MOUSE STRAIN SHAPES BEHAVIORAL VULNERABILITY TO MILD TRAUMATIC BRAIN INJURY

Background: A major challenge in preclinical mild traumatic brain injury (mTBI) research is the variability in reported behavioral outcomes across studies, even when similar injury paradigms are applied. This inconsistency complicates reproducibility, limits cross-study comparability, and hampers the translation of successful intervention studies to the clinical setting. Differences in experimental standards, outcome measures, and genetic background are increasingly recognized as key contributors, yet their relative impact remains insufficiently defined.
Methods: Adult male C57BL/6 (inbred) and ICR (outbred) mice were subjected to closed-head mTBI or sham procedures. Behavioral assessment was conducted seven days post-injury using a combination of widely used standardized behavioral tests alongside novel continuous home-cage monitoring. This integrative approach enabled both broad functional screening and sensitive detection of subtle, ethologically relevant behavioral motifs. Factorial statistical analyses were applied to examine main effects of strain and injury, as well as their interaction.
Results: Baseline behavioral profiles differed markedly between strains across multiple domains. Following mTBI, injury-related effects were not uniformly expressed across assays but emerged selectively in relation to strain and measurement sensitivity. Continuous home-cage–based measures revealed interesting results, shedding light on strain involvement in mTBI studies.
Conclusions: Together, these findings suggest that strain selection and behavioral assay sensitivity critically shape the detectability of mTBI-related phenotypes. By integrating standard paradigms with home-cage–based monitoring, this study provides a framework for improving reproducibility and refining translational interpretation in preclinical mTBI research.