The Functionality of the Regenerated Corticospinal Tract

再生皮质脊髓束的功能

• 批准号: 6998595
• 负责人: KAHLIL J MARTIN
• 金额: $ 1.29万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-07 至 2006-01-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6998595
• 关键词: Adenoviridae; behavior test; biotechnology; confocal scanning microscopy; disease /disorder model; electron microscopy; electrophysiology; electrostimulus; evoked potentials; gene expression; gene therapy; laboratory rat; motor neurons; nervous system disorder therapy; nervous system regeneration; neural plasticity; neuromuscular function; neuronal guidance; neurotrophic factors; nonhuman therapy evaluation; predoctoral investigator; pyramidal tracts; sciatic nerve; spinal cord injury; synaptogenesis; transfection /expression vector

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.

描述（由申请人提供）：本项目的目的是评估使用腺病毒转导运动神经元（一种治疗脊髓损伤的基因治疗方法）过度表达神经营养因子（NT-3、BDNF和GDNF）导致的出芽轴突的功能。功能评估将使用容纳皮质脊髓神经元的运动区域的皮质刺激的比较电生理学技术来完成，然后从后肢的外周神经（坐骨神经）进行运动诱发电位（MEP）的细胞外记录。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，以评价分子标记物BDA和突触素的共定位，其指示CST内的功能性突触。为了测试与轴突发芽相关的功能的潜在获得的行为后果，将进行CST在大鼠中负责的肢体瞄准和肢体放置的测试。这项研究的最终目的是评估腺病毒过度表达神经营养因子后运动系统功能的任何增益。