CNS REGENERATION IN NEONATAL AND ADULT SPINAL CORD

新生儿和成人脊髓的中枢神经系统再生

• 批准号: 3075100
• 负责人: BARBARA S BREGMAN
• 金额: $ 6.57万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3075100
• 关键词: axon; central nervous system; central nervous system disorders; glia; histochemistry /cytochemistry; immunochemistry; immunocytochemistry; injury; laboratory rat; nervous system regeneration; nervous system transplantation; neural information processing; neurogenesis; neurons; newborn animals; spinal cord; synapses; tissue /cell culture

The rules which determine the response of the immature CNS neurons to damage, the mechanisms which underlie the anatomical and functional reorganization that follows early CNS damage, and the factors which prevent more successful reorganization in the adult CNS are only poorly understood. We have demonstrated that neural tissue transplants modify the response of immature neurons to damage by 1) preventing the massive retrograde cell death of immature axotomized neurons and 2) supporting axonal elongation through the transplant and across the site of a neonatal lesion. The current proposal is designed to examine the mechanisms by which transplants modify the response of the immature CNS to damage. We will grow neural tissue transplants within spinal cord lesions in newborn rats to test the hypothesis that there are three requirements of damaged developing central neurons for survival. The first series of experiments will examine whether transplants provide a) a temporary trophic support for the immature axotomized neurons, b) a terrain which supports axonal elongation, and c) test whether the long-term survival after injury requires that the axotomized neurons establish or re-establish specific synaptic connections. We will determine the extent to which each of these requirements for survival is target specific. After lesions in the developing nervous system, in contrast to the adult, some axons are capable of long distance growth. The second series of experiments in this proposal will test whether this greater capacity for axonal elongation is regulated by factors intrinsic to the developing neurons or whether changes in the environment of the developing spinal cord limit the extent of axonal growth. We will first determine whether the long distance axonal growth in the immature nervous system is continued growth by late-developing axons or regenerative growth by damaged axons. We will test if there is a critical period in the developing spinal cord that permits long distance growth and examine whether immature glia play a role in creating this environmental. We will use transplantation, neuroanatomical tracing (immunocytochemistry, horseradish peroxidase, and fluorescent tracers) at light and electron microscopic levels and tissue culture techniques to address these questions.

决定未成熟中枢神经系统神经元反应的规则 损害，解剖学和 早期中枢神经系统损伤后的功能重组，以及 阻碍成人更成功重组的因素 对中枢神经系统的了解还很有限。 我们已经证明神经 组织移植改变未成熟神经元的反应 1）防止大规模逆行性细胞死亡 未成熟的轴突神经元和 2) 支持轴突伸长 穿过移植物并穿过新生儿病变部位。 当前的提案旨在审查以下机制： 移植改变了未成熟的中枢神经系统对损伤的反应。 我们 将在脊髓病变内生长神经组织移植物 新生大鼠测试以下假设：存在三种 受损发育中的中枢神经元生存的需求。 第一系列实验将检查移植是否 为未成熟的轴突提供暂时的营养支持 神经元，b) 支持轴突伸长的地形，以及 c) 测试 受伤后的长期生存是否需要 轴突神经元建立或重建特定的突触 连接。 我们将确定其中每一项的程度 生存的要求是特定于目标的。 病变发生后 发育中的神经系统，与成人相比，一些轴突 能够长距离生长。 第二系列实验 在这个提案中将测试这种更大的轴突能力是否 伸长率受发育中固有因素的调节 神经元或发育中的环境是否发生变化 脊髓限制轴突生长的程度。 我们首先会 判断长距离轴突生长是否处于未成熟状态 神经系统通过发育迟缓的轴突持续生长或 受损轴突的再生生长。 我们将测试是否有 脊髓发育的关键时期，允许长时间 距离生长并检查未成熟的神经胶质细胞是否在 创造这个环境。 我们将使用移植， 神经解剖学追踪（免疫细胞化学、辣根 过氧化物酶和荧光示踪剂）在光和电子下 微观水平和组织培养技术来解决这些问题 问题。