Pre-clinical models of disease have long played important roles in the advancement of new treatments. However, in traumatic brain injury (TBI), despite the availability of numerous model systems, translation from bench to bedside remains elusive. Integrating clinical relevance into pre-clinical model development is a critical step toward advancing therapies for TBI patients across the spectrum of injury severity. Pre-clinical models include in vivo and ex vivo animal work—both small and large—and in vitro modeling. The wide range of pre-clinical models reflect substantial attempts to replicate multiple aspects of TBI sequelae in humans. Although these models reveal multiple putative mechanisms underlying TBI pathophysiology, failures to translate these findings into successful clinical trials call into question the clinical relevance and applicability of the models. Here, we address the promises and pitfalls of pre-clinical models with the goal of evolving frameworks that will advance translational TBI research across models, injury types, and the heterogenous etiology of pathology.

中文翻译：

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推进创伤性脑损伤临床前科学的路线图

疾病的临床前模型长期以来在新疗法的发展中发挥着重要作用。然而，在创伤性脑损伤 (TBI) 中，尽管有许多模型系统可用，但从工作台到床边的转换仍然难以捉摸。将临床相关性整合到临床前模型开发中是推进针对不同损伤严重程度的 TBI 患者的治疗的关键一步。临床前模型包括体内和离体动物工作——无论大小——以及体外造型。广泛的临床前模型反映了在人类中复制 TBI 后遗症的多个方面的大量尝试。尽管这些模型揭示了 TBI 病理生理学的多种推定机制，但未能将这些发现转化为成功的临床试验，这对模型的临床相关性和适用性提出了质疑。在这里，我们解决了临床前模型的承诺和缺陷，目标是发展框架，推动跨模型、损伤类型和病理异质病因学的转化 TBI 研究。