These findings extend the existing body of literature by making comparisons among species, gender, and injury model across cognitive and sensorimotor behavioral domains. We have also shown that cortical injuries, such as those induced by a traumatic brain injury, were associated with profound sensorimotor and cognitive deficits. In contrast, subcortical injuries, such as those induced by intracerebral hemorrhage, hypoxic-ischemia, or both, were associated with even more profound cognitive deficits in the absence of significant sensorimotor deficits. The observed patterns of performance indicate the similarities of the broad pattern of neurocognitive deficits associated with these rodent brain injury models and those observed following human brain injury.

Likewise, we observed subtle gender differences that proved to be species-dependent. As often reported in humans, males performed subtly, but significantly, better than females on a task of spatial learning. However, this phenomenon was only observed in rats, and mice of both genders performed more like female rats in the water maze. The opposite pattern was observed on a test of sensorimotor coordination and balance. In general, males performed subtly, but significantly, worse than females on the rotarod. However, this phenomenon was most evident in mice, and rats of both genders performed similarly to female mice. Although many studies from our laboratory have not found statistically significant differences in gender, these results suggest that consistent, but subtle, differences exist. Indeed, a meta-analysis of rodent sex differences by Jonasson [15] concluded that there was evidence for gender differences in spatial learning, despite the fact that the majority of reviewed studies reported no significant differences.

Finally, we observed that, in general, rats performed better across both cognitive and sensorimotor behavioral domains. However, as noted for spatial learning in the water maze, this was only true for male rats. For sensorimotor coordination and balance on the rotarod, only male mice performed worse than rats. These results at least partly corroborate those reported in the literature. When Wishaw and Tomie [32] used the water maze to assess spatial learning in rats and mice, rats performed significantly better. Moreover, the rats demonstrated improved problem-solving strategies over time relative to mice, indicating that they were learning to learn, whereas mice showed no such problem-solving strategy improvement. Even though strain differences have been observed in both rats [20] and mice [27] due to varying swim speeds and visual acuity, rats’ ability to conduct an organized search with high accuracy suggests that they are better problem solvers in the water. Even though it has been suggested that the Barnes maze, a dry land alternative to the water maze, may be more appropriate for mice, mice in our hands have performed similarly on both the Barnes maze and the water maze. Additionally, similar to our rotarod results, rats have demonstrated a greater ability to learn complex and coordinated asymmetrical motor behavior than mice in a test of reaching behavior and environmental manipulation [30].

Significant differences in task performance and trends in performance could indicate that particular species and gender combinations could provide better models for humans, or reveal the most important controls to consider, depending on the behavior of interest. Notably, gender differences were present, but were not the same for rats and mice. Mice demonstrated more pronounced gender differences in motor ability than rats, whereas rats demonstrated more pronounced gender differences in spatial learning. These findings have implications for study design. The extensive time and budget resources required for administration of a comprehensive battery requires that researchers use the most efficient design. Strategically designed batteries could identify initial behavioral outcomes and indicate the need for future behavioral testing while consuming the fewest resources. Depending on the nature of the injury and the deficits produced, the economic benefits of using mice over rats may be offset by the larger number of animals required to attain sufficient statistical power.

In summary, this study showed that the cognitive and sensorimotor abilities of rodents differ according to species, gender, and type of injury. This study also characterized distinct behavioral profiles for animals with cortical and subcortical brain injury models that resemble injury profiles in humans. Additional covariates, such as edema and lesion size, may further clarify these phenotypes. Overall, we provide evidence that abbreviated test batteries may be specifically designed to test deficits depending on the species, gender, and model.