Spinal cord injury: plasticity and recovery of function

脊髓损伤：可塑性和功能恢复

• 批准号: 7345392
• 负责人: BARBARA S BREGMAN
• 金额: $ 26.37万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7345392
• 关键词: Acute; Adult; Aftercare; Arts; Behavioral; Cervical spinal cord injury; Cervical spinal cord structure; Chronic; Complement 3a; Cyclic AMP; Effectiveness of Interventions; Elevation; Environment; Equilibrium; Forelimb; Functional Imaging; Growth; Injury; Intervention; Lead; Lesion; Locomotion; Methods; Modeling; Motor; Motor Activity; Motor Neurons; Movement; Natural regeneration; Nature; Neuraxis; Neuronal Plasticity; Neurons; Pathway interactions; Pattern; Pharmacological Treatment; Phosphodiesterase Inhibitors; Proteins; Rattus; Recovery; Recovery of Function; Red nucleus structure; Rehabilitation therapy; Research Personnel; Rolipram; Sensory; Site; Spinal; Spinal Cord; Spinal cord injury; Synapses; System; Techniques; Testing; Therapeutic; Time; Week; axon growth; axon regeneration; base; defined contribution; dorsal column; improved functioning; in vivo; injured; neuronal circuitry; programs; rehabilitation strategy; research study; spinal cord repair

Spinal cord injury results in widespread changes in the central nervous system. The precise nature and extent of the anatomical reorganization that occurs after spinal cord injury and how it is regulated, however, are not well understood. Our recent studies indicate that interventions that increase neuronal cAMP and those that increase post-injury activity can independently contribute to anatomical plasticity and functional recovery after spinal cord injury. We hypothesize that recovery of function after treatments to increase axonal growth following spinal cord injuries in adult rats is not only due to supraspinal axon regeneration but is also due to reorganization of the neuronal circuitry above the SCI. We also hypothesize that pharmacological interventions to increase the intrinsic neuronal capacity for growth and specific rehabilitative strategies to increase activity act synergistically to increase both neuroanatomical plasticity and functional recovery. Studies proposed will use cervical spinal cord over-hemisection at C3/C4 (CHX) in adult rats. This lesion allows us to compare plasticity in pathways damaged directly and completely with remodeling in undamaged pathways. Our studies indicate that both regeneration of pathways damaged directly and reorganization in spared pathways contribute to the recovery of function. This model also allows us to examine recovery of skilled forelimb function as well as locomotion. The studies proposed will examine the effects of specific pharmacological intervention to increase intraneuronal cAMP and rehabilitation strategies to increase activity on neuroanatomical plasticity and recovery of function. Interventions will be applied immediately after injury (acute), after a 2 week delay (sub-acute) and after a 3 month delay (chronic). We will use quantitative neuroanatomical and behavioral techniques and state-of-the-art functional imaging methods to follow anatomical and functional reorganization longitudinally after injury and to define the contribution of specific remodeling to the recovery of function observed. We will examine the extent of ananatomical ¿eorganization that occurs within representative supraspinal and spinal regions: sensorimotor cortex and red nucleus (supraspinal pathways associated with skilled movement), in raphespinal neurons (a pathway associated with locomotion), in the dorsal column system (ascending sensory pathway), and in spinal cord propriospinal and motor neurons rostral and caudal to lesion (segmental pathways associated with balance and coordination). We will also define the time course and extent of recovery of motor function that occurs. The experiments outlined here will lead to a better understanding of the changes that take place within the njured CNS and how they are regulated and will be important in rehabilitation strategies to increase neuroplasticity and functional recovery after spinal cord injury.

脊髓损伤导致中枢神经系统的宽度变化。精确性和 脊髓损伤后发生的解剖重组及其如何调节的程度 不太了解。我们最近的研究表明，增加神经元营地的干预措施 那些增加伤害后活动的人可以独立促进解剖学可塑性和功能 脊髓损伤后恢复。我们假设治疗后功能的恢复以增加 成年大鼠脊髓损伤后的轴突生长不仅是由于上轴突的再生，而且还引起 也是由于SCI上方的神经元电路的重组。我们还假设 药理学干预措施以提高内在神经元能力的生长和特定的康复能力 提高活动行为的策略协同化，以提高神经解剖学可塑性和功能性 恢复。提出的研究将在成年大鼠的C3/C4（CHX）处使用宫颈脊髓过度裂痕。这 病变使我们能够在直接而完全损坏的途径中比较重塑的可塑性 未损坏的途径。我们的研究表明，途径的再生直接受损，并且 宽松途径的重组有助于恢复功能。该模型还使我们能够 检查熟练的前肢功能和运动的恢复。提出的研究将检查 特定的药物干预措施增加神经内营地和康复策略的影响 增加对神经解剖学可塑性的活性和功能恢复。将采用干预措施 受伤后（急性），2周延迟（亚急性）和3个月延迟（慢性）后立即。我们将 使用定量的神经解剖学和行为技术以及最先进的功能成像方法 受伤后纵向遵循解剖和功能重组，并定义 特定的重塑，以恢复观察到的功能。我们将检查一系列的范围 �在代表性的脊柱上和脊柱区域内发生的质量组织：感觉运动皮层和红色 核（与熟练运动相关的上脊髓途径），在流浪神经元中（途径 与运动），背柱系统（上升感觉途径）和脊髓相关 周期性和运动神经元to骨和尾性病变（与平衡相关的节段性途径） 和协调）。我们还将定义发生的运动功能的恢复时间和恢复程度。 此处概述的实验将使人们更好地理解 nj uned的中枢神经系统及其如何受到监管，并且对于增加的康复策略将很重要 脊髓损伤后神经可塑性和功能恢复。