STROKE THERAPY MECHANISMS WITH NEUROTROPHIC FACTORS

几种药物已被证明可以减少各种神经损伤 通过治疗的关键药理作用， 在大多数情况下都没有详细说明。 寻找治疗方法， 预防或减少缺血性中枢神经系统损伤已经成为 由于对生物多样性的机制缺乏充分的基本了解， 损害 这在一定程度上是由模型不好造成的 旨在将生物化学、药理学和神经学 功能研究 最近在鉴定营养型的方面有了很大的进展， 因素 这些蛋白质有很多作用， 修复身体各部位的损伤。 他们也是 存在于中枢神经系统中。 有些似乎是必要的， 神经元群体的存活，有理由怀疑它们是 参与中枢神经系统损伤的反应。 几 这些因子刺激蛋白激酶，蛋白激酶是酶家族， 在这一系列事件中充当第二信使。 蛋白 激酶已经成为许多重要研究的焦点， 过去几年，因为他们的行为似乎负责的主要 许多细胞类型的活动，特别是在神经系统中。 我们假设蛋白质磷酸化的紊乱是一个主要的 不可逆缺血性神经损伤的发病原因。 此外，我们认为，营养因子可以调节中枢神经系统， 系统损害，至少部分是由于它们对蛋白质的作用 磷酸化 在这些研究中，我们将使用兔子的脊髓 缺血模型，其产生高度可再现的损伤， 对生物化学研究特别有价值。 这种模式也可以 作为一个非常敏感的生物测定系统，使我们能够测试是否 这种治疗方式可以改善神经功能。 拟议的研究是 旨在进一步确定导致缺血的分子机制 诱发神经功能丧失，以及可能有用的技术 开发新的方法来防止这种损失或恢复功能。

Several drugs have been shown to reduce neurologic damage in a variety of stroke models by the critical pharmacologic actions of the therapies have not been detailed in most instances. The search for therapies to prevent or minimize ischemic central nervous system injury has been hindered by inadequate fundamental understanding of the mechanisms of damage. This has been caused, in part, by models that are not well designed for correlating biochemical, pharmacological, and neurological function studies. There have been substantial recent advances in identification of trophic factors. These are proteins that have many actions including involvement in repair of injuries to various parts of the body. They are also present in the central nervous system. Some appear necessary for survival of neuronal populations, and there is reason to suspect they are involved in the responses to central nervous system injury. Several of these factors stimulate protein kinases, which are families of enzymes that function as second messengers in this chain of events. Protein kinases have been the focus of numerous important investigations over the past few years because their actions seem responsible for the primary activities of many cell types, especially in the nervous system. We hypothesize that disturbances of protein phosphorylation are a major cause of the onset of irreversible ischemic neurologic damage. Furthermore, we think that trophic factors can modify central nervous system damage, at least partly by their actions on protein phosphorylation. For these studies, we will use a rabbit spinal cord ischemia model which produces highly reproducible lesions that are particularly valuable for biochemical studies. This model can also be used as a very sensitive bioassay system to allow us to test whether a form of therapy improves neurologic function. The proposed studies are intended to further define the molecular mechanisms causing ischemia induced loss of neurologic function, and techniques that may be useful for developing new ways to prevent such losses or restore function.