The potential for animal models to provide insight into mild traumatic brain injury: Translational challenges and strategies

- Mild traumatic brain injuries (mTBI) are common and in need of scientific research.
- There are confounding variables and limitations in mTBI patient studies.
- The use of animal models of may complement mTBI patient studies.
- Strengths/limitations of each model should be considered in study design and interpretation.
- Combined patient and animal model approach may allow for evidence-based translation to clinical management.

Mild traumatic brain injury (mTBI) is a common health problem. There is tremendous variability and heterogeneity in human mTBI, including mechanisms of injury, biomechanical forces, injury severity, spatial and temporal pathophysiology, genetic factors, pre-injury vulnerability and resilience factors, and clinical outcomes. Animal models greatly reduce this variability and heterogeneity, and provide a means to study mTBI in a rigorous, controlled, and efficient manner. Rodent models, in particular, are time- and cost-efficient, and they allow researchers to measure morphological, cellular, molecular, and behavioral variables in a single study. However, inter-species differences in anatomy, morphology, metabolism, neurobiology, and lifespan create translational challenges. Although the term “mild” TBI is used often in the pre-clinical literature, clearly defined criteria for mild, moderate, and severe TBI in animal models have not been agreed upon. In this review, we introduce current issues facing the mTBI field, summarize the available research methodologies and previous studies in mTBI animal models, and discuss how a translational research approach may be useful in advancing our understanding and management of mTBI.