SPARING AND EXERCISE TRAINING PROMOTE RECOVERY IN SCI

随着医学治疗的进步，脊髓损伤（SCI）患者的功能运动恢复是一种现实的可能性。然而，促进运动功能改善的神经机制尚不清楚。了解病变严重程度、下行系统保留和运动恢复之间的相互关系至关重要。虽然更大的轴突保留会导致更强的恢复，但具体的下行系统的贡献仍然未知。此外，最近的证据表明，节约和恢复之间的关系可能不是线性的。如果存在非线性关系，则只需要轴突保留的微小修复性改变就可以产生实质性的行为改善。因此，我们建议使用临床相关的脊髓损伤动物模型来确定与运动恢复相关的特定下行神经底物。为了最终确定特定下降系统的敏感性和非线性恢复模式的存在，我们将对挫伤严重程度进行系统分级，并检查运动恢复的选定感觉和运动成分。此外，我们将确定分布于多个核的轴突保留是否比孤立于一个或两个特定核的轴突保留更能诱导运动恢复。我们将比较挫伤后的分布式保留和选择性索切断术的特定保留所带来的运动恢复。我们还将确定持久改善脊髓损伤后运动训练引起的地上运动所需的神经解剖学成分。任何康复的关键特征是运动引起的相关功能条件的改善的延续。我们将确定将训练从跑步机转移到地上运动所需的备用下行轴突的来源和数量。尤其重要的是了解与跑步机运动相关的训练转移，以便新的治疗干预针对促进实质性功能恢复最关键的神经系统。

Functional locomotor recovery in patients with spinal cord injury (SCI) is a realistic possibility given advancements in medical treatment; however, the neural mechanisms that subserve improved motor function are poorly understood. Understanding the interrelationship between lesion severity, sparing of descending systems and locomotor recovery is critical. While greater axonal sparing results in enhanced recovery, the contribution of specific descending systems remains unknown. Furthermore, recent evidence suggests that the relationship between sparing and recovery may not be linear. Should a non-linear relationship exist, only small reparative changes in axon sparing would be needed to produce substantial behavioral improvement. Therefore, we propose to identify specific descending neural substrates associated with locomotor recovery using a clinically relevant animal model of SCI. To conclusively determine the susceptibility of specific descending systems and the existence of a non-linear recovery pattern, we will produce systematic gradations, in contusion severity and examine selected sensory and motor components of locomotor recovery. In addition, we will determine whether axonal sparing distributed throughout multiple nuclei will induce greater locomotor recovery than sparing isolated to one or two specific nuclei. We will compare the motor recovery resulting from distributed sparing following contusion injury to specific sparing from selective funiculotomies. We will also identify the neuroanatomical components needed to produce lasting improvements in over-ground locomotion induced by exercise training after SCI. The critical feature of any rehabilitation is the carry-over of exercise-induced improvements to functionally relevant conditions. We will determine the source and amount of spared descending axons necessary to produce transfer of training from treadmill to over-ground locomotion. It is especially important to understand the transfer of training associated with treadmill locomotion so that new therapeutic interventions target the neural systems most critical for promoting substantial functional recovery.