BRAIN RECOVERY IN REVERSIBLE THROMBOTIC STROKE

可逆性血栓性中风的脑恢复

• 批准号: 3406512
• 负责人: BRANT D WATSON
• 金额: $ 15.62万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3406512
• 关键词: allopurinol; anticoagulants; antioxidants; artificial intelligence; brain edema; calcium channel blockers; cardiovascular pharmacology; cerebral ischemia /hypoxia; diene; electron microscopy; fibrinolytic agents; histopathology; laboratory rat; lipid peroxides; neutrophil; perfusion; photochemistry; physiology; plasminogen activator; platelet aggregation; platelet aggregation inhibitors; prostacyclins; singlet oxygen; stroke; superoxide dismutase; thrombosis; tissue /cell culture

We propose to administer reproducible thrombotic stroke to rats, and to assess histopathologic, rheologic and physiological indicators of tissue status during ischemia and following vascular recanalization by the unique thrombolytic agent, hementin. Of particular interest is to determine, following the ictus, the time domain for which recanalization can be achieved without inducing hemorrhage from ischemically compromised distal vascular segments. Evidence of postischemic reperfusion injury will be sought in terms of oxygen radical-stimulated tissue edema, neutrophil infiltration and lipid peroxidation. The degree of inhibition of these mediators of tissue destruction will be examined following administration of specifically targeted quenching agents, such as the stable prostacyclin analog iloprost, and the enzymatic scavenger of superoxide radical, superoxide dismutase in both the short-lived (in plasma) copper/zinc form and the unique long-lived manganese form. Inasmuch as these studies encompass thrombotic stroke in the induction phase and its therapy in the recovery phase, as aided by mitigation of several deleterious aspects of reperfusion in metabolically compromise brain tissue, clinically relevant information may result. Our models of thrombotic stroke are mediated by photoexcitation of intravenously injected rose bengal dye, either by argon ion laser irradiation of the middle cerebral artery, or by xenon arc lamp irradiation of the exposed, translucent skull and the underlying cortical microvasculature. Occlusion(s) appear in as white thrombi containing agglutinated platelets in response to photochemically damaged endothelium. Following hementin-induced recanalization at clinically relevant times (less than 6 hours following the ictus), edema will be assayed as brain water content, blood flow by the 14C-iodoantipyrine technique, metabolic status by oxygen tension, potassium ion activity and hydrogen clearance, lipid peroxidation by Schiff-base autofluorescence or conjugated dienes, and neutrophil content by antimyeloperoxidase staining, and fluorescent antibody or indium labeling. In terms of these indicators of reperfusion injury, the ameliorating effect of the antioxidative and antineutrophil agents will also be assessed. We will also investigate optical means to improve the efficiency of photochemically induced vascular occlusion; this development is projected to benefit surgery of neovasculature in the brain and eye.

我们建议给大鼠可重复可重复的血栓性中风 并评估组织病理学，流变和生理学 缺血期间和血管后的组织状态指标 独特的溶栓剂绿色蛋白重新定性。 的 特别的兴趣是在ICTUS之后确定时间 可以在不诱导的情况下实现重新定性的域 远端远端血管段出血。 缺血后再灌注损伤的证据将以术语寻求 氧自由基刺激的组织水肿，中性粒细胞浸润 和脂质过氧化。 这些抑制程度 将检查组织破坏的介体 给予特定针对的淬火剂，例如 稳定的前列环素类似物依芦素和酶促的 在这两个 短暂的（等离子体）铜/锌形式和独特的长寿 锰的形式。 这些研究包括血栓形成 诱导阶段的中风及其恢复治疗 阶段，通过缓解几个有害方面的帮助 在代谢上损害脑组织的再灌注，临床上 可能会导致相关信息。 我们的血栓性中风模型是通过光激发的 静脉注射的玫瑰孟加拉染料，由氩离子激光器 脑中动脉的辐照或Xenon Arc Lamp 曝光，半透明的头骨和下面的辐照 皮质微举行。 闭塞以白色血栓形式出现 响应光化学的凝聚力血小板 受损的内皮。 在绿蛋白诱导的重新定性之后 临床相关时间（ICTUS之后少于6个小时）， 水肿将被分析为脑含水，血液流动 14C-碘胺技术，氧气张力的代谢状态， 钾离子活性和氢气清除，脂质过氧化 通过Schiff-Base自动荧光或共轭二烯，以及 抗氧化酶染色和荧光的中性粒细胞含量 抗体或依赖性标记。 根据这些指标 再灌注损伤，抗氧化剂的改善作用 并还将评估抗营养剂。 我们也会 调查光学手段以提高效率 光化学诱导的血管阻塞；这种发展是 预计将受益于大脑中新生血管的手术 眼睛。