Brain reorganization after spinal cord injury

描述（由申请人提供）：运动引起脑或周围神经损伤动物体感觉或运动皮质体位图的变化，这些变化与功能恢复有关。在脊髓损伤（SCI）的情况下，运动也可以促进恢复，但运动对脊髓损伤后皮质组织的影响尚不清楚。脊髓损伤对皮质组织的影响已经得到了很好的研究，脊髓损伤可以通过两种方式改变体位图。第一种有时被称为“沉默”。这是指受损伤影响最大的体感觉皮层区域对任何皮肤刺激都没有反应的情况。第二种可能是，受影响的区域形成了一种新的体位组织，使得该区域的细胞对从脊柱节段吻侧到损伤处神经支配的外周区域的刺激作出反应。脊髓损伤后的皮质可塑性可能有助于学习新的感觉运动策略，以最大限度地恢复。然而，运动对脊髓损伤后皮质组织的影响很少得到解决。因此，脊髓损伤后皮质组织变化与功能恢复之间的关系尚不清楚。本研究的目的是确定脊髓损伤后治疗干预引起的皮层重组是否有助于改善功能恢复。为了确定这一点，我们将确定皮层重组和功能恢复之间的关系。我们的中心假设是，中胸横断后皮层神经元回路的重组是功能恢复所必需的。我们的初步数据表明，接受治疗干预以改善功能恢复的中胸椎横断大鼠显示出大脑皮层的新组织，使脊髓化后皮层的去神经区不再沉默。此外，在新生儿脊柱化的大鼠中，实现体重支撑行走，新的皮质组织与功能恢复相关。因此，我们认为，皮层的重组可能在功能恢复中发挥重要作用。我们的中心假设将通过两个特定目的来验证：目的1评估感觉运动皮层重组在接受运动作为治疗干预的脊髓化大鼠功能恢复中的作用。目的2：探讨运动联合5 -羟色胺药物治疗后感觉运动皮层重组在脊髓大鼠功能恢复中的作用。

DESCRIPTION (provided by applicant): Exercise induces changes in somatotopic maps of the somatosensory or motor cortices of animals with brain or peripheral nerve injuries and these changes are related to functional recovery. In the case of spinal cord injury (SCI), exercise also improves recovery, but the effect of exercise on cortical organization after SCI is not well understood. The effect of SCI alone on cortical organization is well studied and SCI can alter somatotopic maps in two ways. The first is sometimes referred to as "silencing". This refers to the case when the region of the somatosensory cortex most affected by the injury does not respond to any cutaneous stimulation. The second possibility is that the affected region develops a novel somatotopic organization, such that the cells in this region respond to stimulation of peripheral areas innervated from spinal segments rostral to the injury. Cortical plasticity after spinal cord injury is likely to aid in learning novel sensorimotor strategies to maximize recovery. However, the effect of exercise on cortical organization after spinal cord injury is rarely addressed. Therefore, the relationship between changes in cortical organization and functional recovery after SCI remains unclear. The goal of this proposal is to determine if the cortical reorganization induced in response to therapeutic interventions after SCI contributes to improved functional recovery. To determine this, we will identify the relationship between cortical reorganization and functional recovery. Our central hypothesis is that reorganization of neuronal circuits in the cortex after mid-thoracic transection is necessary for functional recovery. Our preliminary data suggest that rats with mid-thoracic transection that receive therapeutic interventions to improve functional recovery demonstrate novel cortical organization in the brain such that deafferentated regions of the cortex are no longer silent after the spinalization. Moreover, in neonatally spinalized rats that achieve weight supported stepping, the novel cortical organization is correlated with functional recovery. We suggest, therefore, that reorganization of the cortex may play an important role in functional recovery. Our central hypothesis will be tested using two Specific Aims: Aim 1 Evaluate the role of reorganization in the sensorimotor cortex on the functional recovery of spinalized rats that receive exercise as a therapeutic intervention. Aim 2 Evaluate the role of reorganization in the sensorimotor cortex on the functional recovery of spinalized rats that receive exercise combined with serotonergic pharmacotherapy. PUBLIC HEALTH RELEVANCE: Brain reorganization after spinal cord injury Spinal cord injury affects more than 200,000 individuals in the United States and approximately 10,000 more patients sustain spinal cord injuries each year. When a person receives an SCI, the communication between the brain and other parts of the body is disrupted, and messages no longer flow past the damaged area. The goal of this project is to understand plasticity in the brain so that after injury, the brain can reorganize to improve function in patients.