NERVE GROWTH FACTOR PROTECTS SENSORY NEURONS AFTER

神经生长因子在术后保护感觉神经元

• 批准号: 3083723
• 负责人: KEITH M RICH
• 金额: $ 6.96万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-02-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3083723
• 关键词: afferent nerve; denervation; dorsal root; motor neurons; nervous system regeneration; neuronal transport; neuropharmacology; neurosurgery; neurotrophic factors; peripheral nervous system; radiotracer

The ultimate goal of this project is to improve clinical recovery following neuronal injury with the intervention of pharmacological doses of a neurotropic factor at the time of the insult. The ability of pharmacological doses of nerve growth factor (NGF) to ameliorate the deleterious effects of injury upon the neuronal cell body will be evaluated. NGF will be applied locally at the site of injury via a silicone chamber. From preliminary experiments, NGF applied in this fashion has been shown to protect against the normally-occurring cell death and to prevent the neuronal atrophy which occurs after axotomy. The following experiments will characterize this protection in injured sensory neurons. These experiments will provide insight into the pharmacological potential of NGF to ameliorate the effects of axotomy on sensory neurons (e.g. protect against cell death) and perhaps improve functional recovery after injury. In a more general sense, it will provide a model of ways in which other neurotropic factors yet to be discovered (e.g. for motor neurons) could likewise be used as pharmacological agents to enhance functional recovery following injury. Specifically, the studies will examine the neuronal cell body reaction in rat lumbar dorsal root ganglia (DRG) neurons after ipsilateral axotomy of the sciatic nerve. The influence of the type of lesion and surgical manipulation upon the DRG neuron will be evaluated systematically by counting DRG neurons and by performing computer-assisted morphometric analysis of neuronal size. The capability of NGF, supplied via reservoirs at the injury site, to alter the neuron reaction to the injury will be examined with similar techniques. The protective role of NGF will be studied in experiments evaluating regeneration following sciatic nerve injury to determine whether NGF will provide permanent effects and improvement in functional recovery. Regeneration will be evaluated with both physiological (pinch test and axonal transport of radioisotype) and histological (axonal counts and morphometric analysis) techniques. Changes in the neuropeptide levels (substance P and extralysosomal acid phosphatases) in the dorsal horn of the spinal cord will be measured after injury to compare the ability of NGF to alter transganglionic degenerative atrophy of the DRG neurons. Experiments will determine whether these changes are permanently altered after treatment with NGF. The final experiments will study axonal growth through an NGF-containing silicone chamber by using histologic and axonal transport techniques as in above experiments.

该项目的最终目标是改善临床恢复 神经元损伤A的干预A 侮辱时的神经性因素。 能力 神经生长因子（NGF）的药理剂量以改善 受伤对神经元细胞体的有害影响将是 评估。 NGF将通过A本地应用于伤害部位 有机硅腔。 从初步实验中，NGF应用于此 时尚已被证明可以防止正常出现的细胞死亡 并防止轴突切开术后发生的神经元萎缩。 这 在实验之后将表征受伤的感觉的这种保护 神经元。 这些实验将为药理学提供洞察力 NGF改善轴切开术对感觉神经元的影响 （例如防止细胞死亡），也许可以改善功能恢复 受伤后。 从更一般的意义上讲，它将提供一种方式 尚未发现哪些其他神经性因素（例如电动机 神经元）同样可以用作药理剂来增强 受伤后的功能恢复。 具体而言，研究将检查神经元细胞体反应 大鼠腰背根神经节（DRG）神经元在同侧轴切开术后 坐骨神经。 病变和外科手术的影响 对DRG神经元的操作将通过 计算DRG神经元并执行计算机辅助形态计量学 神经元大小的分析。 NGF的能力，通过储层提供 在伤害部位，改变神经元对损伤的反应将是 使用类似的技术进行了检查。 NGF的保护作用将是 在评估坐骨神经后再生的实验中进行了研究 伤害以确定NGF是否会提供永久影响和 功能恢复的改善。 再生将通过 生理学（放射性型的捏测和轴突运输）和 组织学（轴突计数和形态分析）技术。 更改 在神经肽水平（物质P和牙入牙外酸）中 磷酸酶）在脊髓背角中将测量 损伤以比较NGF改变反式传播退化的能力 DRG神经元的萎缩。 实验将确定是否 用NGF处理后，变化会永久改变。 决赛 实验将通过含NGF的硅酮研究轴突生长 通过使用组织学和轴突运输技术，如上所述 实验。