CNS REGENERATION IN NEONATALS AND ADULTS

新生儿和成人的中枢神经系统再生

• 批准号: 3399272
• 负责人: BARBARA S BREGMAN
• 金额: $ 21.48万
• 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 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3399272
• 关键词: axon; biological models; brain stem; central nervous system; electron microscopy; extracellular matrix; fluorescence; immunocytochemistry; laboratory rat; nervous system regeneration; nervous system transplantation; neuroanatomy; neurogenesis; neuronal guidance; newborn animals; protein biosynthesis; pyramidal tracts; spinal cord injury; spinal cord surgery; synapses

The purpose of the proposed research is to elucidate the rules which determine the response of immature CNS neurons to damage, the mechanisms which underlie the anatomical and functional reorganization that follows early CNS damage, and the factors which permit more successful reorganization i the neonate than in the adult CNS. We have demonstrated previously that embryonic neural tissue transplants modify the response of the immature spinal cord to damage by rescuing immature axotomized neurons from retrograde cell death and by supporting the growth of axons from the host CNS into the transplant. Spinal cord to spinal cord (homonymous) transplants support the persistent survival of axotomized neurons and elongation of their axons, whereas heteronymous (non-spinal cord) transplants only temporarily support this reorganization. Thus permanent reorganization resulting in recovery and/or sparing of function is a target-specific effect of the transplant. The current proposal is designed to identify cellular and molecular mechanisms underlying neuronal survival and axonal elongation after injury in the developing nervous system. We will determine the degree to which the capacity of immature CNS neurons for survival and axonal elongation after injury is regulated by factors intrinsic to the developing neuronal systems (for example the presence of axonal collaterals, ongoing synthesis of growth associated proteins) and the degree to which extrinsic environmental conditions (such as the presence of particular extracellular matrix components) regulate survival and growth and the degree to which intrinsic and extrinsic factors interact. Our model system (spinal cord injury at birth) allows us to study the effect of transplants on the development of undamaged axons in the corticospinal tract and on the survival of axotomized brainstem-spinal tract cells and subsequent re-growth of their axons. We will use quantitative methods to compare developing and regenerating neuronal populations to determine the extent to which their requirements for survival and axonal elongation differ and the extent to which they are similar. We will use neural tissue transplantation n vivo, neuroanatomical tracing (immunocytochemistry, horseradish peroxidase, and florescent tracers) at light and electron microscopic levels and in vitro tissue culture techniques to address these questions.

拟议研究的目的是阐明规则 确定未成熟 CNS 神经元对损伤的反应、机制 这是随后的解剖学和功能重组的基础 早期中枢神经系统损伤，以及允许更成功的因素 新生儿中枢神经系统的重组程度高于成人中枢神经系统。 我们已经证明了 以前认为胚胎神经组织移植会改变反应 通过拯救未成熟的轴突来使未成熟的脊髓受损 逆行细胞死亡和支持轴突生长的神经元 从宿主中枢神经系统进入移植物。 脊髓到脊髓 （同名）移植支持轴突切除的持续存活 神经元及其轴突的伸长，而异名（非脊髓） 脐带）移植只能暂时支持这种重组。 因此 永久重组导致恢复和/或保留 功能是移植物的靶标特异性效应。目前的 该提案旨在识别细胞和分子机制 损伤后潜在的神经元存活和轴突伸长 神经系统发育。我们将确定该程度 未成熟中枢神经系统神经元存活和轴突伸长的能力 损伤是由发育中的神经元固有的因素调节的 系统（例如轴突侧支的存在、正在进行的 生长相关蛋白的合成）和程度 外部环境条件（例如特定环境的存在） 细胞外基质成分）调节存活和生长， 内在因素和外在因素相互作用的程度。 我们的模型 系统（出生时脊髓损伤）使我们能够研究 移植对皮质脊髓未受损轴突发育的影响 束和轴突型脑干脊髓束细胞的存活 随后轴突重新生长。 我们将使用定量方法 比较发育中和再生的神经元群体以确定 他们对生存和轴突伸长的要求的程度 差异以及相似程度。 我们将使用神经网络 体内组织移植、神经解剖追踪 （免疫细胞化学、辣根过氧化物酶和荧光示踪剂） 光和电子显微镜水平以及体外组织培养 技术来解决这些问题。