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雄性大鼠重复性闭合性颅脑损伤会损害注意力,但在冲动性和神经胶质病理的多项测量中会导致异质性结果。

Repeat Closed-Head Injury in Male Rats Impairs Attention but Causes Heterogeneous Outcomes in Multiple Measures of Impulsivity and Glial Pathology.

作者信息

Vonder Haar Cole, Wampler Sarah K, Bhatia Henna S, Ozga Jenny E, Toegel Cory, Lake Anastasios D, Iames Christopher W, Cabral Caitlyn E, Martens Kris M

机构信息

Injury and Recovery Laboratory, Department of Neuroscience, Ohio State University, Columbus, OH, United States.

Injury and Recovery Laboratory, Department of Psychology, West Virginia University, Morgantown, WV, United States.

出版信息

Front Behav Neurosci. 2022 Mar 11;16:809249. doi: 10.3389/fnbeh.2022.809249. eCollection 2022.

DOI:10.3389/fnbeh.2022.809249
PMID:35359588
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8963781/
Abstract

Repetitive mild traumatic brain injury, or concussion, can lead to the development of long-term psychiatric impairments. However, modeling these deficits is challenging in animal models and necessitates sophisticated behavioral approaches. The current set of studies were designed to evaluate whether a rubberized versus metal impact tip would cause functional deficits, the number of injuries required to generate such deficits, and whether different psychiatric domains would be affected. Across two studies, male rats were trained in either the 5-choice serial reaction time task (5CSRT; Experiment 1) to assess attention and motor impulsivity or concurrently on the 5CSRT and the delay discounting task (Experiment 2) to also assess choice impulsivity. After behavior was stable, brain injuries were delivered with the Closed-head Injury Model of Engineered Rotational Acceleration (CHIMERA) either once per week or twice per week (Experiment 1) or just once per week (Experiment 2). Astrocyte and microglia pathology was also assayed in relevant regions of interest. CHIMERA injury caused attentional deficits across both experiments, but only increased motor impulsivity in Experiment 1. Surprisingly, choice impulsivity was actually reduced on the Delay Discounting Task after repeat injuries. However, subsequent analyses suggested potential visual issues which could alter interpretation of these and attentional data. Subtle changes in glial pathology immediately after the injury (Experiment 1) were attenuated after 4 weeks recovery (Experiment 2). Given the heterogenous findings between experiments, additional research is needed to determine the root causes of psychiatric disturbances which may arise as a results of repeated brain injuries.

摘要

重复性轻度创伤性脑损伤,即脑震荡,可导致长期精神障碍的发展。然而,在动物模型中模拟这些缺陷具有挑战性,需要复杂的行为学方法。当前的一系列研究旨在评估橡胶撞击尖端与金属撞击尖端是否会导致功能缺陷、产生这些缺陷所需的损伤次数,以及不同的精神领域是否会受到影响。在两项研究中,雄性大鼠接受了5选串行反应时任务(5CSRT;实验1)训练以评估注意力和运动冲动性,或者同时接受5CSRT和延迟折扣任务(实验2)训练以评估选择冲动性。行为稳定后,使用工程旋转加速度闭合性脑损伤模型(CHIMERA)每周一次或每周两次(实验1)或仅每周一次(实验2)给予脑损伤。还在相关感兴趣区域检测了星形胶质细胞和小胶质细胞病理学。CHIMERA损伤在两个实验中均导致注意力缺陷,但仅在实验1中增加了运动冲动性。令人惊讶的是,重复损伤后延迟折扣任务中的选择冲动性实际上降低了。然而,随后的分析表明存在潜在的视觉问题,这可能会改变对这些数据和注意力数据的解释。损伤后立即出现的胶质细胞病理学细微变化(实验1)在恢复4周后减弱(实验2)。鉴于实验之间的结果存在异质性,需要进一步研究以确定反复脑损伤可能导致的精神障碍的根本原因。

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Blood-brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks.血脑屏障破坏和脑室扩大是反复亚脑震荡打击 2 周以上大鼠最早的神经病理学变化。
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Chronic lipopolysaccharide impairs motivation when delivered to the ventricles, but not when delivered peripherally in male rats.慢性脂多糖经脑室给药会损害雄性大鼠的动机,但经外周给药则不会。
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J Neurotrauma. 2021 Jun 1;38(11):1585-1606. doi: 10.1089/neu.2021.0025. Epub 2021 Apr 28.
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Repeated Long-Term Sub-concussion Impacts Induce Motor Dysfunction in Rats: A Potential Rodent Model.反复长期轻度脑震荡撞击导致大鼠运动功能障碍:一种潜在的啮齿动物模型。
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