Mechanisms of Locomotor Recovery after SCI in Cats

将神经营养因子输送到脊髓是一种很有前途的重新启动运动回路的技术。 脊髓损伤后和使用它们可以促进在体重支持下的恢复 跑步机训练。神经营养因子促进运动恢复的机制尚不清楚，但我们的 模型工作表明，传入系统传递的可塑性参与了恢复。目标1将 获取有关运动神经元和中间神经元传入传递的变化的信息 神经营养因子向脊髓的传递，并与体重支持下的神经营养因子进行比较 跑步机训练。获得这些信息将提供对相关神经机制的新见解 与脊髓损伤后的恢复有关，并可作为新疗法的新结果衡量标准。我们建议使用 细胞内和多单位记录技术表征和比较传入的变化 通过体重支持的跑步机训练或神经营养因子产生细胞获得的传播 移植。此外，我们还将描述神经元间的活动模式和对此的传入效应。 根据tiA/o治疗模式开展的活动。我们假设传入运动神经元 而神经营养素移植对中间神经元的影响方式与其受影响的方式相似 体重支持的跑步机训练，但这种影响在神经营养因子中更为普遍 用这种方法治疗动物是因为神经营养因子的分布更广泛。在我们的第二个目标，我们 打算改进我们的移植技术，以使产生神经营养素的移植可以 在临床上尝试，对患者的风险最小。我们假设神经营养因子可以被输送 通过腰椎穿刺注射经修饰的表达神经营养因子的自体细胞，这些细胞将 促进足底负重步态的恢复，无需急诊训练 长期受伤的动物。

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.