Presentation Title: TBI-on-a-chip: Linking physical impact to neurodegeneration by deciphering primary and secondary injury mechanisms
Author Name(s): Edmond A. Rogers1,2,3, Timothy Beauclair1,2, Guenter W. Gross3, and Riyi Shi1,2
Author Department and School Affiliation: 1Department of Basic Medical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907; 2Weldon School of Biomedical Engineering Purdue University, West Lafayette, IN 47907; 3Department of Biological Sciences and Center for Network Neuroscience University of North Texas, Denton TX 76203
Abstract: We have engineered a highly-novel, primary culture-model to reproduce clinically-relevant g-forces with unprecedented temporal and spatial resolution for mechanistic investigations into post-TBI (traumatic brain injury) neurodegeneration.
Using neuronal networks grown on multielectrode-arrays with a pendulum-injury device and standard immunofluorescent methods, we noted significant, force-dependent increases in the ROS acrolein at 24hrs post-impact, indicative of post-impact neuronal degeneration. These changes were amplified by the following: exposure to higher g-forces (30-250g, peak); the rapid (4-6sec interval) application of multiple impacts (1,3,5 and 10x); and exposure to 40mM EtOH for a 10min duration immediately following impact. Further, we demonstrate the enhancement of injury-recovery as a function of increasing time intervals between repeated hits. In addition, conditioned media from maximally-impacted cultures can cause acrolein elevation when introduced to non-impact, control networks, indicating acrolein’s role as a diffusive-factor in post-TBI secondary injuries.
This model recreates trauma with sub-cellular resolution and has the ability to separate primary and secondary injuries. With this newly established in vitro tool, combined with our available in vivo models, we expect to gain insight into the mechanisms underpinning TBI (acute and chronic) and its link to neurodegeneration, helping to guide our translational laboratory endeavors and improving clinical diagnoses and treatments.