NEUROTROPHIC FACTORS IN SPINAL CORD TRAUMA

脊髓创伤中的神经营养因素

• 批准号: 2271015
• 负责人: Italo Mocchetti
• 金额: $ 21.39万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2271015
• 关键词: RNA biosynthesis; blocking antibody; cell type; corticosteroids; fibroblast growth factor; gene induction /repression; glia; glutamate receptor; immunocytochemistry; in situ hybridization; laboratory rat; neuropharmacology; neurophysiology; neurotrophic factors; nonsurgical revascularization; protein biosynthesis; reflex; sensorimotor system; spinal cord injury; trauma; western blottings

Neurotrophic factors appear to be crucial for the survival and potential regeneration of injured neurons. Injury of the peripheral nervous system results in the induction of a number of neurotrophic molecules. Less is known about the response of central nervous tissue to injury. We have examined levels of mRNA for three trophic factors, basic and acidic fibroblast growth factor (bFGF, aFGF), and nerve growth factor (NGF), after an incomplete thoracic contusive spinal cord injury (SCI). RNase protection assays showed a rapid increase (three-fold) in the content of bF6F mRNA by 6 hours that persisted for at least 7 days after SCI. The induction of bFGF was specific, as no change in the levels of aFGF or NGF mRNA were seen. These data support a speculative hypothesis that bFGF may play a role in the partial recovery of function seen following incomplete contusive spinal cord injury. We propose to test this hypothesis. We will determine whether bFGF protein levels are also increased after SCI by immunohistochemistry, Western blot analysis and proliferation assays. Moreover, we will determine the location and cell types in which bFGF mRNA and protein are induced with respect to the injury epicenter, by in situ hybridization and immunohistochemistry. We will test specific hypotheses that the induction of bFGF after SCI is important for a) neovascularization, as well as b) neuronal survival and c) the glial reaction, following SCI. We will investigate the potential pharmacological manipulation of bFGF induction with corticosteroids, and glutamate receptor antagonists, classes of drugs that have been shown capable of enhancing functional recovery after traumatic SCI. These studies offer promise in understanding the mechanisms leading to the induction of bFGF in the CNS, as well as a potential new therapeutic approach to SCI. On the basis of experimental and/or pharmacological manipulation of bFGF levels, we will then rigorously test the hypothesis that bFGF plays a significant role in the observed partial recovery of sensori-motor function after SCI. Lastly, we will begin to place the induction of bFGF in the context of the overall neurotrophic environment in the spinal cord after injury. by initiating studies on the induction of Brain. Derived Neurotrophic Factor (BDNF) after SCI. We expect that the results from this project should provide important insights into natural, endogenous, recovery mechanisms in the CNS that can in the future be therapeutically manipulated.

神经营养因素似乎对生存和潜力至关重要 受伤神经元的再生。周围神经系统的伤害 导致许多神经营养分子的诱导。 少是 知道中枢神经组织对损伤的反应。 我们有 检查了三种营养因子的mRNA水平，碱性和酸性 成纤维细胞生长因子（BFGF，AFGF）和神经生长因子（NGF）， 在胸腔不完整的脊髓损伤（SCI）之后。 RNase 保护测定显示的含量迅速增加（三倍） BF6F mRNA在SCI后至少7天持续了6个小时。这 BFGF的诱导是具体的，因为AFGF或NGF的水平没有变化 看到mRNA。 这些数据支持BFGF可能的推测假设 在不完整后看到的功能的部分恢复中发挥作用 脊髓损伤。 我们建议检验这一假设。 我们 将确定SCI后BFGF蛋白水平是否也提高了 免疫组织化学，蛋白质印迹分析和增殖分析。 此外，我们将确定BFGF mRNA的位置和细胞类型 和蛋白质相对于损伤震中诱导 杂交和免疫组织化学。我们将检验特定的假设 SCI后BFGF的诱导对于A） 新血管形成，以及b）神经元存活和c）神经胶质 反应，后期科学。 我们将调查潜力 用皮质类固醇对BFGF诱导的药理操作，以及 谷氨酸受体拮抗剂，已显示的一类药物 创伤后能够增强功能恢复。这些 研究提供了理解导致的机制的希望 CNS中BFGF的诱导以及潜在的新治疗 科学的方法。 根据实验和/或药理 操纵BFGF水平，然后我们将严格检验假设 BFGF在观察到的部分恢复中起着重要作用 科学后的感觉运动函数。 最后，我们将开始放置 在整体神经营养环境的背景下诱导BFGF 受伤后的脊髓。通过启动有关诱导的研究 脑。科学后衍生的神经营养因子（BDNF）。我们期望 该项目的结果应提供对自然的重要见解 中枢神经系统的内生，恢复机制将来可能是 治疗上操纵。