BRAIN RECOVERY IN REVERSIBLE THROMBOTIC STROKE

可逆性血栓性中风的脑恢复

• 批准号: 3406507
• 负责人: BRANT D WATSON
• 金额: $ 17.16万
• 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 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3406507
• 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.

我们建议对大鼠进行可重复的血栓性中风， 并评估组织病理学、流变学和生理学 缺血期间和血管后组织状态的指标 再通的独特的溶栓剂，hementin。 的 特别感兴趣的是确定，在发作之后，时间 可以实现再通而不诱导 缺血性受损远端血管节段出血。 缺血后再灌注损伤的证据将在以下方面寻找： 氧自由基刺激的组织水肿中性粒细胞浸润 和脂质过氧化作用。 这些抑制的程度 组织破坏介质将在以下条件下进行检查 施用特异性靶向的淬灭剂，例如 稳定的前列环素类似物伊洛前列素，和酶促的 超氧自由基清除剂，超氧化物歧化酶， 短寿命（血浆中）铜/锌形式和独特的长寿命 锰形态 由于这些研究包括血栓性 脑卒中诱导期及恢复期的治疗 阶段，通过减轻几个有害方面的帮助， 在临床上，代谢受损脑组织的再灌注 可能会产生相关信息。 我们的血栓性中风模型是由光激发介导的 静脉注射虎红染料，或通过氩离子激光 大脑中动脉照射或氙弧灯照射 照射暴露的半透明头骨和下面的 皮质微血管 闭塞显示为白色血栓 含有凝集的血小板， 内皮受损 在hementin诱导的再通后， 临床相关时间（发作后6小时内）， 水肿将被测定为脑水含量，血流量由 14 C-碘安替比林技术，通过氧张力测定代谢状态， 钾离子活性和氢清除率，脂质过氧化 通过席夫碱自发荧光或共轭二烯，和 抗髓过氧化物酶染色法测定中性粒细胞含量， 抗体或铟标记。 根据这些指标， 再灌注损伤，抗氧化剂的改善作用 还将评估抗神经炎药物。 我们还将 研究光学方法以提高 光化学诱导的血管闭塞;这种发展是 预计将有利于大脑中新生血管的手术， 眼睛