NEUROPHYSIOLOGY OF STRIATAL NEURONS AFTER ISCHEMIA

缺血后纹状体神经元的神经生理学

• 批准号: 6363926
• 负责人: ZAO C XU
• 金额: $ 14.69万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6363926
• 关键词: cerebral ischemia /hypoxia; corpus striatum; dopamine; dopamine receptor; hippocampus; interneurons; laboratory rat; neural degeneration; neural transmission; neurons; neurophysiology; pathologic process; synapses

DESCRIPTION: (Applicant's abstract) Cerebrovascular disease (stroke) is the third leading cause of death, and the number one cause of disability in the United States. The applicant's long-term goal is to identify mechanisms of neuronal damage following transient cerebral ischemia CA1 neurons in hippocampus and spiny neurons in neostriatum are highly vulnerable to transient forebrain ischemia. The current knowledge about the pathogenesis of post-ischemic neuronal injury is mainly derived from studies on hippocampal neurons. Little is known about the neurophysiological changes in striatal about the neurophysiological changes of striatal neurons following ischemia. The temporal threshold for injury and the time course of cell loss differ dramatically between hippocampus and neostriatum. The mechanisms underlying the neuronal injury in these two regions may not be the same. Studies have shown that the synaptic transmission of CA1 neurons enhances after lethal ischemia. It has also been shown that depletion of dopamine neurons dramatically reduces the post-ischemic neuronal damage in neostriatum. The working hypothesis of this proposal is that dopamine neurons dramatically reduces the post-ischemic neuronal damage in neostriatum. The working hypothesis of this proposal is that dopamine aggravates the post-ischemic neuronal injury by potentiating glutamate excitoxicity. The experiments in this proposal are designed to determine: 1) Whether the synaptic transmission of spiny neurons if facilitated after ischemia and thereby cause neuronal injury; 2) How dopamine potentiates the synaptic transmission and aggravates the neuronal damage after ischemia. The specific aims of the proposed experiments are: To compare the synaptic transmission of spiny neurons in neostriatum before and after 22 min forebrain ischemia. 2. To study the synaptic transmission of interneurons in neostriatum before and after 22 min ischemia and compare with that of spiny neurons. 3. To analyze the post- ischemic neurophysiological changes of spiny neurons after dopamine depletion and compare with those in intact neostriatum. 4. To determine the mechanisms of asymmetrical protection of striatal neurons against ischemia after dopamine depletion. The results of the proposed experiments will identify the electrophysiological changes correlated with the selective neuronal injury in neostriatum following forebrain ischemia and improve our understanding of the mechanism of brain damage upon resuscitation following cardiac arrest.

描述：（申请人的摘要）脑血管疾病（中风）是 死亡的第三个主要原因和残疾的第一原因 在美国。申请人的长期目标是确定 短暂脑缺血CA1后神经元损伤的机制 海马中的神经元和新纹状体中的棘神经元高度 容易受到短暂性前脑缺血的影响。当前关于 缺血后神经元损伤的发病机理主要源自 海马神经元的研究。关于 神经生理学的纹状体神经生理变化 缺血后纹状体神经元的变化。时间阈值 受伤和细胞损失的时间过程在 海马和新纹状体。神经元损伤的基础机制 在这两个区域中可能不一样。研究表明 CA1神经元的突触传播增强致死性缺血后。它 还显示了多巴胺神经元的耗竭 减少了新纹状体中缺血后神经元损伤。工作 该提议的假设是多巴胺神经元大大降低 新纹状体中缺血后神经元损伤。工作假设 该提议是多巴胺加剧了缺血后神经元 通过增强谷氨酸兴奋性来损伤。其中的实验 建议旨在确定：1）突触传播是否 如果缺血后促进刺神经元，从而导致神经元 受伤; 2）多巴胺如何增强突触传播和 缺血后加重神经元损害。特定目标 建议的实验是： 比较新纹状体中棘神经元的突触传播 前后22分钟前脑缺血。 2。研究突触 22分钟之前和之后，新纹状体中的神经元传播 缺血并与棘神经元的缺血相比。 3。分析后 多巴胺后棘神经元的缺血性神经生理变化 耗尽并与完整的新纹状体相比。 4。确定 纹状体神经元不对称保护的机理 多巴胺消耗后的缺血。提出的实验的结果 将确定与 前脑缺血后，新纹状体的选择性神经元损伤和 提高我们对脑损伤机制的理解 心脏骤停后的复苏。