BRAIN RECOVERY IN REVERSIBLE THROMBOTIC STROKE

可逆性血栓性中风的脑恢复

• 批准号: 3406511
• 负责人: BRANT D WATSON
• 金额: $ 14.88万
• 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/3406511
• 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.

我们建议对大鼠实施可复制的血栓性中风， 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示物 使用独特的溶栓剂--氯化血红素进行再通。的 尤其令人感兴趣的是，在《伊卡特斯》之后，确定时间 无需诱导即可实现再通畅的领域 缺血损害的远端血管节段出血。 将从以下方面寻找缺血后再灌注损伤的证据 氧自由基致组织水肿，中性粒细胞浸润 和脂质过氧化。对这些的抑制程度 下面将检查组织破坏的介体 给予特定靶向的猝灭剂，如 稳定的前列环素类似物伊洛前列素及其酶制剂 超氧阴离子自由基清除剂，超氧化物歧化酶 短寿命(等离子体)铜/锌形式和独特的长寿命 锰的形态。因为这些研究包括血栓形成 卒中诱导期及其恢复期的治疗 阶段，由于减轻了几个有害方面的影响 临床表现为代谢受损的脑组织再灌流 可能会产生相关信息。 我们的血栓性卒中模型是通过光激发 静脉注射玫瑰色孟加拉染料，要么用Ar离子激光 大脑中动脉照射或氙弧灯照射 照射暴露的半透明的头骨和下面的 皮质微血管构筑。闭塞(S)在中显示为白色血栓 含有凝集的血小板对光化学的响应 内皮受损。在血红素诱导的血管再通后 临床相关时间(发病后不到6小时)， 水肿将通过脑含水量、血流量等指标进行检测 ~(14)C-安替比林技术，氧分压测定代谢状态， 钾离子活性与氢清除、脂质过氧化 通过席夫碱自体荧光或共轭双烯，以及 抗髓过氧化物酶染色和荧光法测定中性粒细胞含量 抗体或铟标记。就这些指标而言， 再灌注损伤，抗氧化剂的改善作用 还将对抗中性粒细胞药物进行评估。我们还将 研究提高效率的光学方法 光化学诱导的血管闭塞；这一进展是 预计将有利于脑部新生血管的外科手术 眼睛。