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Cerebral Autoregulation, Metabolic derangement, and Edema in Encephalopathy Outcome (CAMEEO)

脑病结果中的大脑自动调节、代谢紊乱和水肿 (CAMEEO)

基本信息

批准号：
10591879
负责人：
Eric Michael Liotta
金额：
$ 19.03万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-01 至 2028-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10591879
关键词：
Acceleration Acute Aging Alzheimer&apos s Disease Amino Acids Animal Model Area Aromatic Amino Acids Astrocytes Biological Markers Blood Vessels Blood brain barrier dysfunction Brain Brain Injuries COVID-19 Cell model Cephalic Cerebral Edema Cerebrovascular Circulation Cerebrovascular Disorders Cerebrum Cessation of life Chronic Clinical Cognition Cognitive Coma Complex Complication Confusion Critical Illness Data Delirium Dementia Development Doctor of Philosophy Edema Elements Encephalopathies Ensure Evaluation Foundations Functional disorder Glasgow Coma Scale Glial Fibrillary Acidic Protein Glutamates Goals Hepatic Encephalopathy Homeostasis Hospitalization Hospitals Hyperammonemia Hypotension Hypoxia Impaired cognition Impairment Intervention Invaded Knowledge Lead Link Liquid substance Magnetic Resonance Imaging Mass Spectrum Analysis Measures Mediating Medical Mentored Patient-Oriented Research Career Development Award Mentors Metabolic Metabolism Methodology Modeling Morbidity - disease rate Neurological outcome Neurologist Neurology Osmolalities Osmolar Concentration Outcome Outcome Assessment Pathologic Pathway interactions Patient-Focused Outcomes Patients Physicians Physiological Physiological Processes Quality of life Research Research Methodology Research Personnel Research Proposals Risk Risk Marker Risk Reduction Scanning Scientist Serum Severities Study models Survivors Syndrome Technical Expertise Techniques Time Training United States National Institutes of Health Universities Vascular Cognitive Impairment Vascular Dementia Viral Work X-Ray Computed Tomography acute stroke arm blood-brain barrier permeabilization brain volume career career development cell injury cerebrovascular cohort early onset follow-up functional decline functional disability functional outcomes gain of function human disease imaging biomarker improved insight mental state metabolomics mid-career faculty mind body interaction mortality risk neurophysiology patient oriented research pressure programs prospective prototype research study response skills translational approach

项目摘要

Project Summary/Abstract This K23 award application is for Eric Liotta, MD, a neurointensivist and Associate Professor of Neurology at Northwestern University. Dr. Liotta’s long-term goal is to become an independent physician scientist with expertise in the interactions between the brain and the body, in order to improve neurologic outcomes and reduce the risk of subsequent dementia following acute medical illness. To accomplish this goal, he will pursue a patient-oriented research agenda focused on delirium and encephalopathy with hepatic encephalopathy (HE) and COVID-19 associated encephalopathy (CAE) models. His mentored research program leverages career development activities through applications to the proposed research, culminating in his transition to research independence. He will develop broadly applicable expertise in systemic metabolic analysis, neurophysiologic evaluation, cognitive impairment and quality of life outcomes assessment, and patient-oriented research methods. He has assembled a team of mentors who will guide him in the transition to independent researcher. Farzaneh Sorond, MD PhD (mentor) is a neurointensivist who studies cerebral autoregulation, aging, and vascular cognitive impairment; Shyam Prabhakaran, MD MS (co-mentor) is a vascular neurologist who studies acute cerebrovascular disease with a focus on imaging-based markers of risk; and W. Taylor Kimberly, MD PhD (co-mentor) is a neurointensivist who studies cerebral and systemic metabolism in acute stroke. Acute encephalopathy (frequently called delirium) is pervasive in hospitalized patients. Encephalopathy survivors are at increased risk for cognitive impairment, vascular dementia, and Alzheimer’s dementia, though the mechanisms are unknown. Treating encephalopathy is hampered by incomplete knowledge of the relevant systemic derangements and the brain’s physiologic response to those derangements and their clinicopathologic syndromes. Dr. Liotta will investigate the hypothesis that osmolality and amino acid metabolic derangements result in cellular brain injury, cerebral edema, and impaired cerebral autoregulation that manifest acutely as encephalopathy, and chronically as cognitive impairments and elevated risk of early dementia development. Aim 1 will investigate the mechanism between metabolic derangements and cellular injury, cerebral edema, and cerebral autoregulation. Aim 2 will investigate the mechanism between cellular injury, cerebral edema, and cerebral autoregulation and clinical encephalopathy (delirium) severity. Aim 3 will investigate the mechanism between encephalopathy (delirium) burden and subsequent cognitive impairment. The study will use (1) repeated assessments of metabolic and physiologic derangements to elucidate the relationship with encephalopathy severity and (2) longitudinal follow up to investigate the relationship to cognitive impairment. By completing these aims, Dr. Liotta will gain a substantive foundation in brain-body interactions during acute illness that can be utilized to elucidate mechanistic targets to reduce cognitive impairment and risk of vascular dementia and Alzheimer’s dementia following encephalopathy and acute medical illness.

项目总结/摘要这个K23奖的申请是埃里克Liotta，医学博士，神经重症和神经病学副教授在西北大学。Liotta博士的长期目标是成为一名独立的医生科学家，在大脑和身体之间的相互作用的专业知识，以改善神经功能的结果，降低急性内科疾病后继发痴呆症的风险。为了实现这一目标，他将以患者为导向的研究议程，重点关注谵妄和肝性脑病（HE）和COVID-19相关脑病（CAE）模型。他的导师研究计划利用职业生涯发展活动，通过应用到拟议的研究，最终在他过渡到研究独立他将在系统代谢分析、神经生理学和神经生理学方面发展广泛适用的专业知识。评估、认知障碍和生活质量结果评估以及以患者为导向的研究方法.他已经组建了一个导师团队，他们将指导他向独立研究人员过渡。 Farzaneh Sorond，MD PhD（导师）是一名神经强化医师，研究大脑自动调节，衰老和血管性认知障碍; Shyam Prabhakaran，MD MS（共同导师）是一名血管神经学家，研究急性脑血管疾病，重点是基于成像的风险标志物; W. Taylor Kimberly，医学博士（共同导师）是一名神经重症监护医师，研究急性中风的大脑和全身代谢。急性脑病（常称为谵妄）在住院患者中普遍存在。脑病但是，幸存者患认知障碍、血管性痴呆和阿尔茨海默氏痴呆的风险增加，其机制尚不清楚。治疗脑病是阻碍了不完全的知识，相关的系统紊乱和大脑对这些紊乱的生理反应及其临床病理学综合征Liotta博士将研究渗透压摩尔浓度和氨基酸代谢紊乱导致细胞脑损伤、脑水肿和脑自动调节受损，急性表现为脑病，并长期作为认知障碍和早期痴呆发展的风险增加。目的1探讨代谢紊乱与细胞损伤、脑水肿、和大脑自动调节目的2探讨细胞损伤、脑水肿和脑缺血再灌注损伤之间的机制，脑自动调节和临床脑病（谵妄）的严重程度。目标3将研究其机制脑病（谵妄）负担和随后的认知障碍之间的关系。本研究将使用（1）反复评估代谢和生理紊乱，以阐明与脑病严重程度和（2）纵向随访，以研究与认知功能障碍的关系。通过完成这些目标后，利奥塔博士将在急性脑-体相互作用方面获得实质性基础。可用于阐明机制靶点以降低认知障碍和血管疾病风险的疾病痴呆症和阿尔茨海默氏痴呆症后脑病和急性医学疾病。