Neuronal Signaling Signatures of Neuroinflammatory Pathways Following Traumatic Brain Injury
Abstract
Approved for Public ReleaseABSTRACTThe emergence of neuroinflammatory pathways in the brain is linked to traumatic brain injury (TBI,) and a slew of other neurodegenerative conditions. Successful therapeutic interventions are lacking, primarily due to the absence o,f precise diagnostic biomarkers to identify dysfunctional cell signaling pathways associated with mechanical injury. This precludes,the design of proper neurobiological assays for basic research and screening of potential clinical pharmacological agents to mitigat,e neurodegenerative processes that impair brain function. In this project, we intend to develop and utilize an in vitro TBI stretch-,based model to apply reproducible mechanical injury at single-cell precision to identify alterations in cellular signaling and expre,ssion of neuroinflammatory markers. Applying controlled strain to neuronal networks in heterogeneous cortical cultures in parallel w,ith real-time high-speed calcium and voltage imaging will allow for robust biomechanical and electrophysiological characterization a,t both the circuit-level and single-neuron level during morphological deformation post injury. This will allow application of mechan,ical strain with the level of accuracy required to assume a correlation between strain and injury response, neural activity and infl,ammatory pathways. The project poses a unique opportunity to correlate brain activity signatures with microglia activation to deciph,er neuroinflammation and augment diagnostic capabilities.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 04, 2022
- Source ID
- N000142312006
Entities
People
- Aviad Hai
Organizations
- Office of Naval Research
- United States Navy
- University of Wisconsin System