CALCIUM BLOCKER & RELATED THERAPY FOR CEREBRAL ISCHEMIA

描述(改编自申请人的摘要)：这项研究 提案是重新提交的研究项目，该项目是作为 竞争性更新。这项研究提案的长期目标是 评估和了解急性脑部疾病的潜在药物治疗 缺血，因此可能会测试适当的药物，从而减少或 防止钙离子进入神经元或其后果。治疗方法 将针对这一点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。结果指标将包括死亡率、光镜检查 测量缺血损伤和学习能力。行动机制 每种药物治疗的效果将由脑血流决定， 钙调素的免疫细胞化学定位和定量 钙调素-激酶II的结合和活性评估。第二个主要目标是 本研究旨在拓展前人对钙调素结合的研究 全脑缺血后更好地了解钙激活事件 确定不可逆转的神经元损伤。研究将被设计为 钙调素结合研究与CaM-Kinase II活性的相关性 并探讨该激酶在不同缺血间隔后的行为。

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.