Sex-dependent changes in neuronal morphology and psychosocial behaviors after pediatric brain injury.

Chronic social behavior problems after pediatric traumatic brain injury (TBI) significantly contribute to poor quality of life for survivors. Using a well-characterized mouse model of early childhood TBI, we have previously demonstrated that young brain-injured mice develop social deficits by adulthood. As biological sex may influence both normal and aberrant social development, we here evaluated potential sex differences in post-TBI psychosocial deficits by comparing the behavior of male and female mice at adulthood (8 weeks post-injury). Secondly, we hypothesized that pediatric TBI would influence neuronal morphology identified by Golgi-Cox staining in the hippocampus and prefrontal cortex, regions involved in social cognition and behavior, before the onset of social problems (3 weeks post-injury). Morphological analysis of pyramidal neurons in the ipsilateral prefrontal cortex and granule cells of the hippocampal dentate gyrus revealed a reduction in dendritic complexity after pediatric TBI. This was most apparent in TBI males, whereas neurons from females were less affected. At adulthood, consistent with previous studies, TBI males showed deficits in sociability and social recognition. TBI females also showed a reduction in sociability, but intact social recognition and increased sociosexual avoidance. Together, these findings indicate that sex is a determinant of regional neuroplasticity and social outcomes after pediatric TBI. Reduced neuronal complexity in the prefrontal cortex and hippocampus, several weeks after injury in male mice, appears to precede the subsequent emergence of social deficits. Sex-specific alterations in the social brain network are thus implicated as an underlying mechanism of social dysfunction after pediatric TBI.