Mechanisms of locomotor recovery after SCI in cats

神经生长促进因子脊髓内移植促进脊髓损伤修复 脊髓损伤动物模型中的运动功能。我们怀疑，这种复苏可能主要是由于 这些因素对负责跑台牵引性运动的脊髓回路的影响 可以在带刺的动物和人类身上观察到。我们的长期目标是最大限度地利用 脊髓损伤后使用联合疗法结合再生性移植物可获得恢复， 感觉运动训练，以及腰椎运动回路的电刺激。这个项目的目标是 目的是确定：1)是否需要从脊髓上中枢生长才能获得运动恢复 通过移植生长因子提供，2)腰椎运动回路能否被激活 通过亚慢性或慢性损伤模型的移植，以及3)脊柱移植的效果 对运动回路的作用与通过运动训练获得的效果相似。在AIMS中 1和2，将评估神经营养因子产生细胞移植所提供的运动恢复 通过运动学分析在哺乳动物脊髓损伤和神经损伤模型中的跑步机运动 生长将使用组织学方法进行测量。目标一号将使用一种不透膜来阻止 脊髓上轴突通过损伤生长的可能性。在目标2中，嫁接将在延迟2或 脊椎横断术后6周。在目标3中，将评估对脊椎电路的修改 通过刺激接受神经营养因子产生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计算模型 运动神经回路与后肢肌肉骨骼模型相结合。 该项目的结果将提供对脊柱机制负责的重要洞察 控制运动并将构成朝着制定有效方法迈出的重要一步 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.