ALTERED CALCIUM HOMEOSTASIS IN POSTISCHEMIC NEURON DEATH

描述 大脑中特定和重要的神经元容易延迟性死亡 在中风后短暂的血液流动中断之后，头部 创伤或心脏骤停。当许多神经元被直接杀死时 缺血性侮辱，这些人口在几年的时间里遭受磨损 在这段时间里，它们保留了许多正常的信号功能。 其中一些易受迟发性死亡的种群，如 海马体被认为是学习和记忆的重要部分 大脑的回路。这些神经元有可能被拯救 考虑到他们所经历的相当漫长的死亡计划。 如果是这样的话，不断增加的康复和社会成本 对这些事件的幸存者的支持，随着老龄化的增加 人口，可能会减少。有很多证据，有些是间接的， 会聚表明细胞内钙离子水平严重紊乱 是延迟性神经元死亡程序的直接触发因素 缺血后神经元调节钙离子能力的后续变化 都是死因的近端。这里的建议是一个 1)CA1细胞内钙调节的直接研究 在活体内受到缺血损伤的海马神经元，以及 2)脑缺血或缺血后数小时内正常神经元的钙变化 体外兴奋毒性侮辱。数字成像和荧光技术， 许多在这个实验室开发的，将被用来监测钙离子 单个神经元和成组神经元对生理性反应 刺激。尽管有大量的文献是基于对 组织培养中的神经元，几乎没有关于缺血后的基本猜测 钙调节已经通过直接测量神经元中的 都是在活体条件下发展和受伤的。

DESCRIPTION Specific and important neurons in the brain are subject to delayed death following short periods of blood flow disruption as occurs in stroke, head trauma, or cardiac arrest. While many neurons are killed outright by the ischemic insult, these populations suffer attrition over a period of several days, retaining many of their normal signaling functions during that time. Some of these populations vulnerable to delayed death, such as area CA1 of the hippocampus, are considered to be vital parts of the learning and memory circuitry of the brain. It is possible that these neurons could be rescued given an understanding of the rather drawn out death program they undergo. If so, the increasing financial and social costs of rehabilitation and support of survivors of these incidents, an increasing number in an aging population, might be reduced. Many lines of evidence, some indirect, converge to indicate that severe disruptions in intracellular Ca2+ levels are the immediate trigger for the delayed neuronal death program and that subsequent changes in the ability of post-ischemic neurons to regulate Ca2+ properly are the proximal cause of death. The proposal here is a straightforward investigation of 1) intracellular calcium regulation in CA1 neurons of the hippocampus that have been given ischemic insult in vivo, and 2) of the calcium changes in normal neurons within hours of an ischemic or excitotoxic insult in vitro. Digital imaging and fluorescence techniques, many developed in this laboratory, will be used to monitor Ca2+ in individual neurons and in groups of neurons responding to physiological stimulation. Although there is an extensive literature based on studies of neurons in tissue culture, few of the basic guesses regarding post-ischemic calcium regulation have been examined by direct measurement in neurons that have developed and been injured under in vivo conditions.