Experimental Intracerebral Hemorrhage

实验性脑出血

• 批准号: 6540516
• 负责人: JUSTIN A. ZIVIN
• 金额: $ 24.5万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6540516
• 关键词: anticoagulants; blood pressure; cardiovascular pharmacology; cerebral hemorrhage; disease /disorder etiology; disease /disorder model; drug screening /evaluation; fibrinolytic agents; histopathology; ischemia; laboratory rabbit; laboratory rat; nerve injury; neuropharmacology; neuroprotectants; plasminogen; plasminogen activator; prostaglandin endoperoxide synthase; streptokinase; stroke

Intracerebral hemorrhage (ICH) causes approximately 10 percent of strokes. It is particularly important because younger stroke victims are commonly affected, and ICH hemorrhaging is the most feared complication of acute thrombolytic therapy, the only generally accepted treatment for ischemic stroke. We currently have no proven therapy for most types of ICH. Although tissue plasminogen therapy for stroke was FDA approved in 1996, at the present time, only about 2 percent of stroke victims in the United States receive this highly effective treatment. Thus, investigations of methods for reducing the damage caused by ICH should provide a basis for treating patients with primary ICH and protecting the much larger group of ischemic stroke victims. We propose to investigate both fundamental structural and biochemical abnormalities that cause ICH, and to develop pharmacological methods for reducing the extent of hemorrhaging and its secondary neurological consequences. We have already shown that several drugs that influence cerebral inflammatory responses to ICH can reduce both hemorrhaging and neurological damage in our ICH models. We also have preliminary data showing that histopathological and biochemical methods are valuable for investigating some of the causes of hemorrhaging. For these studies, we propose to employ a coordinated set of animal models that facilitate pharmacological and more basic studies. We propose to further define the types of neuroprotective drugs that reduce ICH induced neurological damage caused inflammatory reactions. We also plan to investigate the interactions between blood pressure, thrombolytic agents and ICH. This may provide insights as to how best to manage acute stroke victims. Finally, we intend to investigate the biochemical relationships between ICH and purely ischemic strokes using biochemical tools. These studies may provide insights about the causes of bleeding and neurological tissue damage that should be helpful in designing even more effective stroke therapies.

大约 10% 的中风是由脑出血 (ICH) 引起的。 这一点尤其重要，因为年轻的中风患者通常会受到影响，而脑出血是急性溶栓治疗最令人担心的并发症，而急性溶栓治疗是唯一普遍接受的缺血性中风治疗方法。 目前，我们还没有针对大多数类型脑出血的有效治疗方法。 尽管组织纤溶酶原治疗中风的疗法于 1996 年获得 FDA 批准，但目前，美国只有约 2% 的中风患者接受了这种高效的治疗。 因此，对减少 ICH 造成的损害的方法的研究应该为治疗原发性 ICH 患者和保护更多的缺血性中风患者提供基础。我们建议研究导致脑出血的基本结构和生化异常，并开发药理学方法来减少出血程度及其继发性神经系统后果。 我们已经证明，几种影响 ICH 脑炎症反应的药物可以减少 ICH 模型中的出血和神经​​损伤。 我们还有初步数据表明，组织病理学和生化方法对于研究一些出血原因很有价值。 对于这些研究，我们建议采用一套协调的动物模型，以促进药理学和更基础的研究。我们建议进一步定义神经保护药物的类型，以减少ICH引起的神经损伤引起的炎症反应。 我们还计划研究血压、溶栓剂和脑出血之间的相互作用。 这可能为如何最好地管理急性中风患者提供见解。 最后，我们打算使用生化工具研究 ICH 和纯粹缺血性中风之间的生化关系。 这些研究可能提供有关出血和神经​​组织损伤原因的见解，这有助于设计更有效的中风疗法。