Diversity Supplement-Massoudi

项目摘要 血管性认知障碍和痴呆（VCID）是可归因于以下因素的任何水平的认知改变： 脑血管病VCID是仅次于阿尔茨海默病的痴呆症的第二大病因， 大约15-30%的痴呆病例。脑小血管疾病（cSVD）是一组影响脑血管疾病的病理学， 大脑的微循环，总共占所有中风的20%，是最常见的 VCID的病理学基础cSVD和VCID的影响预计将迅速增加， 美国和其他国家的年龄。重要的是，cSVD的发病机制尚未完全了解， 这是制定预防和治疗战略的一个主要障碍。本文中描述的研究 该提案将开发和验证五种新的cSVD小鼠模型，这些模型基于以下基因和突变： 被证明是导致人类疾病的原因。我们组建了一个跨学科的专家团队， 整合独特遗传资源、血管压力肌电描记术、膜片钳电生理学、钙 成像、专门的磁共振成像模式以及学习和记忆行为测定， 开发和表征cSVD的多种新型遗传模型，使用导致疾病的基因， 人类我们的长期目标是开发和采用遗传模型，忠实地概括重要的 人类cSVD和VCID的标志。

PROJECT SUMMARY Vascular cognitive impairment and dementia (VCID) is any level of cognitive alteration that is attributable to cerebrovascular pathologies. VCID is second only to Alzheimer’s disease as a cause of dementia and accounts for ~15-30% of all dementia cases. Cerebral small vessel diseases (cSVDs) are group of pathologies afflicting the microcirculation of the brain that collectively account for up to 20% of all strokes and is the most common pathology underlying VCID. The impact of cSVD and VCID is expected to increase rapidly as the population of the US and other countries ages. Importantly, the pathogeneses of cSVDs are incompletely understood which represents a major barrier in developing strategies for prevention and treatment. Research described in this proposal will develop and validate five novel mouse models of cSVD based on genes and mutations that are demonstrated to contribute to human disease. We have assembled an interdisciplinary team of experts that will integrate unique genetic resources, vascular pressure myography, patch-clamp electrophysiology, calcium imaging, specialized magnetic resonance imaging modalities and learning and memory behavior assays to develop and characterize multiple novel genetic models of cSVD using genes that contribute to disease in humans. Our long-term objective is to develop and employ genetic models that faithfully recapitulate important hallmarks of human cSVD and VCID.