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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.