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的广泛变化。然而，尚不清楚脊髓损伤后发生的解剖重组的确切性质和程度尚未得到充分了解。单侧中枢神经系统损伤后，受损途径的再生和未损坏区域的解剖重组都可能发生，并有助于功能的恢复。我们假设在治疗后的功能恢复以增加成年大鼠脊髓损伤后轴突生长，这不仅是由于检查期轴突的再生，而且还归因于SCI上方的神经元回路的重组。我们还假设，药理干预措施增加了生长的内在神经元能力和特定的康复策略以协同提高神经解剖学可塑性和功能恢复。提出的研究将在C3/C4（CHX）处使用宫颈脊髓过度裂口。这种病变使我们能够在未损坏的途径中直接和完全损坏的途径中的可塑性进行比较。我们的研究表明，直接损坏的途径的再生和挽救途径的重组都有助于恢复功能。该模型还允许我们检查熟练的前肢功能和运动的恢复。提出的研究将研究特定药理干预对增加神经内营地的影响和康复策略，以增加对神经解剖学可塑性和功能恢复的活动的影响。受伤后（急性），2周延迟（亚急性）和3个月延迟（慢性）后，将立即采用干预措施。我们将使用定量的神经解剖学和行为技术以及最新的功能成像方法来纵向遵循神经解剖学和功能重组，并定义特定重塑对观察到的功能恢复的贡献。我们将定义发生在代表性的脊柱上和脊柱区域内的解剖重组。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了解受伤中枢神经系统内发生的变化，以及它们如何受到调节，并且在康复策略中至关重要，以增加脊髓损伤后神经可塑性和功能恢复。