Age, but not severity of injury, mediates decline in executive function: Validation of the rodent touchscreen paradigm for preclinical models of traumatic brain injury
Age, but not severity of injury, mediates decline in executive function: Validation of the rodent touchscreen paradigm for preclinical models of traumatic brain injury
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DOI：
10.1016/j.bbr.2019.111912
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发表时间：
2019-08-05
影响因子：
2.7
通讯作者：
Collins-Praino, Lyndsey E.
中科院分区：
文献类型：
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作者：
Arulsamy, Alina;Corrigan, Frances;Collins-Praino, Lyndsey E.
人们越来越认识到，创伤性脑损伤(TBI)不仅是一种急性事件，而且会导致持续的神经元损伤，可能导致多个认知领域的慢性损害。其中，执行功能缺陷是脑外伤后报告的更常见的变化之一，也是有脑外伤病史的个人的幸福感、社会功能和生活质量的主要预测指标。为了充分了解脑创伤和执行功能障碍之间的关系，包括可能解释这一现象的大脑机制，显然需要实验模型。然而，到目前为止，缺乏系统地比较损伤严重程度对执行功能的影响的临床前研究，特别是在损伤后的长期时间点。此外，许多以前的研究没有使用对损伤后可能表现出的全部执行功能损害敏感的行为测量，特别是在弥漫性轴突损伤模型中(Lv等人)。目前的研究目的是在DAI的实验模型中，研究不同程度的损伤后执行功能障碍演变的时间分布，最长可达12个月。为了做到这一点，我们利用啮齿动物触摸屏范式来管理5选项连续操作任务(5C-CPT)，这是5选项连续反应时间任务(5CSRT)的延伸。有趣的是，与假手术组相比，在损伤后1个月、6个月或12个月，无论损伤的最初严重程度如何，任何一组脑损伤组在学习、动机、注意力、反应时间或冲动方面都没有差异。相反，在12个月的时间点上看到的对执行功能的大部分影响似乎是年龄增长的结果，而不是伤害的结果。由于即使是12个月的时间点也代表着大鼠的中年，未来的研究将需要进一步探讨这些影响，以确定DAI是否可能影响老年执行功能障碍的表现。
Increasingly, it is being recognised that traumatic brain injury (TBI) is not just an acute event but instead results in ongoing neuronal injury that may lead to chronic impairments in multiple cognitive domains. Of these, deficits in executive function are one of the more common changes reported following TBI, and are a major predictor of well-being, social function and quality of life in individuals with a history of TBI. In order to fully understand the relationship between TBI and executive dysfunction, including brain mechanisms that may account for this, experimental models are clearly needed. However, to date, there have been a lack of preclinical studies systematically comparing the effect of injury severity on executive function, particularly at long-term timepoints post-injury. Furthermore, many previous studies have not used behavioural measures that are sensitive to the full range of executive function impairments that may manifest after injury, particularly in models of diffuse axonal injury (Lv et al.). The current study aimed to investigate the temporal profile, up to 12 months post-injury, of the evolution of executive dysfunction following different severities of injury in an experimental model of DAI. In order to do so, we utilised a rodent touchscreen paradigm to administer the 5 Choice Continuous Performance Task (5C-CPT), an extension of the 5-choice serial reaction time task (5CSRT). Interestingly, there were no differences in learning, motivation, attention, response time or impulsivity at 1 month, 6 months or 12 months post-injury in any of the TBI groups compared to sham, regardless of the initial severity of the injury. Instead, most of the effects on executive function seen at the 12 month timepoint appeared to be a result of ageing, not injury. As even the 12-month timepoint represents middle age in the rat, future studies will be needed to further probe these effects, in order to determine whether DAI may influence the presentation of executive dysfunction in older age.