CYTOKINES AND GROWTH FACTORS ROLE IN CNS SELF REPAIR

细胞因子和生长因子在中枢神经系统自我修复中的作用

• 批准号: 6243730
• 负责人: STEPHEN W SCHEFF
• 金额: $ 13.37万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243730
• 关键词: behavior test; brain injury; calcium flux; cytokine; disease /disorder model; electron microscopy; fibroblast growth factor; growth factor; histopathology; hypoglycemia; immunocytochemistry; insulinlike growth factor; interleukin 1; interleukin 6; laboratory rat; nervous system regeneration; neural growth associated protein; neural plasticity; neuroprotectants; neurotrophic factors; phase contrast microscopy; synaptogenesis; tissue /cell culture

Brain injury as a result of head trauma is a major health problem in the United States. Presently, little is known about the complex response of the CNS following cortical and injury and what possible therapeutic regimes can be employed to assist in recovery. When injured, growth- quiescent neurons in the CNS initiate a reactive repair process which appears to underlie functional recovery. This process can only be successful if the basic substrate, viable neurons and processes, are available. A common outcome of head trauma is secondary neuronal injury which appears to progress temporally and renders potentially reactive tissue unresponsive. Cytokines, secreted by injury-activated brain cells, initiate the production of numerous trophic factors that may protect neuron and their processes from secondary injury, thus promoting brain self-repair. Proposed experiments will explore the mechanisms involved in the injured cortex to compensate following focal trauma. These studies use a reliable animal model of brain injury in F344 rats caused by controlled cortical deformation. Study 1 examines the hypothesis that following cortical contusion, the injured brain activates a self-repair process and replaces lost synaptic connections. These experiments involve quantitative light and ultrastructural techniques. Study 2 examines the hypothesis that following injury there is a temporal sequence in the production of specific CNS protein which play a role in the compensatory process. These experiments involve quantitative immunocytochemistry and biochemical techniques to assess regional distribution after injury. Study 3 examines the hypothesis that cytokines and trophic agents influence neuronal plasticity and survival by affecting cellular calcium (Ca2+) homeostasis. These in vitro experiments will study the effects of IL-1 & 6 and NGF,bFGF,IGF-1 and IGF-II on neurite outgrowth and cell survival coupled with pharmacological manipulations of Ca2+. Possible modulatory effects of these agents on hypoglycemic and anoxic neuronal damage will be examined. Study 4 examines the hypothesis that intraventricular infusion of cytokines and trophic factors can enhance the self-repair process by altering cell survival and synapse replacement. Experiments involved the micro-infusion of trophic factors such as nerve growth factor (NGF), basic fibroblast growth factor (bFGF), insulin-like growth factor-I&II (IGF-1; IGF-II) and ultrastructural evaluation of the neuropil.

头部外伤导致的脑损伤是人类的一个主要健康问题 美国。 目前，人们对复杂的反应知之甚少。 皮质和损伤后的中枢神经系统以及可能的治疗方法 可以采用一些制度来帮助恢复。 当受伤时，成长—— 中枢神经系统中的静止神经元启动反应性修复过程 似乎是功能恢复的基础。 这个过程只能是 如果基本基质、可行的神经元和过程是成功的 可用的。 头部外伤的常见后果是继发性神经元损伤 这似乎暂时进展并呈现出潜在的反应性 组织无反应。 细胞因子，由损伤激活的大脑分泌 细胞，启动许多营养因子的产生，这些因子可能 保护神经元及其过程免受二次损伤，从而促进 大脑自我修复。 拟议的实验将探索其机制 参与受伤的皮质以补偿局灶性创伤。 这些研究使用 F344 大鼠脑损伤的可靠动物模型 由受控皮质变形引起。 研究 1 检验了以下假设：皮质挫伤后， 受伤的大脑激活自我修复过程并替代丢失的突触 连接。 这些实验涉及定量光和 超微结构技术。 研究 2 检验了以下假设：受伤后会出现暂时性的 特定中枢神经系统蛋白生产中的序列，该蛋白在 补偿过程。 这些实验涉及定量 免疫细胞化学和生化技术来评估区域 受伤后的分布。 研究 3 检验了以下假设：细胞因子和营养剂 通过影响细胞钙来影响神经元可塑性和存活 (Ca2+) 稳态。 这些体外实验将研究效果 IL-1 和 6 以及 NGF、bFGF、IGF-1 和 IGF-II 对神经突生长和细胞的影响 生存与 Ca2+ 的药理学操作相结合。 可能的 这些药物对低血糖和缺氧神经元的调节作用 将检查损坏情况。 研究 4 检验了以下假设：脑室内输注 细胞因子和营养因子可以通过以下方式增强自我修复过程 改变细胞存活和突触替换。 实验涉及 微量输注营养因子，例如神经生长因子（NGF）， 碱性成纤维细胞生长因子 (bFGF)、胰岛素样生长因子-I&II （IGF-1；IGF-II）和神经纤维的超微结构评估。