Physical exercise as a cognitive rehabilitation treatment after traumatic brain injury: Intensity- and sex-dependent effects.

We investigated the effects of forced physical exercise (PE) intensity on cognitive dysfunction and histological changes associated with traumatic brain injury (TBI), in both male and female rats. Controlled cortical impact (CCI) produced similar short- and long-term memory deficits in both sexes, and these deficits were associated with reduced volume and neuronal loss in the hippocampus, but not with changes in neurogenesis. We found sex differences in the effects of intensity of forced PE on cognitive recovery: all PE intensities tested improved short-term memory in both sexes, but to a greater extent in females, while long-term memory benefits were intensity- and sex-dependent. Males benefited most from low-intensity PE, while females showed optimal results at moderate intensity. These optimal PE intensities increased the neurogenesis in both sexes. A neuroprotective effect of low-intensity PE was evident in males, but no effect was observed in females. These findings suggest an intensity- and sex-specific effect of PE post-TBI, emphasizing the need for tailored PE protocols based on sex to enhance therapeutic outcomes.