Interaction between anesthesia, gender, and functional outcome task following diffuse traumatic brain injury in rats

A number of experimental and clinical studies have demonstrated that functional outcome following traumatic brain injury differs between males and females. Some studies report that females have a better outcome than males following trauma while others report the opposite. In experimental studies, some of the contradictory results may be due to the different experimental conditions, including type of anesthesia and the outcome measures employed. In the present study we have used three different anesthetic protocols and four different outcome measures to determine how these parameters interact and affect functional outcome following traumatic brain injury in male and female rats. Diffuse traumatic brain injury was induced in adult male and female animals using the impact-acceleration brain injury model. Mortality in female animals was no different than males when using halothane anesthesia, slightly better than males when using isoflurane anesthesia, but significantly worse than males under pentobarbital anesthesia. Female animals always performed better than males on rotarod tests of motor outcome, with this effect being unrelated to anesthetic effects. Conversely, in cognitive tests using the Barnes Maze, only isoflurane-anesthetized females performed better than their male counterparts. Similarly, in an open field activity task, females always performed better than males after trauma, with isoflurane-anesthetized females also performing significantly better than the halothane-anesthetized female group after injury. Our results suggest that female animals do better than males after diffuse traumatic brain injury, although this observation is dependent upon the type of anesthesia and the functional task employed. Isoflurane is particularly protective in females, pentobarbital is deleterious to female outcome, while halothane anesthesia has the least influence on gender-related outcome.