Bone marrow stromal cells enhance inter- and intracortical axonal connections after ischemic stroke in adult rats.

Bone marrow stromal cells enhance inter- and intracortical axonal connections after ischemic stroke in adult rats.
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DOI:
10.1038/jcbfm.2010.8
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发表时间:
2010-07
期刊:
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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其他
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我们研究了单侧中风和骨髓基质细胞(BMSC)治疗后大鼠双侧运动皮质的轴突可塑性。将大鼠永久性右侧大脑中动脉闭塞,1天后静脉内给予磷酸盐缓冲盐水或BMSC。每周进行一次粘合剂清除试验和改良的神经系统严重程度评分,以监测肢体功能缺损和恢复情况。将生物素化葡聚糖胺注射到右侧运动皮质中进行顺行追踪,以评估对侧运动皮质和同侧前肢吻侧区域的轴突发芽。中风后28天处死动物。骨髓间充质干细胞显著促进了渐进性功能恢复。与正常动物相比,脑卒中后对侧运动皮层和同侧前肢吻侧区的轴突密度均显著增加。骨髓基质细胞显着增强这种半球间和皮质内的连接。然而,胼胝体中标记的经胼胝体轴突没有改变中风或治疗。大脑半球间和皮质内轴突发芽与卒中后的行为结果显著且高度相关。这项研究表明,中风后,在梗死周围运动皮质中存活的皮质神经元经历轴突发芽以恢复不同大脑区域之间的连接。骨髓基质细胞增强轴突可塑性,这可能是神经功能改善的基础。
We investigated axonal plasticity in the bilateral motor cortices in rats after unilateral stroke and bone marrow stromal cell (BMSC) treatment. Rats were subjected to permanent right middle cerebral artery occlusion followed by intravenous administration of phosphate-buffered saline or BMSCs 1 day later. Adhesive-removal test and modified neurologic severity score were performed weekly to monitor limb functional deficit and recovery. Anterograde tracing with biotinylated dextran amine injected into the right motor cortex was used to assess axonal sprouting in the contralateral motor cortex and ipsilateral rostral forelimb area. Animals were killed 28 days after stroke. Progressive functional recovery was significantly enhanced by BMSCs. Compared with normal animals, axonal density in both contralateral motor cortex and ipsilateral rostral forelimb area significantly increased after stroke. Bone marrow stromal cells markedly enhanced such interhemispheric and intracortical connections. However, labeled transcallosal axons in the corpus callosum were not altered with either stroke or treatment. Both interhemispheric and intracortical axonal sprouting were significantly and highly correlated with behavioral outcome after stroke. This study suggests that, after stroke, cortical neurons surviving in the peri-infarct motor cortex undergo axonal sprouting to restore connections between different cerebral areas. Bone marrow stromal cells enhance axonal plasticity, which may underlie neurologic functional improvement.
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