This Project Grant award, provided by the National Institute on Aging under the Aging Research program (CFDA 93.866), will support the development of novel gyrencephalic animal models to study the neuropathological and clinical features of post-traumatic brain injury (TBI) neurodegeneration. The award, totaling $3,102,638, will fund research to create preclinical TBI models that recapitulate the complex pathologies and phenotypes observed in the chronic phase following injury. Key activities...
This $559,820 Project Grant awarded by the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) will fund research to improve the understanding and prediction of traumatic brain injury (TBI) biomechanics. The grant supports a collaborative effort between researchers at the University of South Carolina and The Henry M. Jackson Foundation for the Advancement of Military Medicine to:...
The National Institute of Biomedical Imaging and Bioengineering (NIBIB) awarded a $389,813 Project Grant (R21EB034428) to the University of California, Los Angeles (UCLA) to develop and assess novel frameworks that can be employed in early post-traumatic brain injury (TBI) care. The project aims to leverage non-parametric models and machine learning techniques to fuse and incorporate routine multimodal and multiplex magnetic resonance imaging (MRI) signals into a prediction framework. This is...
The Project Grant award F31NS139434, funded by the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, is supporting research to investigate the link between traumatic brain injury (TBI), hematopoietic stem cell dysfunction, chronic neurodegeneration, and Alzheimer's disease (AD). The $102,948 award, with a performance period from Dec 1, 2024 to Aug 31, 2027, is being...
This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) federal grant program, will fund research to investigate the mechanisms of chronic blood-brain barrier (BBB) dysfunction after traumatic brain injury (TBI). The $404,100 award to The General Hospital Corporation, doing business as Massachusetts General Hospital (MGH), aims to identify an endothelial...
The University of Georgia Research Foundation, Inc. (UGA Research Foundation) was awarded a $379,171 Project Grant from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program. The grant supports a 2-year research project to investigate cerebrovascular dysfunction and cerebral atrophy in severe traumatic brain injury (STBI). Specifically, the project aims to: 1) Characterize...
This Project Grant award from the National Science Foundation (NSF) Engineering program (CFDA 47.041) will support research to study how astrocytes, a critical cell type in the brain, respond to mechanical forces and strain associated with traumatic brain injury (TBI). The $705,806 award to Tufts University will fund the development of controlled 3D brain-like cell culture environments and ex vivo brain cultures to quantify astrocytes' acute and chronic responses to mechanical perturbation...
This federal Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, provides $465,752 to the University of Michigan-Dearborn to conduct research on understanding the relationship between cell chirality and cell-cell interactions within the neurovascular unit (NVU) after traumatic brain injury (TBI). The research aims to evaluate TBI-induced...
This $274,855 Project Grant award from the National Science Foundation (NSF) under the NSF Technology, Innovation, and Partnerships (CFDA 47.084) program supports the development of a novel fusion protein construct (NFP) that can cross the blood-brain barrier and deliver a therapeutic payload to repair mitochondrial DNA damage in neurons following traumatic brain injury (TBI). The key objectives of this 8-month research and development effort are to: 1) verify the NFP's technical capability to...
This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) federal grant program, will fund research at the Augusta University Research Institute, Inc. (doing business as Georgia Health Sciences) to investigate the mechanisms linking traumatic brain injury (TBI) to subsequent neurodegeneration and dementia. The $1,975,262 award will support a 3-year study...
