AXONAL GROWTH IN THE CHRONICALLY INJURED SPINAL CORD

慢性损伤脊髓的轴突生长

• 批准号: 2265915
• 负责人: John D. Houle
• 金额: $ 17.47万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265915
• 关键词: axon; cell cell interaction; chronic disease /disorder; electrophysiology; embryo /fetus cell /tissue; fluorescent dye /probe; gene expression; gene induction /repression; laboratory rat; macrophage; monokines; nervous system regeneration; nervous system transplantation; neuronal guidance; neuronal transport; neurotrophic factors; peripheral nervous system; spinal cord; spinal cord injury; synapses

The long-term objectives of this study are to define the regenerative capabilities of chronically injured neurons associated with a spinal cord injury and to determine whether neurotransplantation approaches can lead to structural and functional repair of the traumatized spinal cord. The specific aims of this application are focused on identification of intrinsic neuronal properties that may influence either the capacity for regeneration or the ability to respond to exogenous neurotrophic factors (NTFs) with an enhanced regenerative effort. Additional experiments are designed to evaluate the role of specific non-neuronal cells (i.e. macrophages) in the initiation and early guidance of axonal regeneration and to examine the functional activity associated with the structural integration of regrowing axons with the host spinal cord. Aim 1 of this proposal will utilize a combination of NTF treatment with a peripheral nerve (PN) graft apposed to the injured cervical spinal cord to test whether the regenerative response of chronically injured supraspinal neurons can be enhanced. The second aim will use a similar injury/ transplantation model to evaluate immediate early gene expression in a chronic injury condition, during the regenerative response exhibited by some supraspinal neurons and after NTF treatment to enhance regeneration by other neurons. Immunocytochemical detection of Jun protein within neurons retrogradely labeled via a PN graft will determine whether up- regulation of cjun is a necessary step in the regenerative response. In the third Aim, experiments to promote the association of macrophages with an intraspinal nitrocellulose implant co-grafted with fetal spinal cord (FSC) tissue will determine the role of these non-neuronal cells in fostering regeneration from neurons involved in a spinal cord injury. Electrophysiological techniques will be applied in Aim IV to identify functional integration of regenerated axons with neurons of the host spinal cord. Efforts to detect synaptic activity will utilize FSC tissue transplants or PN grafts as conduits for guidance of axonal growth across a spinal cord lesion. These experiments will provide valuable information about molecular, cellular and functional aspects of axonal regeneration associated with a long term spinal cord injury and will help in the design of possible combinations of surgical, trophic factor or genetic intervention to promote spinal cord repair.

这项研究的长期目标是定义再生 与脊髓相关的长期损伤神经元的功能 伤害并确定神经移植方法是否可以领导 进行创伤性脊髓的结构和功能修复。这 本应用的具体目的是识别 固有的神经元特性可能会影响 再生或对外源性神经营养因素反应的能力 （NTF）以增强的再生努力。其他实验是 旨在评估特定非神经元细胞的作用（即 巨噬细胞）在轴突再生的启动和早期指导中 并检查与结构相关的功能活性 将轴突与宿主脊髓整合。目标1 提案将利用NTF治疗与外围的组合 神经（pn）移植物上置于受伤的宫颈脊髓上进行测试 长期受伤的脊柱上的再生反应是否 神经元可以增强。第二个目标将使用类似的伤害/ 移植模型以评估A中立即的早期基因表达 慢性损伤状况，在再生反应期间 一些脊柱上神经元和NTF治疗后以增强再生 由其他神经元。 JUN蛋白内的免疫细胞化学检测 通过PN移植物逆行标记的神经元将确定是否上升 CJUN的调节是再生反应的必要步骤。在 第三个目的是促进巨噬细胞与 与胎儿脊髓共植物的载体内硝酸纤维素植入物 （FSC）组织将确定这些非神经细胞在 促进涉及脊髓损伤的神经元的再生。 电生理技术将应用于目标IV以识别 再生轴突与宿主神经元的功能整合 脊髓。检测突触活动的努力将利用FSC组织 移植或PN移植物作为指导轴突生长的导管 脊髓病变。这些实验将提供有价值的信息 关于轴突再生的分子，细胞和功能方面 与长期脊髓损伤相关，将有助于设计 手术，营养因子或遗传的可能组合 干预以促进脊髓修复。