The Functionality of the Regenerated Corticospinal Tract

描述(申请人提供)：本项目的目标是评估神经营养因子(NT-3、BDNF和GDNF)过度表达所导致的发芽轴突的功能，使用腺病毒转导运动神经元，这是一种治疗脊髓损伤的基因治疗方法。功能评估将使用对含有皮质脊髓神经元的运动区进行皮质刺激的比较电生理学技术来完成，然后对后肢周围神经(坐骨神经)的运动诱发电位(MEP)进行细胞外记录。为了开始测试突触功能，将使用共聚焦显微镜进行成像研究，以评估指示CST内功能性突触的分子标志物BDA和突触素的共存情况。为了测试与轴突萌发相关的潜在功能获得的行为后果，将在大鼠身上进行肢体瞄准和肢体放置的测试，CST负责这些测试。这项研究的最终目标是评估腺病毒传递的神经营养因子过表达后运动系统功能的任何获得。

DESCRIPTION (provided by applicant): The goal of this project is to assess the function of sprouting axons resulting from the overexpression of neurotrophic factors (NT-3, BDNF, and GDNF) using adenoviral transduction of motoneurons, a gene therapy approach to the treatment of spinal cord injury. The functionality assessment is to be accomplished using comparative electrophysiology techniques of cortical stimulation of motor areas housing corticospinal neurons and then make extracellular recordings of motor evoked potentials (MEPs) from a peripheral nerve of the hind limb, the sciatic nerve. To begin to test synaptic function imaging studies will be done using confocal microscopy to evaluate the colocalization of molecular markers, BDA and synaptophysin, indicative of functional synapses within the CST. To test the behavioral consequences of a potential gain of function associated with the axon sprouting, tests of limb aiming and limb placement, for which the CST is responsible in rat, will be conducted. The ultimate goal of the investigation is to assess any gain of function in the motor system following the overexpression of neurotrophic factors delivered by adenovirus.