Optimizing functional recovery following cervical spinal cord injury

优化颈脊髓损伤后的功能恢复

• 批准号: 8910795
• 负责人: Michael Aron Lane
• 金额: $ 33.44万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8910795
• 关键词: Adult; Affect; Animals; Axon; Behavior; Cations; Cell Transplants; Cells; Cervical; Cervical spinal cord injury; Chronic; Clinical; Contusions; Coupled; Development; Electrodes; Environmental air flow; Fiber; Functional disorder; Goals; Hour; Implant; Incidence; Injury; Interneurons; Lead; Light; Lower Extremity; Measures; Methods; Modeling; Morbidity - disease rate; Motor; Motor Neurons; Movement; Muscle; Neurological outcome; Neurons; Neurotransmitters; Outcome; Output; Paralysed; Pathway interactions; Phenotype; Phrenic Motor System; Plethysmography; Population; Principal Investigator; Procedures; Rattus; Recovery; Recovery of Function; Relative (related person); Research; Respiration; Respiratory Diaphragm; Rhodopsin; Side; Site; Spinal; Spinal Cord; Spinal Cord Contusions; Spinal cord injury; Structure of phrenic nerve; Suspension substance; Suspensions; Synapses; System; Technology; Testing; Therapeutic; Time; Tissues; Transgenic Organisms; Transplantation; Upper Extremity; Viral; axon growth; clinically relevant; disability; experience; fetal; functional improvement; functional plasticity; immunocytochemistry; improved; indexing; injured; mortality; novel; optogenetics; progenitor; programs; relating to nervous system; repaired; research study; respiratory; spinal cord repair; stem; stem cell therapy; therapeutic target

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) results in the loss of many functions, of which motor disability is undoubtedly the more commonly recognized neurological outcome. Especially devastating are injuries that commonly occur in the cervical region of the spinal cord. At those levels SCI affects not only upper and lower extremity movements, but also impairs one of the more basic functions required for survival - namely, respiration. There is a high incidence of respiratory complications following cervical SCI, which can occur even when assisted ventilation is not required. Furthermore, respiratory dysfunction and associated secondary complications remain the leading cause of morbidity and mortality in people with cervical SCI. Particularly concerning is that the number of cervical SCIs has increased in recent years. Although optimal spinal cord repair has yet to be achieved, there is mounting experimental and clinical evidence for some spontaneous functional recovery - or "plasticity" - over time post-injury. However, the extent of improvement that can be attributed to plasticity remains limited. Results from our recent experiments have demonstrated that transplantation of stem-like cells at the site of injury can enhance anatomical repair and improve diaphragm function following clinically-relevant cervical SCI. The diaphragm is regarded as the primary muscle of respiration. The experiments proposed here build upon our extensive experience with respiratory outcomes following cervical SCI, and will test whether maturing donor nerve cells can anatomically and functionally integrate with spinal circuits responsible for diaphragm activity. These experiments will also employ a novel "optogenetic" approach to control the activity of transplanted cells and test whether the functionality can be enhanced between donor neurons and the injured host spinal cord. Not only will these experiments test a promising treatment approach in an important and clinically relevant injury model, but they will significantl improve our understanding of the therapeutic potential of a wide range of neuronal transplantation approaches, including many of the stem cell therapies currently being tested experimentally and clinically.

描述（由申请人提供）：脊髓损伤（SCI）导致许多功能的丧失，其中运动障碍无疑是更常见的神经系统结果。尤其是毁灭性的是通常在脊髓的宫颈区域发生的伤害。在这些水平下，SCI不仅会影响上肢和下肢运动，而且会损害生存所需的更基本的功能之一，即呼吸。宫颈SCI后，呼吸并发症发生率很高，即使不需要辅助通风，也可能发生。此外，宫颈科学患者的呼吸功能障碍和相关的次要并发症仍然是发病率和死亡率的主要原因。特别是关于宫颈SCI的数量近年来有所增加。尽管尚未实现最佳的脊髓修复，但随着时间的流逝，有一些自发的功能恢复（或“可塑性”）的实验和临床证据。但是，可以归因于可塑性的改进程度仍然有限​​。我们最近的实验的结果表明，在损伤部位对茎样细胞的移植可以增强解剖学修复，并改善临床上与宫颈SCI相关后的隔膜功能。隔膜被视为呼吸的主要肌肉。这里提出的实验基于我们在宫颈SCI后具有呼吸结局的丰富经验，并将测试成熟的供体神经细胞是否可以在解剖和功能上与负责隔膜活性的脊柱回路进行整合。这些实验还将采用一种新型的“光遗传学”方法来控制移植细胞的活性，并测试是否可以在供体神经元和受伤的宿主脊髓之间增强功能。这些实验不仅会在重要且与临床相关的损伤模型中检验有前途的治疗方法，而且它们将大大提高我们对广泛神经元移植方法的治疗潜力的理解，包括当前正在实验和临床上测试的许多干细胞疗法。