Pre-Clinical Models of Penetrating Brain Injury: Study Protocol for a Scoping Review.

Penetrating brain injuries (PBI) constitute a significant subset of traumatic brain injuries, characterized by high morbidity and mortality due to their unique pathophysiological mechanisms. Despite its clinical prevalence in civilian and military settings, progress in translational research remains limited due to a lack of well-characterized pre-clinical models that accurately replicate human PBI. Existing models often fail to adequately simulate critical aspects such as ballistic dynamics, tissue cavitation, and secondary injury cascades, limiting their translational relevance and hindering therapeutic advancements. This scoping review aims to systematically evaluate existing pre-clinical models, including animal, computational, ballistic, and hybrid simulations, to assess their methodological rigor, translational applicability and reported outcome measures. Using PRISMA-ScR guidelines, we will conduct a comprehensive literature search across multiple databases, extracting data on model characteristics, injury induction techniques, histopathological findings, biomolecular markers, and functional assessments. Additionally, bibliometric analyses will provide insights into research trends and gaps in PBI modeling, particularly concerning replicating real-world injury mechanisms and long-term functional outcomes. Through this evaluation, we aim to identify optimal experimental frameworks for studying PBI pathophysiology and recovery mechanisms while informing future model development for therapeutic advancements. The findings from this review will serve as a foundation for advancing pre-clinical PBI research, guiding future model development and therapeutic innovations, and ultimately enhancing treatment strategies and patient outcomes.