Exploration of the molecular basis of blast injury in a biofidelic model of traumatic brain injury
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Biological response to blast overpressure is complex and results in various and potentially non-concomitant acute and long-term deficits to exposed individuals. Clinical links between blast severity and injury outcomes remain elusive and have yet to be fully described, resulting in a critical inability to develop associated protection and mitigation strategies. Further, experimental models frequently fail to reproduce observed physiological phenomena and/or introduce artifacts that confound analysis and reproducibility. New models are required that employ consistent mechanical inputs, scale with biological analogs and known clinical data, and permit high-throughput examination of biological responses for a range of environmental and battlefield- relevant exposures. Here we describe a novel, biofidelic headform capable of integrating complex biological samples for blast exposure studies. We additionally demonstrate its utility in detecting acute transcriptional responses in the model organism Caenorhabditis elegans after exposure to blast overpressure. This approach enables correlation between mechanical exposure and biological outcome, permitting both the enhancement of existing surrogate and computational models and the high-throughput biofidelic testing of current and future protection systems.
KeywordsBlast injury Traumatic brain injury Biofidelic headform Caenorhabditis elegans Transcriptomics
We would like to thank Ian Wing and Ken Harclerode for their assistance in headform design, as well as Seneca Bessling, Nathan Boggs, Rozanne Mungai, Melissa Theodore, and Sherry Zhang for assistance during blast overpressure experiments. Figures were generated using MATLAB and Adobe Illustrator software. This work was enabled through the Johns Hopkins University Applied Physics Laboratory Independent Research and Development Program.
Author’s contributions Peter Thielen, Thomas Mehoke, Brock Wester, and Jessica Dymond designed and implemented experiments. Jeffery Paulson designed and executed the fabrication process for the headform. Thomas Mehoke performed data analysis for transcriptional profiling experiments, Julie Gleason and Alexander Iwaskiw analyzed data, and all authors contributed to the writing of the manuscript.
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