Estradiol Regulation of Brain-Microvascular Inflammatory Responses in Sepsis

雌二醇对脓毒症脑微血管炎症反应的调节

• 批准号: 9035982
• 负责人: Candice Brown
• 金额: $ 14.28万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9035982
• 关键词: Estradiol; Regulation; Brain; Microvascular; Inflammatory

DESCRIPTION (provided by applicant): The objective of this K01 proposal is to establish an innovative research strategy and sound career development plan for Dr. Candice Brown to successfully transition to an independent investigator in neuroscience. The research plan implements a novel, multidisciplinary approach to test the hypothesis that the ovarian estrogen, 17�-estradiol (E2), modifies sepsis-induced brain dysfunction by altering the inflammatory mechanisms at the brain-micro vascular interface. The experimental approach uses a cecal ligation and puncture model of sepsis-induced brain dysfunction, commonly referred to sepsis-associated encephalopathy (SAE). SAE results in neurological impairment in ~70% of sepsis patients, and therapeutic options for treatment are limited. Aim 1 will employ intravital microscopy combined with molecular biology to determine whether E2 attenuates vascular inflammation at the brain-micro vascular interface. Aim 2 will use magnetic resonance imaging combined with immunocytochemistry to determine whether E2 attenuates cerebral edema and metabolic dysfunction in the early and late stages of sepsis. The career development plan has four specific aims designed to achieve short and long term career goals. These include: 1) Mastering surgical techniques and microscopy imaging tools; 2) Acquiring competency in MRI and its capabilities to use as tool to study acute brain dysfunction; 3) Improving presentation, publication, and craftsmanship skills, and 4) Gaining faculty development skills to become a productive science-citizen in academia. Completion of Research and Career Aims will provide broad competencies and a valuable set of tools to establish a productive independent research program and enhance the diversity of the neuroscience community at Wake Forest School of Medicine.

描述（由应用程序提供）：该K01提案的目的是为Candice Brown博士建立创新的研究策略和合理的职业发展计划，以成功地过渡到神经科学的独立研究者。该研究计划实施了一种新型的多学科方法，以检验卵巢雌激素17-雌二醇（E2）通过改变脑微神经血管界面的炎症机制来改变败血症诱导的脑功能障碍的假设。实验方法使用败血症引起的脑功能障碍的盲肠结扎和穿刺模型，通常称为败血症相关的脑病（SAE）。 SAE导致约70％的败血症患者的神经系统损害，治疗方法受到限制。 AIM 1将采用内插入显微镜结合分子生物学来确定E2在AIM 2处减轻血管炎症2将使用磁共振成像与免疫细胞化学相结合，以确定E2是否会减轻SEPESIS早期和后期的脑性质和代谢功能障碍。职业发展计划具有四个特定的目标，旨在实现短期和长期的职业目标。其中包括：1）掌握手术技术和显微镜成像工具； 2）获得MRI的能力及其用作研究急性脑功能障碍的工具的能力； 3）改进的演讲，出版和工艺技巧，以及4）获得教师发展技能，成为学术界的一名富有成效的科学意见。研究和职业目标的完成将提供广泛的能力和一套宝贵的工具，以建立生产性独立研究计划，并在Wake Forest医学院增强神经科学社区的多样性。