A Novel Approach for the Development and Characterization of a Large Animal Model of Traumatic Brain Injury (TBI)

Blunt craniocerebral trauma is the leading cause of death and morbidity in young adults. Survivors of traumatic brain injury (TBI) exhibit serious acute and chronic deficits in physical and cognitive performance. To advance the study of TBI therapeutic strategies, realistic and reproducible animal models are essential in order to translate data from these studies to brain‐injured humans. In order to improve the standardization of high‐velocity trauma, the present study characterizes a novel large animal (sheep) model of closed TBI which will allow the study of both acute and long‐term chronic outcomes. The following steps were taken to develop and characterize a large animal sheep model of closed TBI: 1) a humane bolt stunner with an integrated oscillation absorber for prevention of skull fractures was characterized with respect to impact dynamics (see Figure); 2) a robotic assist device with elastic bands was developed to off‐set gravitational and rotational forces due to the stunner weight. Thus, the impact force can be reproducibly and precisely applied in all directions to the surface of the head; 3) the degree of closed head trauma severity was established using different charges; and 4) trauma analysis via physiologic, and biochemical outcomes were performed. The model presented herein achieves an advance in standardization of severe, closed TBI, as well as providing heterogeneity of brain pathophysiology that parallels clinical brain changes observed in patients after high‐energy trauma. As such, this model closes the gap between experimental closed TBI in large animal models and clinical studies.DOD/ONR;N000141210597;N000141210810.