department of Neonatology, Children's Hospital of Fudan University, Shanghai, 
      201102, China.
FAU - Yang, Yi
AU  - Yang Y
AD  - Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of 
      Fudan University, Shanghai, China.
FAU - Qiu, Zi-Long
AU  - Qiu ZL
AD  - Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese 
      Academy of Sciences, Shanghai, 200031, China.
FAU - Zhou, Wen-Hao
AU  - Zhou WH
AD  - Department of Neonatology, Children's Hospital of Fudan University, Shanghai, 
      201102, China; Key Laboratory of Neonatal Diseases, Ministry of Health, 
      Children's Hospital of Fudan University, Shanghai, China.
FAU - Li, Jin
AU  - Li J
AD  - Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150319
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Allografts
MH  - Animals
MH  - Apoptosis
MH  - Brain Ischemia/metabolism/pathology/*therapy
MH  - Brain-Derived Neurotrophic Factor/biosynthesis
MH  - Caspase 3/biosynthesis
MH  - Gene Expression Regulation
MH  - Mice
MH  - Neural Stem Cells/metabolism/pathology/*transplantation
MH  - Oligodendroglia/*metabolism/pathology
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis
MH  - Rats
MH  - *Stem Cell Transplantation
PMC - PMC4366232
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/03/20 06:00
MHDA- 2016/02/05 06:00
PMCR- 2015/03/19
CRDT- 2015/03/20 06:00
PHST- 2014/08/26 00:00 [received]
PHST- 2014/12/03 00:00 [accepted]
PHST- 2015/03/20 06:00 [entrez]
PHST- 2015/03/20 06:00 [pubmed]
PHST- 2016/02/05 06:00 [medline]
PHST- 2015/03/19 00:00 [pmc-release]
AID - PONE-D-14-37261 [pii]
AID - 10.1371/journal.pone.0115997 [doi]
PST - epublish
SO  - PLoS One. 2015 Mar 19;10(3):e0115997. doi: 10.1371/journal.pone.0115997. 
      eCollection 2015.