Spinal cord injury: plasticity and recovery of function

脊髓损伤：可塑性和功能恢复

• 批准号: 7541743
• 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/7541743
• 关键词: Acute; Adult; Aftercare; Arts; Behavioral; Cervical spinal cord injury; Cervical spinal cord structure; Chronic; Complement 3a; Cyclic AMP; Environment; Equilibrium; Forelimb; Functional Imaging; Growth; Injury; Intervention; Lead; Lesion; Locomotion; 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; axon growth; axon regeneration; base; defined contribution; dorsal column; imaging modality; improved functioning; in vivo; injured; intervention effect; 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广泛变化。精确的性质和 然而，脊髓损伤后发生的解剖重组的程度及其调节方式， 没有被很好地理解。我们最近的研究表明，增加神经元 cAMP 和 那些增加受伤后活动的物质可以独立地促进解剖可塑性和功能 脊髓损伤后的恢复。我们假设治疗后功能恢复会增加 成年大鼠脊髓损伤后的轴突生长不仅是由于脊髓上轴突再生，而且 也是由于 SCI 上方神经元回路的重组所致。我们还假设 药物干预以增加内在神经元的生长和特定康复能力 增加活动的策略协同作用以增加神经解剖学可塑性和功能 恢复。拟议的研究将在成年大鼠的 C3/C4 (CHX) 处使用颈脊髓过度半切。这 损伤使我们能够将直接和完全受损的通路的可塑性与重塑进行比较 未损坏的路径。我们的研究表明，通路的再生既直接受损，又 空闲通路的重组有助于功能的恢复。这个模型还允许我们 检查熟练的前肢功能和运动的恢复情况。拟议的研究将审查 特定药物干预增加神经元内 cAMP 的效果和康复策略 增加神经解剖可塑性和功能恢复的活动。将采取干预措施 受伤后立即（急性）、延迟 2 周后（亚急性）和延迟 3 个月后（慢性）。我们将 使用定量神经解剖学和行为技术以及最先进的功能成像方法 受伤后纵向跟踪解剖和功能重组，并定义 观察到功能恢复的特定重塑。我们将检查解剖学的范围 典型的脊髓上和脊髓区域内发生的组织：感觉运动皮层和红色 核（与熟练运动相关的脊髓上通路），中缝脊髓神经元（一条通路） 与运动相关）、背柱系统（上升感觉通路）和脊髓 本体脊髓和运动神经元的头端和尾端到病变（与平衡相关的节段通路） 和协调）。我们还将定义运动功能恢复的时间过程和程度。 这里概述的实验将有助于更好地理解内部发生的变化 受伤的中枢神经系统以及它们如何受到监管，并且在康复策略中非常重要，以增加 脊髓损伤后的神经可塑性和功能恢复。