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Introduction- In the United States, traumatic brain injuries (TBIs) are a leading cause of death in children, with 0-3 years old being the most vulnerable population due to the risk of falling and abuse. Although the prevalence of pediatric TBIs is high, they are vastly underrepresented in pre-clinical models. This alarming reality contributes to the lack of understanding of how even mild TBIs (mTBI) affect brain development. It is my working hypothesis that pediatric mTBI results in gliosis, which disrupts critical neurodevelopmental processes such as microglial-regulated synaptic pruning and delays various behavioral milestone achievements.

Methods- To test my hypothesis, a previously published pediatric mTBI model from the Fleiss lab was adopted. Mice weighing 3.5–4.0 g underwent a mild weight drop TBI or sham injury paradigm testing three different injury intensities. To evaluate injury-induced pathologies, phenotypes of the injured ipsilateral side to the non-injured contralateral side from injured and sham brains from all four groups were compared. Gliosis was assessed by immunohistological stains: Iba-1 and GFAP. To determine if the complement system was inappropriately activated following injury, complement proteins associated with synaptic pruning, Clq and C3, were measured. Additionally, to evaluate behaviors typically reached during development, behavioral milestone paradigms and isolated ultrasonic vocalizations were performed on mice following TBI or sham injury.

Results - Although there are no overt signs of gliosis, there is greater complement system activation in mTBI mice than sham mice. Western blot data showed that there may be increased synaptic pruning in the injured side compared to the non-injured side as shown by increased C1q and C3 levels. Behavioral testing results show that mTBI mice exhibit developmental milestone delays and communication deficits when compared to sham mice. Furthermore, the most severe injury grade resulted in the most dramatic injury pathologies and behavioral deficits.

Conclusion- These findings improve our understanding of mTBI glial mechanisms and their impact during postnatal development.