Contralesional axonal remodeling of the corticospinal system in adult rats after stroke and bone marrow stromal cell treatment.
Contralesional axonal remodeling of the corticospinal system in adult rats after stroke and bone marrow stromal cell treatment.
复制标题
DOI：
10.1161/strokeaha.107.511659
复制
发表时间：
2008-09
期刊：
影响因子：
8.3
通讯作者：
Chopp M
中科院分区：
文献类型：
--
作者：
Liu Z;Li Y;Zhang X;Savant-Bhonsale S;Chopp M
脑卒中后运动功能恢复与双侧半球神经元重组有关。我们研究了脑卒中和骨髓基质细胞治疗后大鼠脑和脊髓中对侧皮质脊髓束的重塑。成年雄性Wistar大鼠进行永久性右侧大脑中动脉闭塞。缺血后1天，将磷酸盐缓冲盐水或骨髓基质细胞注射到尾静脉中。每周进行一次粘合剂清除试验，以监测功能恢复情况。脑卒中后6周，测量左侧运动皮层微刺激诱发双侧前肢运动的阈值电流。当皮质内微刺激完成后，生物素化葡聚糖胺被注射到左侧运动皮质顺行标记皮质脊髓束。在安乐死前4天，将伪狂犬病病毒-152-EGFP和614-mRFP分别注射到左或右前肢伸肌中。所有动物在中风后8周被安乐死。在正常大鼠（n=5），皮质脊髓束呈单侧神经支配模式。在大脑中动脉闭塞大鼠（n=8）中，我们的数据表明：1）中风降低了引起同侧前肢运动的刺激阈值; 2）EGFP阳性锥体神经元在左侧完整皮质中增加，其标记自左侧中风受损的前肢; 3）生物素化葡聚糖胺标记的对侧损伤轴突发芽到失神经脊髓中。骨髓基质细胞显著增强上述3种反应（n=8，P<0.05）。我们的数据表明，皮质脊髓束纤维起源于对侧运动皮质发芽到失神经脊髓中风和骨髓基质细胞治疗后，这可能有助于功能恢复。
Motor recovery after stroke is associated with neuronal reorganization in bilateral hemispheres. We investigated contralesional corticospinal tract remodeling in the brain and spinal cord in rats after stroke and treatment of bone marrow stromal cells. Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion. Phosphate-buffered saline or bone marrow stromal cells were injected into a tail vein 1 day postischemia. An adhesive removal test was performed weekly to monitor functional recovery. Threshold currents of intracortical microstimulation on the left motor cortex for evoking bilateral forelimb movements were measured 6 weeks after stroke. When intracortical microstimulation was completed, biotinylated dextran amine was injected into the left motor cortex to anterogradely label the corticospinal tract. At 4 days before euthanization, pseudorabies virus-152-EGFP and 614-mRFP were injected into left or right forelimb extensor muscles, respectively. All animals were euthanized 8 weeks after stroke. In normal rats (n=5), the corticospinal tract showed a unilateral innervation pattern. In middle cerebral artery occlusion rats (n=8), our data demonstrated that: 1) stroke reduced the stimulation threshold evoking ipsilateral forelimb movement; 2) EGFP-positive pyramidal neurons were increased in the left intact cortex, which were labeled from the left stroke-impaired forelimb; and 3) biotinylated dextran amine-labeled contralesional axons sprouted into the denervated spinal cord. Bone marrow stromal cells significantly enhanced all 3 responses (n=8, P<0.05). Our data demonstrated that corticospinal tract fibers originating from the contralesional motor cortex sprout into the denervated spinal cord after stroke and bone marrow stromal cells treatment, which may contribute to functional recovery.