Synaptic Damage and Plasticity After Brain Ischemia

脑缺血后的突触损伤和可塑性

• 批准号: 6678506
• 负责人: Bingren Hu
• 金额: $ 27.95万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6678506
• 关键词: biological signal transduction; brain cell; cAMP response element binding protein; cell morphology; central nervous system disorders; cerebral ischemia /hypoxia; computed axial tomography; electron microscopy; laboratory mouse; laboratory rat; mass spectrometry; nerve /myelin protein; nerve injury; neural plasticity; neurons; protein structure function; proteomics; synapses; tissue /cell culture; transient ischemic attack; two dimensional gel electrophoresis

DESCRIPTION (provided by applicant): The objective of this project is to investigate molecular mechanisms of synaptic damage and plasticity after transient cerebral ischemia (TCI). TCI selectively causes delayed neuronal death and leads to neurological deficits. Neurological functional recovery after stroke, which requires precise cell-to-cell communication through synapses, is a key issue for stroke patients. Therefore, studies of morphological and molecular alterations of synapses are relevant to understanding the mechanisms of ischemic neuronal loss and neurological outcome. However, very few studies on changes in synapses after ischemia have been conducted. We have recently established a series of techniques to study synaptic changes after brain insults, and found dramatic ultrastructural and biochemical alterations of synapses after TCI. The focus of the present proposal is to extend our previous studies and to propose new studies on synaptic remodeling after TCI. We will test a general hypothesis that progressive synaptic damage develops due both to damage induced by the ischemic event and to the lack of synaptic repair mediated by the ERK-CREB signaling cascade in ischemically vulnerable neurons after transient cerebral ischemia. The specific aims are: 1. To study the synaptic alterations in multiple brain regions after various ischemic durations. 2. To investigate molecular reorganization of synapses after ischemia. 3. To study the regulatory role of the ERK-CREB cascade in synaptic remodeling after ischemia. Synaptic transmission is a very plastic process that is regulated via morphological changes, biochemical modification and molecular remodeling. Severe brain insults can damage synapses and induce neurological dysfunction. Understanding synaptic plasticity and damage after ischemia are key to develop therapeutic interventions. In this application, we propose studies to investigate synaptic damage and plasticity after brain ischemia.

描述（由申请人提供）：该项目的目的是研究短暂性脑缺血（TCI）后突触损伤和可塑性的分子机制。 TCI有选择地导致延迟神经元死亡并导致神经系统缺陷。中风后的神经功能恢复（需要通过突触进行精确的细胞对电池通信）是中风患者的关键问题。因此，对突触的形态和分子改变的研究与了解缺血性神经元丧失和神经系统结果的机制有关。但是，很少有关于缺血后突触变化的研究。我们最近建立了一系列研究大脑侮辱后研究突触变化的技术，并发现TCI后突触的急剧超微结构和生化改变。本提案的重点是扩展我们以前的研究，并提出有关TCI后突触重塑的新研究。我们将检验一个普遍的假设，即由于缺血事件引起的损害和由于短暂性脑缺血后缺血性脆弱神经元中的ERK-CREB信号级联介导的突触修复而导致的渐进性突触损伤。具体目的是：1。研究各种缺血性持续时间后多个大脑区域的突触改变。 2。研究缺血后突触的分子重组。 3。研究ERK-CREB级联反应在缺血后的突触重塑中的调节作用。 突触传播是一种非常塑性的过程，可以通过形态变化，生化修饰和分子重塑来调节。严重的大脑侮辱会损害突触并引起神经功能障碍。了解缺血后的突触可塑性和损害是发展治疗干预措施的关键。在此应用中，我们建议研究脑缺血后研究突触损伤和可塑性。