ALTERED CALCIUM HOMEOSTASIS IN POSTISCHEMIC NEURON DEATH

缺血后神经元死亡中钙稳态的改变

• 批准号: 2685746
• 负责人: John A Connor
• 金额: $ 27.74万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2685746
• 关键词: NMDA receptors; calcium channel; calcium flux; cell death; cerebral ischemia /hypoxia; digital imaging; electrophysiology; gerbil /jird; glutamates; hippocampus; homeostasis; immunocytochemistry; immunofluorescence technique; neurons; pyramidal cells; tissue /cell preparation; voltage gated channel

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.

描述 大脑中特定的重要神经元会受到延迟死亡的影响 在中风时发生的短暂的血流中断之后， 外伤或心脏骤停 虽然许多神经元被直接杀死， 由于缺血性损伤，这些群体在几个月的时间内遭受损耗， 在这段时间里，它们保留了许多正常的信号功能。 其中一些人口容易延迟死亡，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 因为他们了解了他们所经历的相当漫长的死亡程序。 如果是这样的话，康复的财政和社会费用不断增加， 支持这些事件的幸存者，在一个老龄化的国家， 人口可能会减少。 很多证据，有些是间接的， 表明细胞内Ca2+水平的严重破坏 是延迟性神经元死亡的直接触发因素， 缺血后神经元调节Ca2+能力的后续变化 应该是近端死因 这里的建议是一个 直接研究：1）CA 1细胞内钙调节 体内受到缺血性损伤的海马神经元，以及 2)正常神经元在缺血或缺血后数小时内的钙变化， 体外兴奋性毒性损伤。 数字成像和荧光技术， 许多在这个实验室开发的，将用于监测钙离子， 单个神经元和神经元组响应生理 刺激. 虽然有大量的文献基于对 组织培养中的神经元，很少有关于缺血后 已经通过直接测量神经元来检查钙调节， 已经在体内条件下发展并受到损伤。