West Virginia University Stroke COBRE

项目摘要。 WVU Stroke CoBRE的总体目标是降低与卒中相关的发病率和死亡率 通过提高对中风病理生理机制的理解。我们会完成的 总体目标是通过开展高质量的基础和转化研究，解决可改变的风险因素， 生物标志物、机制、预防策略、急性和慢性治疗以及中风康复。 要实现这一目标，必须实现以下三个具体目标：具体目标1。扩大 进行中风康复研究的受资助研究人员的临界质量。在第二阶段，我们建议巩固 研究人员对中风研究的承诺，部分是通过提供尖端的中风研究核心， 设施和服务，产生有意义的初步数据，以支持他们的赠款申请， 每年为5个早期职业调查员项目提供资金， 改善他们的赠款申请，并扩大在第一阶段开始的密集辅导计划， 西弗吉尼亚大学中风科布里。具体目标2。加强支撑和推进基础设施建设的创新科学核心 和平移中风研究。我们建议扩大 这些重要的核心。这将通过引入新的服务来实现（例如，新的中风模型; 额外的行为测试），并为研究核心提供培训课程。除了实验 中风核心（ESC）和啮齿动物行为核心（RBC），这是建议为COBRE资金，我们将 开发两个额外的核心，线粒体功能评估核心（MFAC）和中风组织 银行具体目标3。推动独立、可持续、多学科的 中风研究专题计划。实现WVU Stroke CoBRE独立的目标， 已经开始并将在第二阶段继续，过渡到以用户付费为基础的研究核心服务资金， 独立资助研究赠款金，包括为这些核心服务提供资金，以及 西弗吉尼亚大学健康科学学院。在WVU中风CoBRE第二阶段结束时， 将提供额外的早期职业调查人员参与中风相关研究。我们将 已经解决了对病因、急性和亚急性治疗的基础和转化研究的需求 通过（1）增加独立资助的西弗吉尼亚大学中风研究人员的数量，（2） 扩大中风研究的核心服务和用户数量，以及（3）继续过渡，以维持这些 通过基于用户的资助模式在西弗吉尼亚大学的服务资源。 拟议的WVU中风CoBRE研究补充与所有三个WVU中风CoBRE保持一致 的目的，并预计将增加家长奖的影响，促进前沿研究后， 中风认知障碍，中风最常见的长期后果。事实上， 中风幸存者经历持续的认知缺陷，多达四分之一的人随后被诊断为 痴呆这就迫切需要了解影响中风对健康的影响的个体因素。 大脑结构和功能，因为这为优化功能恢复提供了最好的希望。整体 这个团队科学项目的目的是了解一个人的性别如何塑造他们的神经免疫系统。 中风的反应，进而改变神经网络，以及认知和功能恢复。有三 重叠，但独立的项目，汇聚成为一个高度集成和有影响力的研究 项目这些实验旨在解决三个基本的，但还没有得到充分研究的问题 脑卒中后认知功能恢复的性别差异：（1）性腺因素的相对贡献 与染色体互补在认知恢复中的作用，（2）认知功能的性别差异是否 与中性粒细胞活性有关，以及（3）在神经元网络重映射中是否存在性别差异， 中风这些目标中的每一个都有其他两个目标的要素， 项目负责人;这种设计有效地编织了不同的专业知识，技术方法和科学 每个项目都有不同的视角，创造协同效应，并能够整合多个层面的成果 的分析。拟议的研究将构成随后的合作赠款申请的基础 重点是建立这些因素之间的因果关系，并确定它们的影响如何变化 影响中风后认知结果的因素。该项目还将在以下方面产生影响： 促进三名早期职业研究者寻求独立的中风基金，并通过扩大 WVU Stroke CoBRE啮齿动物行为核心的能力，以执行尖端的神经成像， 行为动物

PROJECT SUMMARY. The Overall Objective of the WVU Stroke CoBRE is to decrease morbidity and mortality related to stroke through improved understanding of pathophysiological mechanism(s) of stroke. We will accomplish this overall goal by conducting high-quality basic and translational research addressing the modifiable risk factors, biomarkers, mechanism(s), preventative strategies, acute and chronic treatments and rehabilitation of stroke. This objective would be met by achieving the following three Specific Aims: Specific Aim 1. Expand the critical mass of funded investigators conducting stroke recovery research. In Phase II we propose to solidify the commitment of investigators to stroke research, in part, by providing cutting-edge stroke research core facilities and services, generating meaningful preliminary data in support of their grant applications through funding of five early career investigator projects per year, providing grantsmanship workshops/activities to improve their grant applications, and expanding the intensive mentoring program initiated in Phase I of the WVU Stroke CoBRE. Specific Aim 2. Strengthen innovative scientific cores that support and advance basic and translational stroke research. We propose to expand the scope and capacity, as well as the user-base of these vital cores. This will be accomplished by the introduction of new services (e.g., new stroke models; additional behavioral tests), and provide training sessions for research cores. In addition to the Experimental Stroke Core (ESC) and the Rodent Behavior Core (RBC), which are proposed for CoBRE funding, we will develop two additional cores, the Mitochondrial Functional Assessment Core (MFAC) and the Stroke Tissue Bank. Specific Aim 3. Advance the ongoing development of an independent, sustainable, multidisciplinary thematic program of research on stroke. The goal of achieving independence of the WVU Stroke CoBRE has begun and will continue in Phase II by the transition to a user-fee based funding of research core services, the independent funding of research grants that include funding for these core services and support from the WVU Health Sciences College. At the conclusion of Phase II of the WVU Stroke CoBRE, mentored training will have been provided to engage additional early career investigators in stroke-related research. We will have addressed the need for basic and translational research into the causes, acute and subacute treatments and recovery from stroke by (1) increasing the number of independently funded WVU stroke researchers, (2) expanding stroke research core services and user numbers, and (3) continuing the transition to sustain these resources through a user-based funding model for services at WVU. The proposed WVU Stroke CoBRE Research Supplement aligns with all three of the WVU Stroke CoBRE aims and is expected to increase the parent award’s impact by fostering leading-edge research into post- stroke cognitive impairment, the most common long-term consequence of stroke. Indeed, more than half of stroke survivors experience persistent cognitive deficits and up to a quarter are subsequently diagnosed with dementia. This has created urgency to understand the individual factors that shape the impact of stroke on brain structure and function, as this offers the best hope for optimizing functional recovery. The Overall Objective of this Team Science Project is to understand how an individual’s sex shapes their neuroimmune response to stroke, in turn altering neuronal networks, and cognitive and functional recovery. There are three overlapping, but independent, projects that converge to become a highly integrated and impactful research project. The experiments are designed to address three fundamental, yet vastly understudied, questions related to sex differences in cognitive recovery after stroke: (1) the relative contributions of gonadal factors versus chromosomal complement in cognitive recovery, (2) whether sex differences in cognitive function are related to neutrophil activity, and (3) whether there are sex differences in neuronal network remapping after stroke. Each of these aims has elements of the other two aims introduced through collaboration among the Project Leaders; this design effectively weaves diverse expertise, technical approaches, and scientific perspectives into each project, creating synergy and the ability to integrate outcomes across multiple levels of analysis. The proposed research will form the foundation of a subsequent collaborative grant application focused on establishing causal relationships among these factors and determining how their influence varies across the lifespan in shaping cognitive outcomes after stroke. The project also will be impactful in terms of facilitating the pursuit of independent stroke funding by three early career investigators and through expansion of the capacity of the WVU Stroke CoBRE Rodent Behavior Core to perform cutting-edge neural imaging in behaving animals.