PMID- 23069268
OWN - NLM
STAT- MEDLINE
DCOM- 20140528
LR  - 20211203
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 22
IP  - 11
DP  - 2013
TI  - Restoration of intracortical and thalamocortical circuits after transplantation 
      of bone marrow mesenchymal stem cells into the ischemic brain of mice.
PG  - 2001-15
LID - 10.3727/096368912X657909 [doi]
AB  - Transplantation of bone marrow mesenchymal stem cells (BMSCs) provides a 
      promising regenerative medicine for stroke. Whether BMSC therapy could repair 
      ischemia-damaged neuronal circuits and recover electrophysiological activity has 
      largely been unknown. To address this issue, BMSCs were implanted into the 
      ischemic barrel cortex of adult mice 1 and 7 days after focal barrel cortex 
      stroke. Two days after the first transplantation (3 days after stroke), the 
      infarct volume determined by TTC staining was significantly smaller in 
      BMSC-treated compared to vehicle-treated stroke mice. The behavioral corner test 
      showed better long-term recovery of sensorimotor function in BMSC-treated mice. 
      Six weeks poststroke, thalamocortical slices were prepared and neuronal circuit 
      activity in the peri-infarct region of the barrel cortex was determined by 
      extracellular recordings of evoked field potentials. In BMSC-transplanted brain 
      slices, the ischemia-disrupted intracortical activity from layer 4 to layer 2/3 
      was noticeably recovered, and the thalamocortical circuit connection was also 
      partially restored. In contrast, much less and slower recovery was seen in 
      control animals of barrel cortex stroke. Immunohistochemical staining disclosed 
      that the density of neurons, axons, and blood vessels in the peri-infarct region 
      was significantly higher in BMSC-treated mice, accompanied with enhanced local 
      blood flow recovery. Western blotting showed that BMSC treatment increased the 
      expression of stromal cell-derived factor-1 (SDF-1), vascular endothelial growth 
      factor (VEGF), and brain-derived neurotrophic factor (BDNF) in the peri-infarct 
      region. Moreover, the expression of the axonal growth associated protein-43 
      (GAP-43) was markedly increased, whereas the axonal growth inhibiting proteins 
      ROCK II and NG2 were suppressed in the BMSC-treated brains. BMSC transplantation 
      also promoted directional migration and survival of doublecortin (DCX)-positive 
      neuroblasts in the peri-infarct region. The present investigation thus provides 
      novel evidence that BMSC transplantation has the potential to repair the 
      ischemia-damaged neural networks and restore lost neuronal connections. The 
      recovered circuit activity likely contributes to the improved sensorimotor 
      function after focal ischemic stroke and BMSC transplantation.
FAU - Song, Mingke
AU  - Song M
AD  - Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, 
      USA.
FAU - Mohamad, Osama
AU  - Mohamad O
FAU - Gu, Xiaohuan
AU  - Gu X
FAU - Wei, Ling
AU  - Wei L
FAU - Yu, Shan Ping
AU  - Yu SP
LA  - eng
GR  - NS045810/NS/NINDS NIH HHS/United States
GR  - NS055077/NS/NINDS NIH HHS/United States
GR  - NS057255/NS/NINDS NIH HHS/United States
GR  - NS058710/NS/NINDS NIH HHS/United States
GR  - NS062097/NS/NINDS NIH HHS/United States
GR  - NS075338/NS/NINDS NIH HHS/United States
GR  - R41NS073378/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121012
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Antigens)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Dcx protein, mouse)
RN  - 0 (Doublecortin Protein)
RN  - 0 (GAP-43 Protein)
RN  - 0 (Proteoglycans)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (chondroitin sulfate proteoglycan 4)
RN  - EC 2.7.11.1 (Rock2 protein, mouse)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Animals
MH  - Antigens/metabolism
MH  - Axons/pathology
MH  - Blood Vessels/pathology
MH  - Bone Marrow Cells/*cytology
MH  - Brain Ischemia/metabolism/physiopathology/*therapy
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cells, Cultured
MH  - Chemokine CXCL12/metabolism
MH  - Doublecortin Protein
MH  - GAP-43 Protein/metabolism
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*cytology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/pathology
MH  - Proteoglycans/metabolism
MH  - Stroke/*surgery
MH  - Transplantation, Homologous
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - rho-Associated Kinases/metabolism
EDAT- 2012/10/17 06:00
MHDA- 2014/05/29 06:00
CRDT- 2012/10/17 06:00
PHST- 2012/10/17 06:00 [entrez]
PHST- 2012/10/17 06:00 [pubmed]
PHST- 2014/05/29 06:00 [medline]
AID - ct0684song [pii]
AID - 10.3727/096368912X657909 [doi]
PST - ppublish
SO  - Cell Transplant. 2013;22(11):2001-15. doi: 10.3727/096368912X657909. Epub 2012 
      Oct 12.