CYTOKINES AND GROWTH FACTORS ROLE IN CNS SELF REPAIR

头部创伤导致的脑损伤是中国的一个主要健康问题。 美国。目前，人们对病毒的复杂反应知之甚少。 皮质和损伤后的中枢神经系统及其可能的治疗 可以利用各种制度来协助恢复。当受伤时，生长- 中枢神经系统中静止的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 如果基本底物、有活力的神经元和突起是 可用。头部创伤的常见结局是继发性神经元损伤。 它似乎在时间上进展，并呈现潜在的反应性 组织无反应。损伤激活脑分泌的细胞因子 细胞，启动大量营养因子的产生，这些营养因子可能 保护神经元及其突起免受继发性损伤，从而促进 大脑自我修复。拟议中的实验将探索这种机制 参与损伤的皮质，以补偿局灶性创伤后的损伤。 这些研究使用了一种可靠的F344大鼠脑损伤动物模型 由受控的皮质变形引起。 研究1检验了这样一种假设，即皮质挫伤后， 受伤的大脑启动自我修复过程，取代丢失的突触 关系。这些实验涉及到定量光和 超微结构技术。 研究2检验了这样一种假设，即在受伤之后会有一个颞叶 在特定的中枢神经系统蛋白的产生中起作用的序列 补偿过程。这些实验涉及定量的 免疫细胞化学和生化技术评估区域性 损伤后的分布。 研究3检验了细胞因子和营养因子的假设 影响细胞内钙离子对神经元可塑性和存活率的影响 (Ca2+)动态平衡。这些体外实验将研究这些影响 IL-1、6和NGF、bFGF、IGF-1、IGF-II对轴突生长和细胞生长的影响 存活与钙离子的药理操作相结合。可能的 这些药物对低血糖和缺氧性神经元的调节作用 将检查损坏情况。 研究4检验了脑室内输注药物的假设 细胞因子和营养因子可通过以下途径促进自我修复过程 改变细胞存活和突触替换。实验涉及的是 微量输注营养因子，如神经生长因子(NGF)， 碱性成纤维细胞生长因子、胰岛素样生长因子-I和II (IGF-1；IGF-II)和神经纤维束的超微结构评价。

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.