CNS REGENERATION IN NEONATES AND ADULTS

新生儿和成人的中枢神经系统再生

• 批准号: 2263560
• 负责人: BARBARA S BREGMAN
• 金额: $ 26.45万
• 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 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2263560
• 关键词: age difference; brain stem; central nervous system; developmental neurobiology; immunocytochemistry; in situ hybridization; laboratory rat; nervous system regeneration; nervous system transplantation; neuroanatomy; neuronal guidance; neuronal transport; neuroprotectants; neurotrophic factors; newborn animals; spinal cord injury; age difference; brain stem; central nervous system; developmental neurobiology; immunocytochemistry; in situ hybridization; laboratory rat; nervous system regeneration; nervous system transplantation; neuroanatomy; neuronal guidance; neuronal transport; neuroprotectants; neurotrophic factors; newborn animals; spinal cord injury

DESCRIPTION (Investigator's Abstract): The long range goal of this research program is to identify the requirements of developing and mature CNS neurons for survival and axonal regeneration after injury and to identify ways to enhance axonal sprouting and regenerative growth after spinal cord injury at birth or at maturity. Studies during the previous period of support using neural tissue transplantation techniques after spinal cord injury indicate that I) CN5 neurons (like their peripheral counterparts) are dependent upon target derived trophic support for neuronal survival and axonal elongation after injury, 2) particular populations of neurons have very specific requirements for survival and for tonal elongation after injury and 3) survival and axonal elongation are regulated independently. At present, little is known about the effects of exogenous trophic support on neuronal survival and axonal elongation in vivo. We are in a situation to test in vivo for CNS neurons for the first time many of the principles of neurotrophic influences CNS pathways during development and after injury which to date have been inaccessible to experimental manipulation. We will test the influence of members of the neurotrophin family (BDNF,NT-3, NT-4, NLF) and the injury related neurotrophic factor (CNTF) on CNS pathways during development, at maturity and after spinal cord injury. The studies proposed will examine systematically 3 representative classes of neurons: descending corticospinal neurons, descending brainstem spinal neuron and ascending neurons to determine the extent to which their requirements for survival and regrowth after injury are similar and the extent to which they differ. It is likely that CNS neurons require trophic support from their target not only during development but also in the adult, or that a lesion makes them dependent again in an immature fashion. We will use spinal cord lesions and transplants in newborn and adult rats and the administration of exogenous neurotrophic support to determine the requirements of CNS neurons for survival and growth after spinal cord injury and to identify ways to enhance that growth. We will use neural tissue transplantation, neuroanatomical tracing (anterograde and retrograde transport of horseradish peroxidase and fluorescent tracers, retrograde transport of neurotrophic factors, in situ hybridization, immunocytochemistry), quantitative morphometrics, and tissue culture techniques to address the specific aims. The experiments proposed will test the hypothesis that the admintration of exogenous trophic agents Bill increase the survival of innnature axotomized CNS neurons, prevent the atrophy of mature axotomized CNS neurons and increase the capacity of both mature and in immature neurons for regenerative growth after spinal cord injury and transplantation in neonatal and adult operates. We predict that particular strategies will enhance the survival, plasticity and regenerative growth of particular pathways after spinal cord injury during development and at maturity.

描述（调查员的摘要）：此的远程目标 研究计划是确定开发和 受伤后的成熟CNS神经元用于生存和轴突再生 确定增强轴突发芽和再生增长的方法 出生时或成熟时脊髓损伤后。在 使用神经组织移植的前期支持 脊髓损伤后的技术表明i）CN5神经元（例如 它们的外围对应物）取决于目标衍生的营养 损伤后的神经元存活和轴突伸长的支持，2） 特定的神经元种群对 生存和受伤后的音调伸长和3）生存和 轴突伸长受到独立调节。目前，几乎没有 已经知道外源营养支持对神经元存活的影响 和体内轴突伸长。我们正在体内测试 CNS神经元首次是神经营养的许多原理 影响开发期间和受伤后的CNS途径 日期无法访问实验操作。我们将测试 神经营养蛋白家族成员的影响（BDNF，NT-3，NT-4， NLF）和CNS途径上的损伤相关神经营养因子（CNTF） 在发育期间，成熟和脊髓损伤后。这 提出的研究将系统地检查3个代表性类别 神经元：降层皮质脊髓神经元，脑干下降 脊柱神经元和上升神经元，以确定 他们对受伤后生存和再生的要求相似 以及它们不同的程度。 CNS神经元可能 不仅需要在开发过程中，而且还需要其目标的营养支持 同样在成年人中，或者病变使它们再次依赖 不成熟的时尚。我们将在 新生儿和成年大鼠以及外源性神经营养的给药 支持确定中枢神经系统神经元生存和 脊髓损伤后的生长，并确定增强这种方法的方法 生长。 我们将使用神经组织移植，神经解剖学 追踪（辣根过氧化物酶的顺行和逆行运输 和荧光示踪剂，神经营养因子的逆行运输， 原位杂交，免疫细胞化学），定量形态计量学， 和组织培养技术以解决具体目的。这 提出的实验将检验以下假设 外源营养特工账单增加了内在的生存率 轴向CNS神经元，防止成熟的轴向CNS的萎缩 神经元并增加成熟和未成熟神经元的能力 脊髓损伤和移植后的再生生长 新生儿和成人运作。我们预测特定策略将 增强特定的生存，可塑性和再生生长 发育和成熟期间脊髓损伤后的途径。