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

Project: Research project

Project Details

Description

This K23 award application is for Eric Liotta, MD, a neurointensivist and Assistant 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 after acute medical illness. To accomplish this goal, he will pursue a patient-oriented research agenda focused on encephalopathy (generalized brain dysfunction) with hepatic encephalopathy (HE) and COVID-19 associated encephalopathy (CAE) disease models. His mentored research program leverages career development activities through applications to the proposed research, culminating in his transition to research career independence. He will develop broadly applicable skills and expertise in systemic metabolic analysis, neurophysiologic evaluation, cognitive 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 and brain injury mechanisms; 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.Encephalopathy is pervasive in hospitalized patients, and encephalopathy survivors are at increased risk for chronic cognitive impairment, though the causative mechanisms are unknown. Advances in treating encephalopathy are 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 astrocyte (brain cell) injury, cerebral edema, and impaired cerebral autoregulation that manifest acutely as encephalopathy, and chronically as cognitive and quality of life impairments. Aim 1 will investigate the mechanism between metabolic derangements and astrocyte injury, cerebral edema, and cerebral autoregulation. Aim 2 will investigate the mechanism between astrocyte injury, cerebral edema, and cerebral autoregulation and acute clinical encephalopathy severity. Aim 3 will investigate the mechanism between acute encephalopathy burden and subsequent cognitive and quality of life outcomes. 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 and quality of life outcomes. By completing these aims, Dr. Liotta will gain a substantive foundation in the interactions between the brain and the body’s organ systems that can be leveraged to elucidate mechanistic targets for therapeutic development. Dr. Liotta is well-positioned to perform this research, given his clinical expertise, prior research experiences, and network of mentors.
StatusActive
Effective start/end date2/1/231/31/28

Funding

  • National Institute on Aging (5K23AG078705-02)

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