Wong Cindy K, Dinalo Jennifer E, Lyden Patrick D, Sung Gene, Poblete Roy A
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Norris Medical Library, University of Southern California, Los Angeles, CA 90033, USA.
NeuroSci. 2025 Apr 30;6(2):37. doi: 10.3390/neurosci6020037.
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.
穿透性脑损伤（PBI）是创伤性脑损伤的一个重要子集，因其独特的病理生理机制而具有高发病率和死亡率。尽管其在 civilian 和军事环境中临床常见，但由于缺乏能够准确复制人类 PBI 的特征明确的临床前模型，转化研究进展仍然有限。现有模型往往无法充分模拟诸如弹道动力学、组织空化和继发性损伤级联反应等关键方面，限制了它们的转化相关性并阻碍了治疗进展。本综述旨在系统评估现有的临床前模型，包括动物、计算、弹道和混合模拟，以评估其方法的严谨性、转化适用性和报告的结果指标。使用 PRISMA-ScR 指南，我们将在多个数据库中进行全面的文献检索，提取有关模型特征、损伤诱导技术、组织病理学发现、生物分子标志物和功能评估的数据。此外，文献计量分析将提供有关 PBI 建模研究趋势和差距的见解，特别是关于复制现实世界损伤机制和长期功能结果的方面。通过此次评估，我们旨在确定研究 PBI 病理生理学和恢复机制的最佳实验框架，同时为未来治疗进展的模型开发提供信息。本综述的结果将为推进临床前 PBI 研究、指导未来模型开发和治疗创新奠定基础，并最终改善治疗策略和患者预后。 （注：原文中“civilian”可能有误，推测可能是“civil”，但按要求未作修改。）
