Sex-specific cognitive effects of mild traumatic brain injury to the frontal and temporal lobes

Background: Cognitive deficits are the most enduring and debilitating sequelae of mild traumatic brain injury (mTBI). However, relatively little is known about whether the cognitive effects of mTBI vary with respect to time post-injury, biological sex, and injury location.Objectives: The aim of this study was to assess the effect of the side and site of mTBI and to determine whether these effects are sexually dimorphic.Methods: Male and female ICR mice were subjected to either a sham procedure or mTBI to the temporal lobes (right-sided or left-sided) or to the frontal lobes (bilateral) using a weight-drop model. After recovery, mice underwent a battery of behavioral tests at two post-injury time points.Results: Different mTBI impact locations produced dissociable patterns of memory deficits; the extent of these deficits varied across sexes, time points, and memory domains. In both sexes, frontal mTBI mice exhibited a delayed onset of spatial memory deficits. Additionally, the performance of the frontal and left temporal injured males and females was more variable than that of controls. Interestingly, only in females does the effect of mTBI on visual recognition memory depend on the time post-injury. Moreover, only in females does spatial recognition memory remain relatively intact after mTBI to the left temporal lobe.Conclusion: This study showed that different mTBI impact sites produce dissociable and sex-specific patterns of cognitive deficits in mice. The results emphasize the importance of considering the injury site/side and biological sex when evaluating the cognitive sequelae of mTBI.