RESPONSE OF CULTURED MOLLUSK NEURONS TO INJURY

培养的软体动物神经元对损伤的反应

• 批准号: 3429181
• 负责人: DENNIS G EMERY
• 金额: $ 6.2万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3429181
• 关键词: Gastropoda; axon; axon reaction; body temperature; calcium flux; cell death; cell membrane; cytoskeleton; electron microscopy; extracellular matrix; fluorimetry; histopathology; mitochondria; nervous system regeneration; neurons; tissue /cell culture; trauma; vesicle /vacuole

The goal of this research is to better understand the cellular mechanisms by which neurons respond to physical trauma, including the recovery from sub-lethal injury and the processes leading to death after a lethal insult. A new model for such research will be developed and defined, and it will be used to investigate the efficacy of treatments that may improve the prospects of neuronal survival after injury. Molluscan neurons have great ability to recover from injury. One specific alm of the proposed research is to define the responses of cultured neurons from the snail, Helisoma trivolvis, to mechanical injury and to compare these responses to those of mammalian neurons. The model will be defined by determining the effect of axotomy on neuronal survival. The parameters of a lesion (distance from the perikaryon and lesion diameter) that will produce a predictable neuronal survival rate will be determined, and this standardized axotomy paradigm will be used to test factors that may alter neuronal recovery after injury. Since molluscs have lower body temperatures than mammals, the importance of temperature in the recovery of neurons after injury will be determined. Pathological changes in the ultrastructure of the cultured neurons after injury will also be observed and compared to those that have been reported in similarly injured mammalian neurons. Changes in ultrastructure of injured neurons will be correlated with measured levels of intracellular free calcium by using calcium sensitive fluorescent dye fluorimetry. The process by which the severed axon reseals after axotomy will be investigated by measuring the dynamics of changes in membrane electrical properties after axotomy. Agents which may alter this resealing process will be tested on the culture model,and their effects on resealing and neuronal viability will be determined.

这项研究的目的是更好地了解细胞机制 神经元应对身体创伤的反应，包括从 致命损伤后导致死亡的过程以及导致死亡的过程。 将开发和定义此类研究的新模型，这将是 用于研究可能改善的治疗的功效 受伤后神经元存活的前景。 软体动物神经元具有很高的损伤能力。一个具体 拟议的研究的ALM是定义培养神经元的反应 从蜗牛，旋律trivolvis到机械损伤，并比较 这些对哺乳动物神经元的反应。该模型将由 确定轴切开术对神经元存活的影响。一个参数 病变（距离周围和病变直径的距离）将产生 将确定可预测的神经元存活率，这 标准化的轴切开术将用于测试可能改变的因素 受伤后神经元恢复。 由于软体动物的体温低于哺乳动物，因此 损伤后神经元恢复中的温度将确定。 培养神经元超微结构之后的病理变化 也将观察到伤害，并将其与已报告的伤害进行比较 在类似受伤的哺乳动物神经元中。超微结构的变化 受伤的神经元将与测量的细胞内水平相关 通过使用钙敏感荧光染料荧光法的游离钙。 轴突切开后切断的轴突重新密封的过程将是 通过测量膜电的变化的动力学研究 轴切开后的性质。可能会改变此重新关闭过程的代理商 将在文化模型上进行测试，并将其对重新密封的影响和 将确定神经元的生存能力。