ADENOSINE AND THE NEURONAL RESPONSE TO HYPOXIA/ISCHEMIA

腺苷和神经元对缺氧/缺血的反应

• 批准号: 6394188
• 负责人: JOHN C FOWLER
• 金额: $ 17.47万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394188
• 关键词: adenosine; adenosine deaminase; adenosine kinase; brain disorder chemotherapy; carotid artery; cerebral ischemia /hypoxia; disease /disorder model; electroencephalography; free radical oxygen; free radical scavengers; hippocampus; intraarterial administration; laboratory rat; neural transmission; neuropharmacology; oxygen; purinergic receptor; transient ischemic attack

DESCRIPTION: (Verbatim from the Applicant's Abstract) The long-term goal of this research is to understand the (patho) physiologic role of the inhibitory neuromodulator adenosine in the brain's early resp0onse to stroke. Understanding adenosine's contribution is important because adenosine-based pharmacological interventions show promise in reducing neuronal hypoxic/ischemic injury in a number of animal models [31,34,83,87,117]. The specific focus if this proposal is to extend to an in vivo model of the PI's previous series of studies performed in the in vitro hippocampal slice. These in vitro studies detailed adenosine's substantial mediation of the early reversible depression of synaptic transmission and adenosine's interaction with the anoxic depolarization in response to ischemic-like conditions [39-42,44]. Surprisingly, in spite of an extensive literature describing adenosine's role I in vitro slice preparations [9,24,52,69,89,90,142], there has yet to be, to the best of our knowledge, a demonstration of adenosine's role in vivo. The following specific aims, therefore, focus on examining the contribution of salient observations made in vitro to an in vivo hypoxic/ischemic rat hippocampal model. The following specific aims will be addressed: Specific Aim 1. Determine the role of adenosine receptors in the in the early hypoxic/ischemic depression of synaptic transmission in vivo. Specific Aim 2. Examine the relationship between adensone receptor activation, inhibition of evoked synaptic potentials and tissue pO2 in vivo. Specific Aim 3. Determine the influence of adenosine receptor activation on development of the anoxic depolarization during extended hypoxia/ischemia in vivo. And, examine adenosine receptor function in the post-ischemic period after the anoxic depolarization.

描述：（逐字摘自申请人摘要）长期目标 这项研究旨在了解抑制性的（病理）生理作用 神经调节剂腺苷在大脑对中风的早期反应中的作用。 了解腺苷的贡献很重要，因为基于腺苷的 药物干预有望减少神经元 许多动物模型中出现缺氧/缺血性损伤[31,34,83​​,87,117]。 如果该提案要扩展到体内模型，则具体重点是 PI之前的一系列研究是在体外海马切片中进行的。 这些体外研究详细说明了腺苷对早期 突触传递的可逆性抑制以及腺苷与 响应缺血样条件的缺氧去极化[39-42,44]。 令人惊讶的是，尽管有大量文献描述了腺苷的作用，但我 体外切片制剂[9,24,52,69,89,90,142]，目前还没有， 据我们所知，这证明了腺苷在体内的作用。这 因此，遵循具体目标，重点审查 在体外对体内缺氧/缺血大鼠进行的显着观察 海马模型。 将实现以下具体目标： 具体目标 1. 确定腺苷受体在早期的作用 体内突触传递的缺氧/缺血抑制。 具体目标 2. 检查腺苷受体激活、 抑制体内诱发突触电位和组织 pO2。 具体目标 3. 确定腺苷受体激活对 长期缺氧/缺血期间缺氧去极化的发展 体内。并且，检查缺血后时期的腺苷受体功能 缺氧去极化后。