Gap-Based Milieu Biomarkers for Traumatic Brain Injury (GAMBIT-TBI)
Abstract
OVERALL PROGRAM: Gap-based Milieu Biomarkers for Traumatic Brain Injury (GAMBIT- TBI) Traumatic Brain Injury (TBI) and Psychological Health Research Program was initiated in 2007 in response to the traumatic brain injuries sustained and psychological health issues experienced by deployed forces in Iraq and Afghanistan. Department of Defense (DOD) efforts have continued toward promoting a better standard of care for psychological health and TBI in the areas of prevention, detection, diagnosis, treatment, and rehabilitation. Our research program, titled Gap-based Milieu Biomarkers for Traumatic Brain Injury (GAMBIT-TBI), addresses two Focus Areas and their associated sub-areas: I. Focus Area 2 (Prevent) - Sub-area 2a: We will address the progression of TBI through the analyses of archived patient biofluid samples and new patient recruitment. II. Focus Area 1 (Understand) - Sub-area 1a: Research on the progression of TBI will be strengthened and enhanced by identifying and addressing knowledge gaps in TBI etiology. We will identify and validate underdeveloped blood-derived central nervous system (CNS) and immune response domain biomarkers, neuroimaging and correlation with environmental, biological, and pathophysiological influences affecting cognition, emotional sequelae, and long-term outcomes. Background and Unmet Needs: Although there have been major advances in the field of TBI, there still remain important and essential unfilled and unanswered clinical knowledge gaps, especially regarding the heterogeneity of TBI pathology and subphenotypes. Some knowledge gaps that need to be addressed include: (i) improvements are needed in classification of injury to better understand injury complexity, severity and dose effects; (ii) advances in tools and technologies are necessary not only for improved quantification and qualification of injuries, but to also provide a better understanding about TBI-induced disturbances in cellular physiology and its link to CNS pathology and cognitive dysfunction; (iii) lack of objective diagnostic and prognostic biomarkers to predict long-term impact of TBI. This includes improved selection of biomarkers and minimally invasive detection modalities (biochemical, neuroimaging); (iv) lack of understanding of long-term outcomes following TBI; (v) insufficient neurocognitive assessments at the chronic phase for mild/moderate/severe phases; (vi) lack of diagnostic and prognostic markers (biochemical, neuroimaging) that predict long-term impact for mild TBI. Our proposal describes a multimodal strategy using biochemical and imaging biomarkers for early detection and/or monitoring over time of comorbidities, neurodegeneration, and genetic/epigenetic factors leading to chronic complications. Further, we will be using blood-based CNS biomarker assays to determine trajectories of long-term outcomes. Understanding the trajectories and pathobiology of acute and chronic recovery in terms of chronic conditions and neurodegeneration. We will be examining how CNS and non-CNS inflammatory pathways correlate with damage to brain cell types and changes in cognition and behavior. We will be investigating multi-modal use of existing and new biomarkers to enhance classification, monitor and support outcome measurement, and provide early detection of decline/comorbidities and neurodegeneration. To address these gaps, our proposal is divided into four major projects: Project 1: Acute and Post-Acute CNS Milieu Biomarkers to Aid in the Interrogation of TBI Subphenotypes and Cognitive/Emotional Deficits Project 2: Multi-Modal Biomarker Moderators of CNS Damage and Neurodegeneration After TBI Project 3: Multimodal Neuroimaging Assessment of Polytomous Mechanisms of Brain Health Decline After TBI Project 4: Plasma Cell-Free (cf) DNA Methylation Profiling for TBI Interrogation The overall focus of these four projects are summarized and include: (a) detection of existing and new blood-bas
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211089
Entities
People
- Richard Rubenstein
Organizations
- SUNY Downstate Health Sciences University
- United States Army