Spinal cord injury: plasticity and recovery of function

脊髓损伤会导致中枢神经系统的广泛变化。精确的性质和 然而，脊髓损伤后发生的解剖重组的程度以及它是如何被调节的， 都没有被很好地理解。我们最近的研究表明，增加神经元cAMP和 那些增加损伤后活动的因素可以独立地促进解剖可塑性和功能 脊髓损伤后的康复。我们假设治疗后的功能恢复会增加 成年大鼠脊髓损伤后轴突的生长不仅源于脊髓上轴突的再生，而且 也是由于脊髓损伤上方神经元电路的重组所致。我们还假设 提高神经元生长和特定康复能力的药物干预 增加活性的策略协同作用，既增加了神经解剖的可塑性，又增加了功能 恢复。建议的研究将在成年大鼠的C3/C4(CHX)处使用颈髓过半切。这 损伤使我们能够比较直接和完全受损的通路的可塑性与血管重构 完好无损的道路。我们的研究表明，通路的再生既直接受损，又 备用通路的重组有助于功能的恢复。这种模式还允许我们 检查熟练的前肢功能和运动能力的恢复情况。建议的研究将检视 特异性药物干预对神经元内cAMP升高的影响及康复对策 增强神经解剖可塑性和功能恢复的活性。将应用干预措施 在受伤后立即(急性)、延迟2周后(亚急性)和延迟3个月后(慢性)。我们会 使用定量神经解剖学和行为学技术以及最先进的功能成像方法 对损伤后的解剖和功能进行纵向重组，并确定其作用。 观察特定重塑对功能恢复的影响。我们将检查解剖结构的范围 ？出现在具有代表性的棘上和脊椎区域的组织：感觉运动皮质和红色 核团(与熟练运动有关的棘上通路)，位于延髓神经元(一种通路) 与运动有关)，在背柱系统(上升感觉通路)，在脊髓 损伤的吻端和尾端的固有脊髓和运动神经元(与平衡相关的节段性通路 和协调)。我们还将确定运动功能恢复的时间进程和程度。 这里概述的实验将使我们更好地理解 以及如何对它们进行监管，并将在康复战略中发挥重要作用，以增加 脊髓损伤后神经可塑性与功能恢复。

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.