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Simvastatin mobilizes bone marrow stromal cells migrating to injured areas and promotes functional recovery after spinal cord injury in the rat
Han, Xiaoguang2; Yang, Ning3; Cui, Yueyi3; Xu, Yingsheng1; Dang, Gengting3; Song, Chunli3
关键词Spinal cord injury Simvastatin Stem cell Endogenous Homing Mobilization
刊名NEUROSCIENCE LETTERS
2012-07-19
DOI10.1016/j.neulet.2012.05.071
521期:2页:136-141
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]MESENCHYMAL STEM-CELLS ; NERVOUS-SYSTEM ; MICE ; REGENERATION ; BDNF ; DIFFERENTIATION ; TRANSPLANTATION ; STROKE ; VEGF
英文摘要

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 (10 g 4 cm) at the 110 level. Simvastatin (5 mg/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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

语种英语
WOS记录号WOS:000306583000009
项目编号81171693 ; 81100895 ; NCET-10-0202
资助机构National Natural Science Foundation of China ; Program for New Century Excellent Talents in University
引用统计
被引频次:29[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63054
专题北京大学第三临床医学院_神经内科
北京大学第三临床医学院_骨科
作者单位1.Peking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China
2.Tsinghua Univ, Beijing Jishuitan Hosp, Dept Spine Surg, Beijing 100035, Peoples R China
3.Peking Univ, Hosp 3, Dept Orthoped, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Han, Xiaoguang,Yang, Ning,Cui, Yueyi,et al. Simvastatin mobilizes bone marrow stromal cells migrating to injured areas and promotes functional recovery after spinal cord injury in the rat[J]. NEUROSCIENCE LETTERS,2012,521(2):136-141.
APA Han, Xiaoguang,Yang, Ning,Cui, Yueyi,Xu, Yingsheng,Dang, Gengting,&Song, Chunli.(2012).Simvastatin mobilizes bone marrow stromal cells migrating to injured areas and promotes functional recovery after spinal cord injury in the rat.NEUROSCIENCE LETTERS,521(2),136-141.
MLA Han, Xiaoguang,et al."Simvastatin mobilizes bone marrow stromal cells migrating to injured areas and promotes functional recovery after spinal cord injury in the rat".NEUROSCIENCE LETTERS 521.2(2012):136-141.
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