A major hurdle preventing effective interventions for patients with mild traumatic brain injury (mTBI) is the lack of known mechanisms for the long-term cognitive impairment that follows mTBI. The closed head impact model of repeated engineered rotational acceleration (rCHIMERA), a non-surgical animal model of repeated mTBI (rmTBI), mimics key features of rmTBI in humans. Using the rCHIMERA in rats, this study was designed to characterize rmTBI-induced behavioral disruption, underlying electrophysiological changes in the medial prefrontal cortex (mPFC), and associated mitochondrial dysfunction. Rats received 6 closed-head impacts over 2 days at 2 Joules of energy. Behavioral testing included automated analysis of behavior in open field and home-cage environments, rotarod test for motor skills, novel object recognition, and fear conditioning. Following rmTBI, rats spent less time grooming and less time in the center of the open field arena. Rats in their home cage had reduced inactivity time 1 week after mTBI and increased exploration time 1 month after injury. Impaired associative fear learning and memory in fear conditioning test, and reduced short-term memory in novel object recognition test were found 4 weeks after rmTBI. Single-unit in vivo recordings showed increased neuronal activity in the mPFC after rmTBI, partially attributable to neuronal disinhibition from reduced inhibitory synaptic transmission, possibly secondary to impaired mitochondrial function. These findings help validate this rat rmTBI model as replicating clinical features, and point to impaired mitochondrial functions after injury as causing imbalanced synaptic transmission and consequent impaired long-term cognitive dysfunction.

中文翻译：

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大鼠重复性轻度创伤性脑损伤损害认知，增强前额叶皮层神经元活动，并降低突触前线粒体功能。

阻碍对轻度创伤性脑损伤 (mTBI) 患者进行有效干预的一个主要障碍是缺乏已知的 mTBI 后长期认知障碍的机制。重复工程旋转加速度 (rCHIMERA) 的封闭头部冲击模型是重复 mTBI (rmTBI) 的非手术动物模型，模仿人类 rmTBI 的关键特征。在大鼠中使用 rCHIMERA，本研究旨在表征 rmTBI 诱导的行为破坏、内侧前额叶皮层 (mPFC) 的潜在电生理变化以及相关的线粒体功能障碍。在 2 焦耳的能量下，大鼠在 2 天内接受了 6 次闭合头部撞击。行为测试包括开放场地和家庭笼子环境中行为的自动分析、运动技能的旋转测试、新物体识别和恐惧条件反射。在 rmTBI 之后，大鼠在露天场地中心花费更少的时间梳理和更少的时间。在家笼中的大鼠在 mTBI 后 1 周减少了不活动时间，并在受伤后 1 个月增加了探索时间。在 rmTBI 后 4 周发现恐惧条件反射测试中的联想恐惧学习和记忆受损，新物体识别测试中的短期记忆减少。单单位体内记录显示 rmTBI 后 mPFC 中的神经元活动增加，部分归因于抑制性突触传递减少导致的神经元去抑制，可能继发于线粒体功能受损。这些发现有助于验证这种大鼠 rmTBI 模型是否可以复制临床特征，