Mechanisms of locomotor recovery after SCI in cats

神经生长促进因子在损伤脊髓内的移植促进了脊髓损伤的恢复， 脊髓损伤动物模型的运动。我们怀疑这种复苏可能主要是由于 这些因素对负责跑步机运动的脊髓回路的影响， 可以在脊椎动物和人类中观察到。我们的长期目标是最大限度地提高 使用结合再生移植物的组合疗法可在脊髓损伤后获得恢复， 感觉运动训练和腰部运动回路的电刺激。本项目的目的是 目的是确定：1）从脊髓上中枢生长是否是获得运动恢复所必需的 2）是否可以激活腰椎运动回路 通过亚慢性或慢性损伤模型中的移植，以及3）脊柱移植的影响是否 在运动回路上的作用类似于运动训练所获得的效果。目标 如图1和2所示，将评估由神经营养素产生细胞的移植提供的运动恢复 通过在脊髓损伤的哺乳动物模型中跑步机运动的运动学分析， 使用组织学方法测量生长。Aim 1将使用不渗透膜来阻挡 脊髓上轴突通过损伤生长的可能性。在目标2中，移植将在延迟2或 脊髓横断后6周。在目标3中，将评价脊髓回路的修改 通过刺激接受神经营养素的动物组中选定的传入通路， 移植或运动训练，并使用最近引入的哺乳动物的计算模型， 运动神经回路与后肢的肌肉骨骼模型相结合。 该项目的结果将提供重要的洞察脊柱机制负责 控制运动，并将构成发展有效方法的重要一步 用于脊髓损伤后运动功能的恢复。

Transplants of nerve growth promoting factors into the injured spinal cord promote the recovery of locomotion in animal models of spinal cord injury. We suspect that this recovery may be mostly due to the effects of those factors on the spinal cord circuitry responsible for the treadmill entrained locomotion that can be observed in spinalized animals and humans. Our long-term goals are to maximize the locomotor recovery obtainable after spinal cord injury using combination therapies combining regenerative grafts, sensorimotor training, and electrical stimulation of the lumbar locomotor circuitry. The aims of this project are to establish: 1) whether growth from supraspinal centers is necessary to obtain the locomotor recovery provided by transplant of the growth factors, 2) whether the lumbar circuitry of locomotion can be activated by transplants in a sub-chronic or chronic model of injury, and 3) whether the effects of spinal transplants on the locomotor circuitry are similar in their actions to the effects obtained with locomotor training. In Aims 1 & 2, the locomotor recovery provided by the transplant of neurotrophins producing cells will be evaluated via kinematic analyses of treadmill locomotion in a mammalian model of spinal cord injury, and nerve growth will be measured using histological methods. Aim 1 will use an impermeable membrane to block the possibility of supraspinal axonal growth through the injury. In Aim 2, grafting will occur after a delay of 2 or 6 weeks following the spinal transection. In Aim 3, the modifications to the spinal circuitry will be evaluated via stimulation of selected afferent pathways in groups of animals receiving the neurotrophins producing transplants or locomotor training, and using a recently introduced computational model of the mammalian locomotor neural circuitry combined with a musculo-skeletal model of the hindlimbs. The results of this project will provide significant insight into the spinal mechanisms responsible for the control of locomotion and will constitute an important step towards the development of effective methods for the restoration of locomotor function after spinal cord injury.