Defining Experimental Variability in Actuator-Driven Closed Head Impact in Rats

Traumatic brain injury (TBI) is a world-wide health challenge that lacks tools for diagnosis and treatment. There is a need for translational preclinical models to effectively design clinical tools, however, the diversity of models is a barrier to reproducible studies. Actuator-driven closed head impact (AD-CHI) models have translational advantages in replicating the pathophysiological and behavioral outcomes resulting from impact TBI. The main advantages of AD-CHI protocols include versatility of impact parameters such as impact angle, velocity, depth, and dwell time with the ability to interchange tip types, leading to consistent outcomes without the need for craniectomy. Sources of experimental variability within AD-CHI rat models are identified within this review with the aim of supporting further characterization to improve translational value. Primary areas of variability may be attributed to lack of standardization of head stabilization methods, reporting of tip properties, and performance of acute neurological assessments. AD-CHI models were also found to be more prevalently used among pediatric and repeated TBI paradigms. As this model continues to grow in use, establishing the relationships between impact parameters and associated injury outcomes will reduce experimental variability between research groups and encourage meaningful discussions as the community moves towards common data elements.