Abstract
BACKGROUND: Examining the role of sex on recovery from pediatric TBI (pTBI) is a complex task, specifically when referring to injuries occurring during critical developmental and maturation periods. The effect of sex hormones on neurological and neuropsychiatric outcomes has been studied among adult TBI females, but not in children. During development, puberty is considered a key milestone accompanied by changes in physical growth, neuronal maturation, sex hormones, and psychological symptoms. Following pTBI, such changes might have a significant effect on brain re-organization and on long-term neuropsychiatric outcomes. While hormonal dysfunction is a common consequence following pTBI, only few studies have systematically evaluated hormonal changes following pTBI. AIMS: To describe a multimodal protocol aimed to examine the effect of puberty on brain connectivity and long-term neuropsychiatric outcomes following TBI in female girls and adolescents. METHODS: A case-control longitudinal prospective design will be used. 120 female participants aged 9 to 16 years (N = 60 per group) will be recruited. In the acute phase (T0-1 month), participants will undergo an MRI protocol for brain connectivity, as well as a clinical evaluation for puberty stage and hormonal levels. In the chronic phase (T1-18-24 months), participants will complete a neuropsychiatric assessment in addition to the MRI and puberty evaluations. Hormonal levels will be monitored at T0 and T1. A moderation-mediation model will be used to examine the moderating effects of puberty on the association between pTBI and neuropsychiatric symptoms in female girls and adolescents, through the mediating effect of brain network connectivity. SIGNIFICANCE: This study will highlight sex-specific factors related to outcomes among females following pTBI and enhance our understanding of the unique challenges they face. Such information has a substantial potential to guide future directions for research, policy and practice.