CALCIUM BLOCKER & RELATED THERAPY FOR CEREBRAL ISCHEMIA

钙阻滞剂

• 批准号: 2265034
• 负责人: JAMES C GROTTA
• 金额: $ 28.78万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265034
• 关键词: active sites; animal mortality; blood flow measurement; calcium channel blockers; calcium flux; calmodulin; calmodulin dependent protein kinase; cerebral ischemia /hypoxia; drug metabolism; drug screening /evaluation; enzyme mechanism; glutamates; glycine; histology; human subject; human therapy evaluation; immunocytochemistry; inhibitor /antagonist; laboratory rat; learning; microscopy; phospholipase inhibitor; transferase

DESCRIPTION (Adapted from the applicant's abstract): This research proposal is a re-submission of a research project that was submitted as a competitive renewal. The long-term objective of this research proposal is to evaluate and understand potential pharmacotherapies for acute cerebral ischemia so that appropriate drugs might be tested which will reduce or prevent calcium entry into neurons or its consequences. Therapies that will be directed at this will include selected calcium channel blockers, competitive and non-competitive glutamate antagonists, phospholipase antagonists, and possibly newer agents which may act on glycine or sigma sites. Outcome measures will include mortality, light microscopic measurement of ischemic damage, and learning ability. Mechanisms of action of each pharmacotherapy will be determined by cerebral blood flow, immunocytochemical localization and quantitation of calcium calmodulin binding and assessment of CaM-kinase II activity. The second major goal of this research is to expand previous studies of calcium calmodulin binding after global ischemia to better understand calcium activated events in determining irreversible neuronal injury. Studies will be designed to correlate calcium calmodulin binding studies with CaM Kinase II activity and explore the behavior of this kinase after various ischemic intervals.

描述（改编自申请人摘要）：本研究 提案是重新提交的研究项目，该项目是作为 竞争性更新。 这项研究计划的长远目标是 评估和了解急性脑梗死的潜在药物治疗 缺血，以便测试适当的药物，这将减少或 防止钙进入神经元或其后果。 的疗法 将针对这一点将包括选定的钙通道阻滞剂， 竞争性和非竞争性谷氨酸拮抗剂，磷脂酶 拮抗剂，以及可能作用于甘氨酸或西格玛的较新药物 网站. 结局指标将包括死亡率、光镜检查 缺血性损伤和学习能力的测量。 作用机制 将通过脑血流量来确定每种药物治疗的有效性， 钙调素免疫细胞化学定位和定量 结合和评估CaM-激酶II活性。 第二大目标 本研究是对以往钙-钙调素结合研究的拓展 为了更好地了解全脑缺血后的钙激活事件， 确定不可逆的神经元损伤。 研究的目的是 将钙/钙调素结合研究与CaM激酶II活性相关联 并探索这种激酶在不同缺血间隔后的行为。