Deficits in Social Behavior Emerge During Development After Pediatric Traumatic Brain Injury in Mice

The pediatric brain may be particularly vulnerable to social deficits after traumatic brain injury (TBI) due to the protracted nature of psychosocial development through adolescence. However, the majority of pre-clinical studies fail to assess social outcomes in experimental pediatric TBI. The current study evaluated social behavior in mice subjected to TBI at post-natal day (p)21. Social behaviors were assessed by a partition test, resident-intruder, three-chamber, and tube dominance tasks during adolescence (p35-42) and again during early adulthood (p60-70), during encounters with unfamiliar, naïve stimulus mice. Despite normal olfactory function and normal social behaviors during adolescence, brain-injured mice showed impaired social investigation by adulthood, evidenced by reduced ano-genital sniffing and reduced following of stimulus mice in the resident-intruder task, as well as a loss of preference for sociability in the three-chamber task. TBI mice also lacked a preference for social novelty, suggestive of a deficit in social recognition or memory. By adulthood, brain-injured mice exerted more frequent dominance in the tube task compared to sham-operated controls, a finding suggestive of aggressive tendencies. Together these findings reveal reduced social interaction and a tendency towards increased aggression, which evolves across development to adulthood. This emergence of aberrant social behavior, which parallels the development of other cognitive deficits in this model and behaviors seen in brain-injured children, is consistent with the hypothesis that the full extent of deficits is not realized until the associated skills reach maturity. Thus, efficacy of therapeutics for pediatric TBI should take into account the time-dependent emergence of abnormal behavioral patterns.