Spinal cord injury: plasticity and recovery of function

脊髓损伤：可塑性和功能恢复

• 批准号: 7034911
• 负责人: BARBARA S BREGMAN
• 金额: $ 27.16万
• 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/7034911
• 关键词: injury; regeneration; rehabilitation; spinal cord injury

DESCRIPTION (provided by applicant): 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. After unilateral CNS injury, it is likely that both regeneration of damaged pathways and anatomical reorganization of undamaged regions occur and contribute to recovery of function. 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). 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 neuroanatomical and functional reorganization longitudinally after injury and to define the contribution of specific remodeling to the recovery of function observed. We will define the anatomical reorganization that occurs within representative supraspinal and spinal regions. 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 injured CNS and how they are regulated and will be important in rehabilitation strategies to increase neuroplasticity and functional recovery after spinal cord injury.

描述（由申请人提供）：脊髓损伤导致中枢神经系统广泛变化。然而，脊髓损伤后发生的解剖重组的确切性质和程度以及其调节方式尚不清楚。单侧中枢神经系统损伤后，受损通路的再生和未受损区域的解剖重组可能会发生，并有助于功能的恢复。我们假设成年大鼠脊髓损伤后进行增加轴突生长的治疗后功能的恢复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。我们还假设增加神经元内在生长能力的药物干预和增加活动的特定康复策略协同作用，以增加神经解剖可塑性和功能恢复。拟议的研究将在 C3/C4 (CHX) 处使用颈脊髓过度半切。这种损伤使我们能够将直接和完全受损的通路的可塑性与未受损的通路的重塑进行比较。我们的研究表明，直接受损途径的再生和幸存途径的重组都有助于功能的恢复。该模型还允许我们检查熟练的前肢功能以及运动的恢复情况。拟议的研究将检验特定药物干预对增加神经元内 cAMP 的影响，以及康复策略对增加神经解剖可塑性和功能恢复活动的影响。受伤后（急性）、延迟 2 周后（亚急性）和延迟 3 个月后（慢性）将立即采取干预措施。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来跟踪损伤后纵向的神经解剖学和功能重组，并确定特定重塑对观察到的功能恢复的贡献。我们将定义代表性的脊柱上和脊柱区域内发生的解剖重组。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受伤的中枢神经系统内发生的变化以及它们是如何调节的，并且对于增加脊髓损伤后的神经可塑性和功能恢复的康复策略非常重要。