Behavioral and cellular determinants of treadmill training and recovery after SCI

为改善脊髓损伤患者的康复，在康复干预措施的设计和实施方面取得进展 都是需要的。确定阻碍运动训练益处的细胞和分子因素是一种 重要的第一步。了解这些因素如何影响何时应该开始康复也是 未知。因此，使用实验性脊髓损伤模型，这项建议将探索炎症在 远离脊髓损伤有组织运动的脊髓区域。技能培训的最佳窗口 可由这些炎症机制定义(目标1)。我们将使用下坡跑步机训练，因为它更多 比标准的平板跑步机训练更具挑战性。通过在不同的阶段开始下坡训练 炎症，我们将衡量哪个阶段的训练恢复更多的运动恢复。此外，我们还将 确定以活动为基础的训练是否推动髓鞘沿备用轴突的变化并改善功能(目标2)。 这些创新研究使用了新的转基因技术以及与临床相关的核磁共振方法。 最后，我们将探讨脊髓炎症易感性的地区差异(目标3)。 我们可以确定具有高训练诱导恢复潜力的脊髓区域。开发新类型的 专门针对这些有利于康复的地区的培训也可能促进功能恢复。建议进行的研究 对人类SCI有翻译潜力。

To improve recovery for individuals with SCI, gains in design and implementation of rehabilitation interventions are needed. Identifying cellular and molecular factors that impede the benefits of exercise training is an important first step. Understanding how these factors impact when rehabilitation should be initiated is also unknown. Therefore, using experimental SCI models, this proposal will explore the role of inflammation in spinal cord regions well-away from the SCI where movement is organized. The optimal window for skill training may be defined by these inflammatory mechanisms (Aim 1). We will use downhill treadmill training as it is more challenging than standard flat treadmill training. By initiating downhill training at different stages of inflammation, we will measure which stage training restores more locomotor recovery. Additionally, we will determine if activity-based training drives myelin changes along spared axons and improves function (Aim 2). These innovative studies use new transgenic technologies alongside clinically-relevant MRI approaches. Lastly, we will explore the regional differences in susceptibility to inflammation across the spinal cord (Aim 3). We may identify cord regions with high potential for training-induced recovery. Developing new types of training specifically for these pro-recovery regions may also boost functional recovery. The proposed studies have translational potential for human SCI.