CYTOKINES AND GROWTH FACTORS ROLE IN CNS SELF REPAIR

由于头部创伤导致的脑损伤是美国的主要健康问题， 美国的 目前，人们对这种复杂的反应知之甚少。 中枢神经系统皮层损伤后， 可以采用各种制度来帮助恢复。 当受伤时，生长- CNS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 成功的，如果基本基板，可行的神经元和过程， available. 头部外伤的常见后果是继发性神经元损伤 这似乎是暂时的进展， 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， 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 拟议的实验将探索机制 参与受损皮质以补偿局灶性创伤。 这些研究使用了F344大鼠脑损伤的可靠动物模型 是由皮质变形引起的 研究1检验了皮质挫伤后， 受伤的大脑激活自我修复过程， 连接. 这些实验涉及定量光， 超微结构技术 研究2检验了以下假设： 在特定CNS蛋白的产生中起作用的序列， 补偿过程。 这些实验涉及定量 免疫细胞化学和生物化学技术，以评估区域 受伤后的分布 研究3检验了细胞因子和营养因子 通过影响细胞钙离子影响神经元可塑性和存活 (Ca2+）体内平衡。 这些体外实验将研究 IL-1、6和NGF、bFGF、IGF-1和IGF-Ⅱ对神经突起生长和细胞增殖的影响 存活率与Ca 2+的药理学操作相结合。 可能 这些药物对低血糖和缺氧神经元的调节作用 损害将被检查。 研究4检验了脑室内输注 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和II （IGF-1; IGF-II）和超微结构评价的神经。

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.