STROKE THERAPY MECHANISMS WITH NEUROTROPHIC FACTORS

有几种药物被证明可以在不同方面减少神经损伤。 治疗的关键药理作用对卒中模型的影响 在大多数情况下都没有详细说明。寻找治疗方法 预防或最大限度地减少缺血性中枢神经系统损伤 由于对这一机制的基本认识不足而受阻 损坏。这在一定程度上是由不太好的模式造成的 设计用于将生化、药理学和神经学联系起来 机能研究。 最近在营养物质的鉴定方面取得了实质性的进展 各种因素。这些蛋白质有许多作用，包括参与 用于修复身体不同部位的损伤。他们也是 存在于中枢神经系统。其中一些似乎是必要的 神经元种群的生存，有理由怀疑它们是 参与中枢神经系统损伤的反应。其中几个 这些因素刺激蛋白激酶，这是酶的家族。 它在这一系列事件中扮演着第二信使的角色。蛋白 激酶一直是许多重要研究的焦点。 因为他们的行为似乎要为初选负责 多种细胞的活动，尤指神经系统中的活动。 我们假设蛋白质磷酸化的紊乱是一个主要的 不可逆性缺血性神经损伤的发病原因。 此外，我们认为营养因子可以修饰中枢神经。 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，我们将使用兔脊髓 缺血模型，可产生高度可重复性的损伤 对生化研究特别有价值。该型号还可以 作为一种非常灵敏的生物检测系统，使我们能够测试 这种疗法可以改善神经功能。建议进行的研究包括 旨在进一步确定导致缺血的分子机制 诱发的神经功能丧失，以及可能有用的技术 用于开发防止此类损失或恢复功能的新方法。

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.