PMID- 22683506
OWN - NLM
STAT- MEDLINE
DCOM- 20121022
LR  - 20131121
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 521
IP  - 2
DP  - 2012 Jul 19
TI  - Simvastatin mobilizes bone marrow stromal cells migrating to injured areas and 
      promotes functional recovery after spinal cord injury in the rat.
PG  - 136-41
LID - 10.1016/j.neulet.2012.05.071 [doi]
AB  - This study investigated the therapeutic effects of simvastatin administered by 
      subarachnoid injection after spinal cord injury (SCI) in rats; explored the 
      underlying mechanism from the perspective of mobilization, migration and homing 
      of bone marrow stromal cells (BMSCs) to the injured area induced by simvastatin. 
      Green fluorescence protein labeled-bone marrow stromal cells (GFP-BMSCs) were 
      transplanted into rats through the tail vein for stem cell tracing. Twenty-four 
      hours after transplantation, spinal cord injury (SCI) was produced using 
      weight-drop method (10g 4cm) at the T10 level. Simvastatin (5mg/kg) or vehicle 
      was administered by subarachnoid injection at lumbar level 4 after SCI. Locomotor 
      functional recovery was assessed in the 4 weeks following surgery using the 
      open-field test and inclined-plane test. At the end of the study, MRI was used to 
      evaluate the reparation of the injured spinal cord. Animals were then euthanized, 
      histological evaluation was used to measure lesion cavity volumes. 
      Immunofluorescence for GFP and cell lineage markers (NeuN and GFAP) was used to 
      evaluate simvastatin-mediated mobilization and differentiation of transplanted 
      BMSCs. Western blot and immunohistochemistry were used to assess the expression 
      of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic 
      factor (BDNF). Simvastatin-treated animals showed significantly better locomotor 
      recovery, less signal abnormality in MRI and a smaller cavity volume compared to 
      the control group. Immunofluorescence revealed that simvastatin increased the 
      number of GFP-positive cells in the injured spinal cord, and the number of cells 
      double positive for GFP/NeuN or GFP/GFAP was larger in the simvastatin treated 
      group than the control group. Western blot and immunohistochemistry showed higher 
      expression of BDNF and VEGF in the simvastatin treated group than the control 
      group. In conclusion, simvastatin can help to repair spinal cord injury in rat, 
      where the underlying mechanism appears to involve the mobilization of bone marrow 
      stromal cells to the injured area and higher expression of BNDF and VEGF.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Han, Xiaoguang
AU  - Han X
AD  - Department of Spine Surgery, Beijing Jishuitan Hospital, Tsinghua University, 
      Beijing 100035, China.
FAU - Yang, Ning
AU  - Yang N
FAU - Cui, Yueyi
AU  - Cui Y
FAU - Xu, Yingsheng
AU  - Xu Y
FAU - Dang, Gengting
AU  - Dang G
FAU - Song, Chunli
AU  - Song C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120605
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*drug effects/physiology
MH  - *Bone Marrow Transplantation
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Movement/drug effects
MH  - Female
MH  - Motor Activity/drug effects
MH  - Multipotent Stem Cells/*drug effects/physiology/transplantation
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Simvastatin/*pharmacology/therapeutic use
MH  - Spinal Cord/drug effects/metabolism/pathology
MH  - Spinal Cord Injuries/pathology/physiopathology/*therapy
MH  - Stromal Cells/drug effects/physiology/transplantation
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2012/06/12 06:00
MHDA- 2012/10/23 06:00
CRDT- 2012/06/12 06:00
PHST- 2012/03/24 00:00 [received]
PHST- 2012/05/16 00:00 [revised]
PHST- 2012/05/29 00:00 [accepted]
PHST- 2012/06/12 06:00 [entrez]
PHST- 2012/06/12 06:00 [pubmed]
PHST- 2012/10/23 06:00 [medline]
AID - S0304-3940(12)00754-9 [pii]
AID - 10.1016/j.neulet.2012.05.071 [doi]
PST - ppublish
SO  - Neurosci Lett. 2012 Jul 19;521(2):136-41. doi: 10.1016/j.neulet.2012.05.071. Epub 
      2012 Jun 5.