Experimental Intracerebral Hemorrhage

实验性脑出血

• 批准号: 6613803
• 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/6613803
• 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.

脑出血（ICH）导致约10%的中风。 这一点尤其重要，因为年轻的中风患者通常受到影响，而ICH栓塞是急性溶栓治疗最可怕的并发症，是缺血性中风唯一普遍接受的治疗方法。 目前，我们还没有针对大多数类型ICH的有效疗法。 虽然组织纤溶酶原疗法在1996年被FDA批准用于中风，但目前，在美国只有大约2%的中风患者接受这种高效的治疗。 因此，研究减少脑出血引起的损害的方法应该为治疗原发性脑出血患者和保护更大的缺血性卒中患者群体提供基础。我们建议调查导致ICH的基本结构和生化异常，并开发药理学方法来减少脑出血的程度及其继发的神经系统后果。 我们已经证明，在我们的ICH模型中，几种影响脑出血炎症反应的药物可以减少脑出血和神经损伤。 我们也有初步的数据显示，组织病理学和生物化学方法是有价值的调查的一些原因，复发。 对于这些研究，我们建议采用一组协调的动物模型，以促进药理学和更基础的研究。我们建议进一步确定神经保护药物的类型，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、溶栓药物和ICH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和单纯缺血性卒中之间的生化关系。 这些研究可能会提供有关出血和神经组织损伤原因的见解，这将有助于设计更有效的中风治疗方法。