Animal welfare assessment after controlled cortical impact in CD-1 mice - A model of posttraumatic epilepsy

The ethical use of laboratory animals requires that the benefits of an experimental study are carefully weighed against potential harm to the animals. In traumatic brain injury (TBI) research, ethical concerns are especially relevant to severe TBI, after which animals may experience suffering, depending on the implementation of refinement measures such as (1) postsurgical analgesia during the initial period following TBI and (2) humane endpoints. However, despite the frequent use of rodent models such as fluid percussion injury (FPI) and controlled cortical impact (CCI) in rats or mice, there is only one recent study that applied assessment of welfare to a severe TBI model, the FPI model in rats. In the present pilot study in a CCI mouse model of posttraumatic epilepsy, we assessed animal welfare by a brain injury-specific severity scoresheet. Furthermore, nest building was used as a sensitive indicator of health and welfare in laboratory mice. Sham mice that underwent craniotomy but not CCI were used for comparison. Craniotomy and CCI were performed under anesthesia with isoflurane, followed by 3 days of postsurgical analgesia with the opioid l-methadone. Mannitol was used to prevent the head pain caused by increased intracranial pressure. Using the TBI-specific scoresheet to describe and monitor potential distress in animals, moderately increased scores were determined in CCI mice only over the first 2 days after surgery, indicating that animal suffering in this model is transitory. Similarly, significantly impaired nest building was observed at 1 but not 7 days after CCI. We conclude that with effective postsurgical analgesia and mannitol behavioral recovery is rapid in mice after CCI.