Shen L H, Li Y, Chen J, Zhang J, Vanguri P, Borneman J, Chopp M
Department of Neurology, Henry Ford Health Sciences Center, E&R 3056, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Neuroscience. 2006;137(2):393-9. doi: 10.1016/j.neuroscience.2005.08.092. Epub 2005 Nov 17.
The present study investigates the induction of axon and myelin remodeling as a possible mechanism by which treatment of stroke with bone marrow stromal cells improves neurological functional recovery. Adult male Wistar rats were subjected to 2 h of middle cerebral artery occlusion, followed by an injection of 2 x 10(6) rat bone marrow stromal cells or phosphate-buffered saline into the internal carotid artery 24 h later. Animals were killed at 28 days after stroke. Functional tests, histo- and immunohistochemical staining were performed. Significant functional recovery was found after bone marrow stromal cell administration in all the three tests performed (modified neurological severity score, adhesive-removal and corner tests). Bone marrow stromal cell treatment markedly increased vessel sprouting, synaptophysin expression and NG2 positive cell numbers and density in the cortical peri-infarct area. In bone marrow stromal cell-treated rats, the number of Ki-67 positive proliferating cells and oligodendrocyte precursor cells in the corpus callosum increased significantly in concert with the enhancement of the areas of the corpus callosum in both hemispheres. These results suggest that bone marrow stromal cells facilitate axonal sprouting and remyelination in the cortical ischemic boundary zone and corpus callosum, which may underlie neurological functional improvement caused by bone marrow stromal cell treatment.
本研究探讨轴突和髓鞘重塑的诱导作用,作为骨髓基质细胞治疗中风改善神经功能恢复的一种可能机制。成年雄性Wistar大鼠接受2小时的大脑中动脉闭塞,随后在24小时后经颈内动脉注射2×10⁶大鼠骨髓基质细胞或磷酸盐缓冲盐水。在中风后28天处死动物。进行功能测试、组织学和免疫组织化学染色。在进行的所有三项测试(改良神经功能缺损评分、粘胶去除和转角测试)中,给予骨髓基质细胞后均发现显著的功能恢复。骨髓基质细胞治疗显著增加了皮质梗死周边区域的血管生成、突触素表达以及NG2阳性细胞数量和密度。在接受骨髓基质细胞治疗的大鼠中,胼胝体中Ki-67阳性增殖细胞和少突胶质前体细胞的数量显著增加,同时两个半球胼胝体的面积也增大。这些结果表明,骨髓基质细胞促进皮质缺血边界区和胼胝体中的轴突发芽和髓鞘再生,这可能是骨髓基质细胞治疗引起神经功能改善的基础。