LASTING IMPACTS: DYNAMIC, FULLY NATURAL BIOPRINTED 3D HUMAN NEUROVASCULAR BIOMIMETIC MODEL TO STUDY TRAUMATIC BRAIN INJURY PATHOPHYSIOLOGY - ABSTRACT LASTING IMPACTS: DYNAMIC, FULLY NATURAL BIOPRINTED 3D HUMAN NEUROVASCULAR BIOMIMETIC TO STUDY TRAUMATIC BRAIN INJURY PATHOPHYSIOLOGY EVERY YEAR AN ESTIMATED 2.5 MILLION PEOPLE SUSTAIN A TRAUMATIC BRAIN INJURY (TBI), AND MANY SURVIVORS EXPERIENCE SUBSEQUENT LONG-TERM COGNITIVE DEFICITS, SENSORIMOTOR IMPAIRMENTS, AND NEUROPSYCHIATRIC DISABILITY THAT RESULT IN PROFOUND PSYCHOSOCIAL AND ECONOMIC CONSEQUENCES FOR AFFECTED INDIVIDUALS. ACUTE AND CHRONIC EFFECTS OF NEUROTRAUMA REPRESENT LEADING CAUSES OF MORTALITY, MORBIDITY, AND LONG-TERM DISABILITY IN THE US AND AROUND THE WORLD. ALTHOUGH TBI IS CLEARLY DEFINED NEUROPATHOLOGICALLY, LESS WELL-DEFINED IS THE RELATIONSHIP BETWEEN THE INITIAL IMPACT AND THE RESULTING PROGRESSION OF TRAUMA-RELATED NEUROVASCULAR PATHOLOGY. THIS MULTIDISCIPLINARY MULTI-PI PROPOSAL IS RESPONSIVE TO THE TRANS-AGENCY BLOOD-BRAIN INTERFACE PROGRAM (RFA-HL-20-021, R61/R33) AND BUILDS ON A LONGSTANDING COLLABORATION BETWEEN LAWRENCE LIVERMORE NATIONAL LABORATORY, BOSTON UNIVERSITY SCHOOL OF MEDICINE, AND THE NIH/NIA-FUNDED BOSTON UNIVERSITY ALZHEIMER'S DISEASE CENTER TO ADDRESS FUNDAMENTAL MECHANISMS UNDERPINNING ACUTE AND CHRONIC EFFECTS OF NEUROTRAUMA, INCLUDING TRAUMA-INDUCED MICROVASCULAR INJURY AND LATENT TAU PROTEIN NEURODEGENERATIVE PATHOLOGIES ASSOCIATED WITH CHRONIC TRAUMATIC ENCEPHALOPATHY (CTE). THIS PROJECT WILL DEVELOP AND CHARACTERIZE A HUMAN IN VITRO PERFUSABLE NEUROVASCULAR UNIT (NVU) MODEL WITH THE OVERARCHING GOAL OF IDENTIFYING BIOMECHANICAL TRIGGERS AND MOLECULAR-CELLULAR RESPONSES TO BRAIN INJURY THAT DETERMINE THE LOCATION, SEVERITY, AND PROGRESSION OF TRAUMATIC MICROVASCULAR INJURY (TMI), BLOOD- BRAIN BARRIER (BBB) DISRUPTION, AND PHOSPHORYLATED TAU PROTEINOPATHY. TO ACCOMPLISH THIS OBJECTIVE, THIS WORK WILL LEVERAGE AN EXISTING BBB PLATFORM TO BIOFABRICATE A 3D MULTI-CELLULAR DYNAMIC HUMAN NVU BIOMIMETIC WITH PERFUSABLE ENDOTHELIALIZED VASCULATURE. THE RESULTING OPTICALLY CLEAR NVU PLATFORM WILL ENABLE SYSTEMATIC INTERROGATION OF THE HUMAN CEREBROVASCULATURE, INCLUDING ALL HUMAN NVU CELL TYPES, WITH SPATIOTEMPORAL CONTROL AND STRUCTURE-FUNCTION MEASUREMENTS IN REAL-TIME. IN THE R61 PHASE, WE WILL MODIFY OUR EXISTING 3D-PRINTED BBB MODEL TO INCLUDE CULTURE OF HUMAN INDUCED PLURIPOTENT STEM CELL (IPSC)-DERIVED ENDOTHELIA, PERICYTES, ASTROCYTES, AND NEURONS. EFFECTS OF CELLULAR COMPOSITION, STRUCTURE-FUNCTION RELATIONS, FLUID FLOW DYNAMICS (INTRAVASCULAR, INTERSTITIAL), AND CULTURE INCUBATION CONDITIONS ON IPSC MATURATION WILL BE INVESTIGATED. IN THE R61 PHASE, WE WILL DEVELOP A PLATFORM-COMPATIBLE INJURY INSTRUMENT INFORMED BY COMPUTATIONAL SIMULATIONS TO MATCH LOADS USED IN IN VIVO ANIMAL STUDIES. EMBEDDED MARKERS IN THE 3D-PRINTED MODEL WILL ENABLE DIRECT MEASUREMENT AND VISUALIZATION OF TIME-VARYING STRAIN DURING IMPACT AS A FUNCTION OF VASCULAR, GLIAL, AND NEURONAL PATHOLOGY AND COMPROMISED FUNCTION (R33 PHASE). IN ADDITION, WE WILL INVESTIGATE MOLECULAR, CELLULAR, AND FUNCTIONAL EFFECTS OF SECONDARY DAMAGE POST-TBI INJURY. RESULTS WILL BE INFORMED BY COMPANION STUDIES IN EXPERIMENTAL ANIMALS AND CLINICOPATHOLOGICAL CORRELATION WITH UNIQUE HUMAN BRAIN SPECIMENS. THIS PROJECT WILL CONTRIBUTE TO FUNDAMENTAL UNDERSTANDING OF BRAIN INJURY BIOMECHANICS AND RELATIONSHIP TO ACUTE AND CHRONIC EFFECTS OF NEUROTRAUMA IN THE HUMAN BRAIN.