Combining In Vitro Experiments and Computer Modeling to Study Mitochondrial Dysfunction After Brain Injury

Head injuries are common in motor vehicle collisions, construction site accidents, contact sports, and combat. While the physics of head impacts and pressure waves have been quantified, little is understood about how these types of impacts affect cells within the brain. Recent experiments indicate mitochondrial dysfunction is an important aspect of the process. This award will support research focused on gaining critical insights into the biomechanics that link head impacts and the subsequent changes to mitochondria structure and function. Data from this research project will help to better determine the mechanisms that lead to concussion symptoms and, eventually, develop targeted treatments for head trauma. An increased understanding of this neurodegenerative pathway will advance the health and welfare of the American public because the overall burden of traumatic brain injury on the U.S. workforce is substantial, with an estimated $4 billion per year in acute costs and over $40 billion in related health care per year. The goal of this project is to build an integrated experimental-computational model that relates tissue level biomechanics to mitochondrial-cytoskeletal interactions. This will improve our understanding of injury to the central nervous system. The first objective is to calibrate and validate a continuum mixture theory-based model of the three-dimensional in vitro experiments. Subsequently, the research team will determine the mechanical inputs that cause mitochondrial and cellular dysfunction in neurons, astrocytes, and microglia. Together, these data will simultaneously expand our knowledge of fundamental neurodegenerative processes and multi-scale systems that exhibit coupled mechano-transport phenomena. The broader impacts of the work include building an experimental and analytical foundation for future biomechanical and mechanobiological discoveries, especially in conjunction with Artificial Intelligence-based analyses. By better understanding the role that mitochondria play in the pathology of traumatic brain injury, research teams will be better positioned to establish a foundation for understanding the progression of neurodegeneration in a variety of disease states. In addition, the project will produce new extracurricular teaching modules, termed MILESTONES that will teach students how to design biocompatible tools for exploring cell biology. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2607975 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Eric Nauman | Institution: University of Cincinnati Main Campus, CINCINNATI, OH | Award Amount: $590,513 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2607975 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2607975.html