中枢模式发生器（centrol pattern generator，CPG）是脊髓损伤后步行功能恢复的基础，它受皮层感觉运动区、脑干运动网络调控。项目前期研究显示：1）康复训练增强脊髓动物CPG可塑性：谷氨酸能、去甲肾上腺素能、多巴胺能神经元可塑性增强，CPG代谢增高；2）脊髓损伤患者感觉运动皮层可塑性与运动功能恢复相关。结合文献报道我们认为：脊髓损伤后，脑干运动网络可塑性发生改变，康复治疗可能通过皮层感觉运动区--脑干运动网络--网状脊髓束途径调控CPG，促进运动功能恢复。为验证此假设，我们拟取脊髓损伤患者，对其进行减重步行训练干预，利用多模态核磁技术观察脑干运动网络可塑性, 为进一步研究、优化或开发临床康复策略提供依据.

Locomotion recovery in patients with spinal cord injury(SCI) is based on spinal cord centrol pattern generator(CPG). And CPG depend on the regulation of supraspinal cord structures. However, the plasticity of supraspinal cord structures is not clear. The results of our pilot studies demonstrated that the damaged axon of corticospinal tract can’t regeneration, wherera the number and distribution of oradrenergic, erotoninergic, ordopaminergic neuron of CPG changed in rats with spinal cord contused. In addition, the plasticity of primary sensorimotor cortex was changed and positively correlated with the total American Spinal Injury Association motor score in patients with SCI. Based on these results and other reports, we hypothesize that defined brainstem motor networks present anatomical plasticity in SCI patients, and rehabilitation therapy contributes to functional recovery after injury by promoting the plasticity of sensorimotor cortex- brainstem motor networks- the reticulospinal tract-CPG circuits. In order to clarify the hypothesis, the SCI patients will perform body weight-support-treadmill training, and the multi-parameter MRI will be carried out to observe the anatomical and functional plasticity of brainstem motor networks, and the circuits of sensorimotor cortex- brainstem motor networks- the reticulospinal tract-CPG. These results will also be confirmed by the clinical function assessment, electrophysiological feature and neurotransmitter analysis. Meanwhile，We will also use the Positron emission tomography -Computed Tomography （PET-CT）,immunechemistry, west-blotting to observe the underlined mechanism of plasicity of brainstem motor networks, circuits of sensorimotor cortex- brainstem motor networks- the reticulospinal tract for rats with spinal cord injury. We aim to determine the plasticity of supraspinal cord structures and its regulation on CPG, and to provide new insights for SCI clinical rehabilitation.

项目背景：中枢模式发生器（centrol pattern generator，CPG）是脊髓损伤后步行功能恢复的基础，它受皮层感觉运动区、脑干运动网络调控；项目前期研究显示：康复训练增强脊髓动物CPG可塑性：谷氨酸能、去甲肾上腺素能、多巴胺能神经元可塑性增强，CPG代谢增高；结合文献报道我们认为：脊髓损伤后，脑干运动网络可塑性发生改变，康复治疗可能通过皮层感觉运动区-脑干运动网络-网状脊髓束途径调控CPG促进运动功能恢复。为验证此假设，我们分别取脊髓大鼠和脊髓损伤患者，对其进行减重步行训练干预，分别利用组织学和多模态核磁技术观察脑干运动网络可塑性 , 研究内容： 1、减重步行训练对不完全脊髓损伤大鼠中脑脚桥核和延髓巨细胞网状核可塑性的影响：大鼠分为减重步行训练组、未训练组和假手术组，采用PET-CT、组织学、免疫化学及BBB评分观察减重步行训练对不完全脊髓损伤大鼠中脑运动区脚桥核和延髓巨细胞网状核可塑性和后肢运动功能的影响。2、利用VBM技术观察脊髓损伤患者皮层运动中枢、脑干运动网络可塑性的动态变化。目前已完成第一部分研究，第二部分研究仅完成了3例患者，正在进行收集病例中。 研究结果：1、各组大鼠脚桥核和巨细胞网状核的NeuN+神经元数量无差异（P＞0.05），但训练组脚桥核和巨细胞网状核2型囊泡谷氨酸转运体的积分光密度值较未训练组明显增强（P＜0.01）； 2、训练组中脑脚桥核和延髓巨细胞网状核18F-氟脱氧葡萄糖的标准摄取值、延髓巨细胞网状核神经元数量较对照组呈增高趋势，但三组间差异无统计学意义（P＞0.05）. 3、训练组大鼠BBB评分在造模后4周、 7周均较未训练组高（P＜ 0.05），且BBB评分与中脑脚桥核和延髓巨细胞网状核2型囊泡谷氨酸转运体的积分光密度值成正相关。科学意义：上述结果提示：减重步行训练可促进脊髓大鼠运动功能恢复，其机制与提高脊髓大鼠中脑脚桥核和延髓巨细胞网状核谷氨酸能信号传递有关。