Repetitive Mild Traumatic Brain Injury in Rats Impairs Cognition, Enhances Prefrontal Cortex Neuronal Activity, and Reduces Pre-synaptic Mitochondrial Function.
Repetitive Mild Traumatic Brain Injury in Rats Impairs Cognition, Enhances Prefrontal Cortex Neuronal Activity, and Reduces Pre-synaptic Mitochondrial Function.
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DOI：
10.3389/fncel.2021.689334
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发表时间：
2021
影响因子：
5.3
通讯作者：
Pan B
中科院分区：
文献类型：
--
作者：
Feng Y;Li K;Roth E;Chao D;Mecca CM;Hogan QH;Pawela C;Kwok WM;Camara AKS;Pan B
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mTBI后长期认知障碍的已知机制。重复设计旋转加速度的闭合头部撞击模型（rCHIMERA）是重复mTBI（rmTBI）的非手术动物模型，模拟了人类rmTBI的关键特征。使用大鼠rCHIMERA，本研究旨在表征rmTBI诱导的行为中断，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。大鼠在2天内以2焦耳的能量接受6次闭头撞击。行为测试包括在开放领域和家庭笼环境中的行为自动分析，旋转棒测试运动技能，新的物体识别，和恐惧条件反射。在rmTBI之后，大鼠花费更少的时间梳理并且在开放场地竞技场的中心花费更少的时间。在mTBI后1周，在其家笼中的大鼠减少了不活动时间，并在损伤后1个月增加了探索时间。rmTBI后4周，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时记忆减少。单单位在体内记录显示，增加神经元活动的mPFC后rmTBI，部分归因于神经元去抑制减少抑制性突触传递，可能继发于受损的线粒体功能。这些发现有助于验证这种大鼠rmTBI模型复制临床特征，并指出损伤后线粒体功能受损导致突触传递不平衡和随后的长期认知功能障碍受损。
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.
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影响因子：
15.9
作者：
Gilmartin MR;Balderston NL;Helmstetter FJ
通讯作者：
Helmstetter FJ
影响因子：
2.5
作者：
Ji, Guangchen;Neugebauer, Volker
通讯作者：
Neugebauer, Volker
影响因子：
2
作者：
Gilmartin, Marieke R.;Helmstetter, Fred J.
通讯作者：
Helmstetter, Fred J.
影响因子：
5.3
作者：
Haar, Cole Vonder;Martens, Kris M.;Wellington, Cheryl L.
通讯作者：
Wellington, Cheryl L.
影响因子：
16.2
作者：
Euston DR;Gruber AJ;McNaughton BL
通讯作者：
McNaughton BL