Open AccessBone Marrow Stromal Cells Enhance Inter- and Intracortical Axonal Connections after Ischemic Stroke in Adult Rats
Author(s) -
Zhongwu Liu,
Yang Li,
Zheng Gang Zhang,
Xu Cui,
Yisheng Cui,
Mei Lü,
Smita Savant-Bhonsale,
Michael Chopp
Publication year - 2010
Publication title -
journal of cerebral blood flow and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.167
H-Index - 193
eISSN - 1559-7016
pISSN - 0271-678X
DOI - 10.1038/jcbfm.2010.8
Subject(s) - forelimb , motor cortex , corpus callosum , biotinylated dextran amine , medicine , neuroplasticity , stroke (engine) , sprouting , cerebral cortex , neuroscience , stromal cell , bone marrow , anatomy , axon , pathology , biology , mechanical engineering , botany , stimulation , engineering
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.