Traumatic Brain Injury- Understanding Disease Mechanisms by In vitro tools

Traumatic brain injury (TBI) affects 1.7 million people annually in the United States and is now commonly acknowledged as a risk factor for neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis. Yet there is a lack of understanding of the disease mechanisms underlying TBI and no effective therapeutic strategies. To date, there are no U.S. Food and Drug Administration (FDA)-approved biomarkers for the diagnosis or prognosis of TBI, and the molecular mechanisms of TBI response remain poorly understood. This lack of understanding reflects the complex, multifactorial nature of cellular responses to TBI and the need for better models for TBI study. By using our novel in vitro system for studying TBI we studied what is the cell response to mechanical injury, this includes proteomics, electrophysiology and metabolic changes. Our data enabled us to identify the main pathways affected by TBI, the time frame by which these changes occur and to identify 8 potential drugs to treat TBI. Furthermore, due to the importance of new more “in vivo like” TBI models, we developed a unique in vitro tri-synaptic pathway which incorporates 3 different brain regions and enabled us to identify how TBI affect each brain region (prefrontal cortex, amygdala, hippocampus) independently and collectively. Interestingly we found that in vitro cells, originated from different brain regions show significant differences before and after TBI and stress out the significant for implementation of cells from different brain regions in in vitro models.  This work demonstrates how new tools for brain research contributes to more understanding of the mechanisms underline TBI and gives new avenues to identify and test therapeutics.