Defining targets for the treatment of delayed cerebral vasospasm after SAH

确定SAH后迟发性脑血管痉挛的治疗目标

• 批准号: 9165688
• 负责人: Jose Javier Provencio
• 金额: $ 32.2万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-11-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9165688
• 关键词: Defining; targets; treatment; delayed; cerebral

DESCRIPTION (provided by applicant): The goal of this research proposal is to investigate the role of neutrophils in the development of delayed neurologic deterioration (DND) after subarachnoid hemorrhage (SAH). The research strategy utilizes a novel and unique mouse model of SAH and a newly described inducible CXCR2 knockout mouse. The model of SAH was developed during funding from an NIH scientist development grant (K08) mechanism. The overall hypothesis is that the development of DND is mediated by recruited neutrophils entering the CNS after SAH and from neutrophil effector mechanisms once in the CNS. Performance of this research will advance current knowledge in three ways: 1) It will characterize the specific neuronal changes developed during SAH and determine the role of neutrophils in neuronal injury. It will clarify the role of the recruited neutrophil population in the development of DND tat is critical to understanding whether prevention of neutrophil entry into the CNS after SAH will be a target for treatment, and SAH. And finally it will help answer the question of whether medications administered after SAH that block neutrophils will be useful to treat DND. The Specific Aims are: 1: We will define the role of neutrophils in neuronal damage after SAH.. 2: We will reconstitute migration and effector function-competent neutrophils in CXCR2 deficient mice at multiple time points AFTER SAH to define the role of the recruited neutrophils in DND. 3: We will deplete neutrophils at time points after the SAH to define the critical times for neutrophil damage in SAH. This knowledge will identify targets for treatment in SAH and DND.

描述（由申请人提供）：这项研究建议的目的是研究中性粒细胞在蛛网膜下腔出血（SAH）后延迟神经系统恶化（DND）发展中的作用。该研究策略利用了SAH的新型小鼠模型和新描述的诱导CXCR2敲除小鼠。 SAH的模型是在NIH科学家发展赠款（K08）机制的资金中开发的。总体假设是，DND的发育是由SAH后进入中枢神经系统的招募中性粒细胞和中性粒细胞效应子机制介导的。这项研究的表现将以三种方式提高当前知识：1）它将表征SAH期间发生的特定神经元变化，并确定中性粒细胞在神经元损伤中的作用。它将阐明招募的中性粒细胞种群在DND TAT发展中的作用对于了解预防中性粒细胞在SAH之后进入中枢神经系统是否成为治疗目标和SAH至关重要。最后，这将有助于回答以下问题：SAH后是否服用药物，该障碍中性粒细胞对治疗DND有用。具体目的是：1：我们将在SAH后定义中性粒细胞在神经元损伤中的作用。2：我们将在SAH后在多个时间点重新建立CXCR2缺乏小鼠的迁移和效应功能功能功能功能，以定义DND中招募的中性粒细胞的作用。 3：我们将在SAH之后的时间点耗尽嗜中性粒细胞，以定义SAH中嗜中性粒细胞损害的关键时期。这些知识将确定在SAH和DND中的治疗目标。