A bilateral head injury that shows graded brain damage and behavioral deficits in adultmice

Reliable animal models of traumatic brain injury (TBI) are essential to test novel hypotheses and therapeutic interventions. In this study, based on advantages of both the closed head injury (CHI) and controlled cortical impact (CCI) models, we developed a bilateral head injury model in mice. C57BL/6 mice were used in this study. A midline craniotomy (5mm diameter) was performed extending 2mm anteriorly and 3mm posteriorly from the bregma, centered over the sagittal suture. The skull flap was left in place. A cortical impact on the surface of the skull flap was performed using an electromagnetic impactor. Here we report that the injury significantly decreased the neuroscore and increased foot drops in a severity-dependent manner. Severity-related deficits in performance on a rotarod device were also found at both slow and fast accelerations. These findings suggest that our TBI model can produce graded motor deficits. In addition, Morris water maze testing showed increased latency to locate a hidden platform in a severity-dependent manner, suggesting that our model can also produce graded memory deficits. Furthermore, an adhesive removal test revealed significant increases in time-to-contact and time-to-remove the adhesive tape from the paw in a severity-dependent manner, indicating that our TBI model produced graded somatosensory and motor deficits. Histological analysis presented a clear gradation in brain tissue damage following graded brain injuries. These findings collectively suggest that the current model may offer a sensitive, reliable and clinically-relevant model for assessments of therapeutic strategies forTBI.