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Behavioral and cellular determinants of treadmill training and recovery after SCI

SCI 后跑步机训练和恢复的行为和细胞决定因素

基本信息

批准号：
9340300
负责人：
D M Basso
金额：
$ 33.14万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9340300
关键词：
3-Dimensional Animals Automobile Driving Axon Behavioral Biological Markers Blood Bone Marrow Brain Brain region CCL2 gene Cell Differentiation process Cell Lineage Cervical Chest Clinic Contusions Data Development Environment Exercise Failure Forelimb Genes Glutamates Histology Human Hypertrophy Image Impairment Individual Inflammation Inflammatory Injury Intervention Knockout Mice Knowledge Learning Lesion Location Locomotion Locomotor Recovery Magnetic Resonance Imaging Measures Mediator of activation protein Modeling Molecular Motor Skills Movement Mus Myelin Myeloid Cells Neuronal Plasticity Neurons Oligodendroglia Outcome Peripheral Phase Physiological Predisposition Production Recovery Recovery of Function Recruitment Activity Regulator Genes Rehabilitation therapy Relaxation Resolution Rodent Role Site Specificity Spinal Cord Spinal Cord Contusions Spinal cord injury Spottings Technology Testing Therapeutic Therapeutic exercise Time Tissues Training Transgenic Mice Transgenic Organisms base central pattern generator chemokine clinically relevant cytokine design exercise training experimental study improved improved functioning in vivo innovation kinematics migration monocyte motor learning motor recovery myelination oligodendrocyte lineage oligodendrocyte precursor permissiveness precursor cell prevent regional difference relating to nervous system response skills training trafficking translational approach treadmill training white matter

项目摘要

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.

改善SCI患者的康复，康复干预措施的设计和实施是必要的。识别阻碍运动训练益处的细胞和分子因素是一项重要的研究。重要的第一步。了解这些因素如何影响何时应该开始康复，未知因此，使用实验性SCI模型，本建议将探讨炎症在远离SCI的脊髓区域，运动在那里组织起来。技能培训的最佳窗口可能由这些炎症机制定义（目的1）。我们将使用下坡跑步机训练，因为它是更多比标准的平板跑步机训练更具挑战性。通过在不同阶段开始下坡训练，炎症，我们将测量哪个阶段的训练可以恢复更多的运动恢复。此外，我们将确定基于活动的训练是否会沿着备用轴突驱动髓鞘变化并改善功能（目标2）。这些创新的研究使用了新的转基因技术以及临床相关的MRI方法。最后，我们将探讨脊髓炎症易感性的区域差异（目的3）。我们可以确定具有高潜力的训练诱导恢复的脊髓区域。发展新型专门针对这些促恢复区域的训练也可以促进功能恢复。拟议的研究对人类脊髓损伤有转化潜力。