Role of Endothelial and Brain Injury in Acute and Long-term Brain Dysfunction

内皮和脑损伤在急性和长期脑功能障碍中的作用

基本信息

批准号：
8755133
负责人：
Christopher Hughes
金额：
$ 11.78万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8755133
关键词：
Accounting Acute Affect Age Aging Alzheimer&apos s Disease American Area Biochemical Biological Markers Biology Blood Blood - brain barrier anatomy Blood Vessels Blood flow Blood specimen Brain Brain Injuries Brain-Derived Neurotrophic Factor Clinical Trials Cognition Cognitive Cognitive deficits Coma Confusion Critical Illness Data Delirium Dependence E-Selectin Elderly Endothelium Enrollment Exposure to Functional disorder Funding Future Grant Hospital Costs Hospitals Impaired cognition Impairment Incidence Injury Lead Length of Stay Literature Measures Mediator of activation protein Medical Metabolism Methods Morbidity - disease rate Neurologic Neuronal Injury Neurons Organ Outcome Pathway interactions Patients Permeability Physical therapy Physicians Plasma Plasminogen Activator Inhibitor 1 Population Prevention Prevention strategy Principal Investigator Property Public Health Publishing Research Research Personnel Research Project Grants Resources Risk Factors Role Scientist Stimulus Survivors Testing Therapy Clinical Trials Trail Making Test Traumatic Brain Injury UCHL1 gene United States National Institutes of Health Vasomotor Work aging brain base brain research career development cohort common treatment cost design endothelial dysfunction executive function experience follow-up high risk improved insight medical schools mortality multicatalytic endopeptidase complex neuropsychological older patient public health relevance retiree therapy design ubiquitin C-terminal hydrolase

项目摘要

DESCRIPTION (provided by applicant): Brain dysfunction is prevalent in the critically ill elderly, presenting in the acute setting as delirium or coma or in the long-term as impairment in global cognition and executive functioning. This brain dysfunction results in increased hospital cost, length of stay, functional dependence, and mortality. The pathophysiology of this brain dysfunction remains unclear but likely involves endothelial dysfunction and injury to the blood brain barrier and neurons. With the increasing age of the population and continued high morbidity from critical illness states, the acute and long-term cognitive effects of critical illnes that are unique to the elderly must be studied, and the mechanistic roles of potential pathophysiological pathways such as endothelial dysfunction and neurologic injury in this brain dysfunction of the elderly must be elucidated. The overall objectives of this research project, therefore, focus on testing the global hypothesis that systemic endothelial dysfunction and neurologic injury lead to acute brain dysfunction during critical illness and long-term cognitive impairment after in survivors. This research will provide new insights into the pathophysiology of critical illness brain dysfunction, and this grant will allow the principal investigator to delve ito these pathophysiological mechanisms while gaining experience in the unique challenges of researching brain dysfunction in the elderly. The data obtained during this grant period will lead toward more detailed mechanistic studies by the principal investigator of brain dysfunction in the elderly. Importantly, the results of this line of research may lead to future therapeutic trials of endothelial or blood brain barrier modulation designed to improve the cognitive outcomes our elderly ICU patients.

描述（由申请人提供）：脑功能障碍在重症老年中普遍存在，以del妄或昏迷或长期作为全球认知和执行功能的损害，以急性环境表示。这种大脑功能障碍导致医院成本增加，住院时间，功能依赖性和死亡率。该大脑功能障碍的病理生理尚不清楚，但可能涉及内皮功能障碍和血液脑屏障和神经元的损伤。随着人口年龄的增长并持续危重疾病状态的高发病率，必须研究老年人所独有的急性和长期认知作用，并且必须在这种老年人的大脑功能障碍中进行潜在的病理生理途径（例如内皮功能障碍和神经学损伤）的机械作用。因此，该研究项目的总体目标侧重于测试全球假设，即系统性内皮功能障碍和神经系统损伤导致急性疾病期间急性脑功能障碍和幸存者后的长期认知障碍。这项研究将为重症疾病脑功能障碍的病理生理提供新的见解，该赠款将使主要研究者能够深入研究这些病理生理机制，同时在研究老年人研究脑功能障碍的独特挑战中获得经验。在此赠款期间获得的数据将导致老年人脑功能障碍的主要研究者进行更详细的机械研究。重要的是，这一研究的结果可能会导致未来的治疗试验内皮或血脑屏障调节旨在改善我们的老年ICU患者的认知结果。