Mechanisms of Locomotor Recovery after SCI in Cats

猫脊髓损伤后运动恢复的机制

• 批准号: 8652511
• 负责人: Michel A Lemay
• 金额: $ 25.98万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-15 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8652511
• 关键词: Acute; Adult; Affect; Afferent Pathways; Animal Model; Animals; Ankle; Autologous; Axon; Back; Biopsy; Body Weight; Brain-Derived Neurotrophic Factor; Cell Survival; Cells; Chest; Chronic; Clinic; Clinical; Computer Simulation; Cutaneous; Evaluation; Felis catus; Fibroblasts; Immunosuppression; Implant; Injection of therapeutic agent; Injury; Instruction; Interneurons; Laboratories; Lateral; Leg; Lesion; Locomotion; Locomotor Recovery; Locomotor training; Lumbar spinal cord structure; Measures; Mediating; Methodology; Methods; Mission; Modality; Modeling; Motor Neurons; Muscle; National Institute of Neurological Disorders and Stroke; Natural regeneration; Operative Surgical Procedures; Outcome Measure; Pathway interactions; Patients; Pattern; Preparation; Recovery; Relative (related person); Research Personnel; Sensory; Site; Skin; Spinal; Spinal Cord; Spinal Puncture; Spinal cord injury; Synapses; System; Techniques; Testing; Therapeutic; Time; Training; Training Support; Translations; Transplant Recipients; Transplantation; Weight-Bearing state; Work; Xenograft procedure; axon growth; base; foot; in vivo; injured; insight; medial plantar nerve; minimal risk; nervous system disorder; neuromechanism; neuromuscular; neuromusculoskeletal; neurotrophic factor; novel; repaired; response; spinal nerve posterior root; sural nerve; transmission process; treadmill training

Delivery of neurotrophins to the spinal cord is a promising technique to re-engage the locomotor circuitry following spinal cord injury and their use may augment the recovery obtained with body-weight supported treadmill training. The mechanism by which neurotrophins promote locomotor recovery is unknown, but our modeling work suggests that plasticity in the afferent system transmission is involved in recovery. Aim 1 will obtain information about the changes in afferent transmission to motoneurons and interneurons following neurotrophin delivery to the spinal cord and compare those to the ones obtained with body-weight supported treadmill training. Acquiring this information will provide new insights into the neural mechanisms associated with recovery after SCI and serve as a novel outcome measure for new therapies. We propose to use intracellular and multiunit recording techniques to characterize and compare the changes in afferent transmission obtained with body-weight supported treadmill training or neurotrophin producing cellular transplants. In addition, we will characterize the interneuronal activity patterns and afferent effects on this activity following to thetiA/otreatment modalities. We hypothesize that afferent transmission to motoneurons and interneurons is modified by neurotrophin transplants in a manner similar to the way it is affected by body-weight supported treadmill training, but that the effects are more widespread in the neurotrophin treated animals due to a wider distribution of the neurotrophins with this methodology. In our second aim, we intend to refine our transplant technique to the point where neurotrophin producing transplants could be attempted in the clinic with minimal risks for the patient. We hypothesize that neurotrophins can be delivered via lumbar puncture injection of autologous cells modified to express neurotrophins and that these cells will promote the recovery of plantar weight-bearing stepping without the need for training in acutely and chronically injured animals.

将神经营养蛋白递送到脊髓是一种有前途的技术，可以重新引入运动电路 脊髓损伤和使用后可能会增加受支持的体重获得的恢复 跑步机训练。神经营养蛋白促进运动恢复的机制尚不清楚，但是我们 建模工作表明，传入系统传输中的可塑性涉及恢复。目标1意志 获取有关传入的传入变化运动神经元和中间神经元的信息 神经营养蛋白递送至脊髓，并将其与支撑的体重相比 跑步机训练。获取此信息将为相关的神经机制提供新的见解 在SCI后恢复，并作为新疗法的一种新型结果度量。我们建议使用 细胞内和多单元记录技术以表征和比较传入的变化 通过体重支撑的跑步机训练或神经营养蛋白产生细胞的传播 移植。此外，我们将表征对此的神经元活动模式和传入的影响 thetia/otreatment方式之后的活动。我们假设向运动神经元传播 神经营养蛋白移植以类似于其影响的方式来修饰神经元的神经元和中间神经元 体重支持的跑步机训练，但这种影响在神经营养素中更为普遍 通过这种方法，由于神经营养蛋白的分布更广泛而治疗的动物。在我们的第二个目标中，我们 打算将我们的移植技术完善到可能是神经营养蛋白的移植物的地步 试图在诊所中，患者的风险很小。我们假设可以传递神经营养蛋白 通过腰穿刺注射自体细胞，以表达神经营养蛋白，这些细胞将 促进足底体重踏上的恢复，而无需急性训练 长期受伤的动物。