Mild pediatric traumatic brain injury has sex-specific effects on neuroimmune cells and social behavior in rats

Pediatric traumatic brain injury (TBI) increases the risk for long-term physical, cognitive, and psychosocial changes, many of which can lead to challenges in daily life functioning. Our understanding of how pediatric TBI interferes with brain development to lead to long-term behavioral outcomes is still incomplete. Despite emerging evidence for sex-specific outcomes in people, few rodent studies have examined sex differences after pediatric TBI. Here, we investigated the impact of pediatric lateral fluid percussion injury on acute neuroimmune and chronic neurobehavioral outcomes in male and female Sprague Dawley rats. At 3 days post injury (DPI), both sham and TBI increased microglia immunoreactivity relative to naive controls and had sex-specific effects on astrocytes. TBI increased brain mast cells relative to naive controls at 3 DPI in both sexes, and this increase persisted in females at 7 DPI. Sham and TBI procedures increased juvenile social play behavior in males and rearing behavior in both sexes relative to naive controls. Pediatric TBI reduced adult social interaction and had sex-differential effects on social avoidance, with increased avoidance in TBI females and decreased avoidance in TBI males. Injury condition did not affect perineuronal nets or oxytocin immunoreactivity at 7 DPI or oxytocin in adulthood. These studies show that immune cells in the male and female brain are differentially sensitive to the acute and sub-acute neuroinflammatory consequences of pediatric head trauma, and that pediatric head trauma in rats has age- and sex-dependent consequences for social behavior.