Optimization and validation of a modified radial-arm water maze protocol using a murine model of mild closed head traumatic brain injury
Optimization and validation of a modified radial-arm water maze protocol using a murine model of mild closed head traumatic brain injury
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DOI：
10.1371/journal.pone.0232862
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发表时间：
2020-08-18
期刊：
影响因子：
3.7
通讯作者：
Bachstetter, Adam D.
中科院分区：
文献类型：
--
作者：
Macheda, Teresa;Roberts, Kelly N.;Bachstetter, Adam D.
认知障碍可能是脑外伤（TBI）后的一个重大问题，每年影响全球数百万人。需要在啮齿动物中建立可重复的认知测定，以更好地理解疾病机制并开发治疗TBI诱导的损伤的治疗干预。我们的目标是验证和标准化的径向臂水迷宫（RAWM）测试作为一种检测，以筛选由TBI引起的认知障碍。RAWM是一种视觉空间学习测试，最初设计用于大鼠，后来适用于小鼠。本研究探讨了测试程序，如迷宫外线索的存在是否会影响学习和记忆的表现。使用四天方案在8臂RAWM中测试C57 BL/6小鼠。我们证明了两天的训练，将小鼠暴露于迷宫外的线索和可见的平台，影响了学习和记忆表现。与训练过的小鼠相比，未接受训练的小鼠表现较差。为了进一步验证我们的RAWM方案，我们使用东莨菪碱。我们还证明，一个单一的轻度闭合性颅脑损伤（CHI）造成赤字在这个任务后两周CHI。我们的数据支持使用每天7次试验和间隔训练方案作为揭示CHI后记忆障碍的关键因素。在这里，我们提供了一个详细的标准操作程序RAWM测试，它可以应用于各种小鼠模型，包括神经退行性疾病和病理，以及当使用药理学方法。
Cognitive impairments can be a significant problem after a traumatic brain injury (TBI), which affects millions worldwide each year. There is a need for establish reproducible cognitive assays in rodents to better understand disease mechanisms and to develop therapeutic interventions towards treating TBI-induced impairments. Our goal was to validate and standardize the radial arm water maze (RAWM) test as an assay to screen for cognitive impairments caused by TBI. RAWM is a visuo-spatial learning test, originally designed for use with rats, and later adapted for mice. The present study investigates whether test procedures, such us the presence of extra-maze cues influences learning and memory performance. C57BL/6 mice were tested in an 8-arm RAWM using a four-day protocol. We demonstrated that two days of training, exposing the mice to extra-maze cues and a visible platform, influenced learning and memory performance. Mice that did not receive training performed poorer compared to mice trained. To further validate our RAWM protocol, we used scopolamine. We, also, demonstrated that a single mild closed head injury (CHI) caused deficits in this task at two weeks post-CHI. Our data supported the use of 7 trials per day and a spaced training protocol as key factor to unmask memory impairment following CHI. Here, we provide a detailed standard operating procedure for RAWM test, which can be applied to a variety of mouse models including neurodegenerative diseases and pathology, as well as when pharmacological approaches are used.