Use of GDNF in the repair of spinal cord injury

GDNF在脊髓损伤修复中的应用

• 批准号: 6541987
• 负责人: CHRISTOPHER A IANNOTTI
• 金额: $ 2.56万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-31 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6541987
• 关键词: Schwann cells; axon; confocal scanning microscopy; disease /disorder model; electron microscopy; glia; growth factor receptors; immunocytochemistry; immunoelectron microscopy; laboratory rat; light microscopy; microsurgery; nervous system regeneration; neuronal transport; neurons; neurotrophic factors; pharmacokinetics; spinal cord injury; synapses; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): Each year in the U.S. there are an estimated 10,000 new spinal cord injury (SCI) cases, and there are an estimated 200,000 patients living with chronic SCI. SCI destroys neuronal connectivity by severing descending motor and ascending sensory pathways. Such damage results in permanent paralysis and loss of sensation below the level of injury. Cavitation or formation of a gap inevitably occurs due to secondary injury events. A bridging strategy using Schwann cell (SC)-seeded guidance channels can effectively promote regeneration of injured axons across the lesion gap. Additional treatments aiming at overcoming formidable barriers at the distal graft-host interface can further axonal growth. The goal of this investigation is to 1) improve axonal ingrowth into the bridge environment by adding glial cell line-derived trophic factor (GDNF) into SC-grafts, 2) promote significant axonal outgrowth and synaptic reconnection in the distal spinal cord and 3) define mechanisms by which GDNF promotes regeneration of injured axons. To accomplish this, a rat model of spinal cord hemisection and SC-seeded minichannel implantation will be used to establish that GDNF promotes substantial axonal regeneration across the SC-seeded bridge, re-entry into the distal host spinal cord, and reconnection with target neurons. The mechanisms underlying the action of GDNF will also be addressed. Experimental methods and techniques to be used include cell culture, animal microsurgery, immunohistochemistry, light and electron microscopy, confocal microscopy, anterograde and retrograde tracing, immunoelectron microscopy, and Western blotting.

描述(由申请者提供)：在美国，每年都有 估计有10,000例新的脊髓损伤(SCI)病例，估计有 20万慢性脊髓损伤患者。脊髓损伤通过以下方式破坏神经元连接 切断下行运动和上行感觉通路。这样的破坏结果是 在永久性瘫痪和受伤水平以下失去知觉。 由于继发性损伤，不可避免地会发生空化或形成缝隙。 事件。一种使用雪旺细胞(SC)种子引导通道的桥接策略 能有效促进损伤轴突跨越病变间隙的再生。 旨在克服远端严重障碍的附加治疗 移植物-宿主界面可促进轴突生长。这次调查的目的是 1)通过添加神经胶质细胞来改善桥环境中的轴突生长 细胞系衍生营养因子(GDNF)导入干细胞移植物，2)促进显著 脊髓远端轴突生长和突触重联 明确GDNF促进受损轴突再生的机制。至 为此，建立了大鼠脊髓半横断和SC-Seed模型 微通道植入将用于确定GDNF促进 大量轴突再生穿过SC-种子桥，重新进入 宿主脊髓远端，以及与目标神经元的重新连接。其作用机制 还将讨论GDNF行动的根本问题。实验方法和方法 将使用的技术包括细胞培养、动物显微外科手术、 免疫组织化学，光学和电子显微镜，共聚焦显微镜， 顺行和逆行示踪、免疫电子显微镜和Western 吸墨水。