A semicircular controlled cortical impact produces long-term motor and cognitive dysfunction that correlates well with damage to both the sensorimotor cortex and hippocampus

Abstract

Animal models of traumatic brain injury (TBI) are essential for testing novel hypotheses and therapeutic interventions. Unfortunately, due to the broad heterogeneity of TBI in humans, no single model has been able to reproduce the entire spectrum of these injuries. The controlled cortical impact (CCI) model is one of the most commonly used models of contusion TBI. However, behavioral evaluations have revealed transient impairment in motor function after CCI in rats and mice. Here we report a new semicircular CCI (S-CCI) model by increasing the impact tip area to cover both the motor cortex and hippocampal regions in adult mice. Mice were subjected to S-CCI or CCI using an electromagnetic impactor (Impactor OneTM, MyNeuroLab; semicircular tip: 3mm radius; CCI tip diameter: 3mm). We showed that S-CCI, at two injury severities, significantly decreased the neuroscore and produced deficits in performance on a rotarod device for the entire duration of the study. In contrast, the CCI induced motor deficits only at early stages after the injury, suggesting that the S-CCI model produces long-lasting motor deficits. Morris water maze test showed that both CCI and S-CCI produced persisting memory deficits. Furthermore, adhesive removal test showed significant somatosensory and motor deficits only in the S-CCI groups. Histological analysis showed a large extent of cortical contusion lesions, including both the sensory and motor cortex, and hippocampal damage in the S-CCI. These findings collectively suggest that the current model may offer sensitive, reliable, and clinically relevant outcomes for assessments of therapeutic strategies for TBI.