NEUROPHYSIOLOGY OF HIPPOCAMPAL NEURONS AFTER ISCHEMIA

缺血后海马神经元的神经生理学

• 批准号: 2271676
• 负责人: ZAO C XU
• 金额: $ 9.44万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-20 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2271676
• 关键词: biotin; brain electrical activity; brain injury; cellular pathology; cerebral ischemia /hypoxia; hippocampus; histology; laboratory rat; membrane potentials; neural plasticity; single cell analysis; tissue /cell culture

DESCRIPTION (Investigator's Abstract): My long term goal is to identify mechanisms of neuronal damage following transient ischemia and provide a basis for evaluating potential treatment for postischemic injury in the CNS. Cerebrovascular disease (stroke) is one of the leading cause of death in the United States. Over 500,000 patients suffer the effects of hypoxic- ischemic' brain damage yearly. Excitotoxic effect of excessive glutamate release during ischemia has been postulated as one of the primary factors in postischemic neuronal damage. However, previous studies fail to provide a consistent picture of neuronal hyperactivity following ischemia with extracellular recording or brain slice preparations. Using in vivo intracellular recording and staining techniques, the objective of the proposed research is to elucidate' changes in neuronal and synaptic activity that occur in pyramidal neurons of rat hippocampus after transient forebrain ischemia, and to determine their roles in selective neuronal injury following- -ischemia. The main hypotheses to be tested are whether neuronal activity of CAl neurons is enhanced after transient ischemia, and whether such enhancement is due to a) enhanced synaptic transmission or b) increased intrinsic excitability of CAl neurons. Secondarily it will be determined whether neurophysiological changes differ in ischemia- sensitive CAl neurons and ischemia-resistant CA3 neurons following, ischemia, thereby identifying those factors that may contribute to the selective vulnerability of CAl neurons. Forebrain ischemia of 5-20 min duration will be induced using the 4-vessel occlusion method. Spontaneous activities and evoked potentials of CAl and CA3 neurons before, during, and at different intervals after transient ischemia will be compared to reveal the postischemic changes of neuronal activity and synaptic transmission. Changes in neuronal excitability will be studied by comparing membrane properties of the neuron before and after transient ischemia. Neurophysiological changes associated with selective neuronal injury will be determined by comparing the postischemic responses of CA I and CA3 neurons. The neurons in which the recordings are made will be identified by intracellular staining with neurobiotin. The proposed experiments will bridge the gap between previous extracellular recording studies of ischemia in vivo and intracellular recording studies of hypoxia/ ischemia in vitro. The results of this study will improve understanding of the mechanisms of brain damage upon resuscitation following cardiac arrest.

描述（研究者的摘要）：我的长期目标是确定 短暂缺血后神经元损伤的机制，并提供 评估潜在治疗后缺血后损伤的基础 中枢神经系统。 脑血管疾病（中风）是主要原因之一 在美国死亡。超过500,000名患者遭受影响 每年低氧缺血性脑损伤。兴奋性毒性的作用 缺血期间过多的谷氨酸释放已被认为是一个 缺血后神经元损伤的主要因素。然而， 先前的研究无法提供神经元的一致图片 缺血后的多动症，细胞外记录或大脑 切片准备。使用体内细胞内记录和染色 技术，拟议的研究的目的是阐明' 锥体中发生的神经元和突触活动的变化 短暂前脑缺血后大鼠海马的神经元，至 确定它们在 - 缺血后选择性神经元损伤中的作用。 要测试的主要假设是CAL的神经元活性是否 短暂性缺血后神经元得到增强，是否 增强是由于a）增强的突触传播或b）增加 Cal神经元的内在兴奋性。 其次是 确定缺血的神经生理变化是否有所不同 敏感的CAL神经元和抗缺血的CA3神经元之后， 缺血，从而确定可能有助的因素 Cal神经元的选择性脆弱性。 前脑缺血为5-20分钟 持续时间将使用4-PESSEL闭塞法诱导。自发的 在，在，期间，期间， 并将短暂性缺血后的不同时间间隔比较 揭示神经元活性和突触的缺血后变化 传播。神经元兴奋性的变化将通过 比较瞬态前后神经元的膜特性 缺血。与选择性神经元有关的神经生理变化 受伤将通过比较CA的缺血后反应来确定 我和Ca3神经元。记录的神经元将是 通过神经益素的细胞内染色鉴定。 提议 实验将弥合先前细胞外记录之间的差距 缺血性缺血和缺氧/缺乏的细胞内记录研究 体外缺血。这项研究的结果将提高对 心脏骤停后复苏后脑损伤的机制。