The pros and cons of motor, memory, and emotion-related behavioral tests in the mouse traumatic brain injury model

Traumatic brain injury (TBI) is a medical emergency with high morbidity and mortality. Motor, memory, and emotion-related deficits are common symptoms following TBI, yet treatment is very limited. To develop new drugs and find new therapeutic avenues, a wide variety of TBI models have been established to mimic the heterogeneity of TBI. In this regard, along with histologic measures, behavioral functional outcomes provide valuable insight into the underlying neuropathology and guide neurorehabilitation efforts for neuropsychiatric impairment after TBI. Development, characterization, and application of behavioral tests that can assess functional neurologic deficits are essential to the development of translational therapies. This comprehensive review aims to summarize 19 common behavioral tests from three aspects (motor, memory, and emotion-related) that are associated with TBI pathology. Discussion covers the apparatus, the test steps, the evaluation indexes, data collection and analysis, animal performance and applications, advantages and disadvantages as well as precautions to eliminate bias wherever possible. We discussed recent studies on TBI-related preconditioning, biomarkers, and optimized behavioral protocols. The neuropsychologic tests employed in clinics were correlated with those used in mouse TBI models. In summary, this review provides a comprehensive, up-to-date reference for TBI researchers to choose the right neurobehavioral protocol according to the research objectives of their translational investigation.