Department of Neuroscience, Monash University, Melbourne, Victoria, Australia.
Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia.
J Neurotrauma. 2020 Nov 15;37(22):2381-2400. doi: 10.1089/neu.2018.6149. Epub 2019 May 24.
Traumatic brain injury (TBI) is a leading cause of morbidity worldwide, with patients often suffering from consequences such as cognitive deficits, social abnormalities, anxiety, depression, pain, and motor dysfunction. Given that these impairments often have a significant impact on the patient's quality of life, a key aim of therapeutic intervention in TBI is to mitigate these effects. Translational strategies to develop such interventions have heavily featured animal models of TBI. To assess the efficacy of interventions in these models, a range of behavioral outcomes are utilized. However, in light of the past translational failures that have plagued the TBI field, the clinical relevance of these preclinical behavioral tests is now being scrutinized. This article will summarize the behavioral consequences of TBI in humans; describe common methods available for testing cognition, social function, motor ability, pain, as well as depression- and anxiety-like behaviors in animal models of TBI; provide an overview of the results from TBI animal model studies that have utilized these methods; and discuss these pre-clinical behavior methods and findings in terms of their relevance to the clinical TBI setting. We conclude that there is translational value in these methods and their related findings, but also suggest strategies and future research to improve the clinical relevance of behavior testing in animal models of TBI.
创伤性脑损伤（TBI）是全球范围内发病率较高的疾病之一，患者常伴有认知障碍、社会异常、焦虑、抑郁、疼痛和运动功能障碍等后果。鉴于这些损伤通常对患者的生活质量有重大影响，TBI 治疗干预的一个关键目标是减轻这些影响。开发这些干预措施的转化策略主要以 TBI 的动物模型为特色。为了评估这些模型中干预措施的效果，使用了一系列行为结果。然而，鉴于过去困扰 TBI 领域的转化失败，这些临床前行为测试的临床相关性现在正在受到审查。本文将总结 TBI 对人类的行为后果；描述在 TBI 动物模型中测试认知、社会功能、运动能力、疼痛以及抑郁和焦虑样行为的常用方法；概述使用这些方法的 TBI 动物模型研究的结果；并根据其与临床 TBI 环境的相关性讨论这些临床前行为方法和发现。我们得出的结论是，这些方法及其相关发现具有转化价值，但也提出了提高 TBI 动物模型行为测试临床相关性的策略和未来研究。
