A Clinically Relevant Mouse Model of Concussion Incorporating High Rotational Forces.

IF 1.8 Q3 CLINICAL NEUROLOGY
Neurotrauma reports Pub Date : 2025-02-17 eCollection Date: 2025-01-01 DOI:10.1089/neur.2024.0165
Elizabeth M Teasell, Emilie Potts, Nicole Geremia, Lihong Lu, Xiaoyun Xu, Haojie Mao, Arthur Brown
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引用次数: 0

Abstract

Clinically relevant models of concussion are critical in understanding the pathophysiology of concussion and its long-term outcomes. To bridge the gap between preclinical and clinical research, animal models of concussion should be produced by mild traumatic brain injuries (mTBIs) that possess the same physical and biomechanical properties found in the mTBIs that cause concussion in humans. Specifically, to have good construct validity the mTBIs used in animal models of concussion should feature closed-head impacts with unrestrained head and body motion, resulting in peak angular velocities that approximate the human experience. We describe a mouse model of concussion using a cortical impactor to deliver closed-head mTBIs. Mice are placed on a break-away platform that allows free head and body movement during and after impact resulting in rapid head rotation. We assessed this model of concussion in over 100 mice carrying humanized versions of the genes encoding the amyloid precursor protein and tau. We found that this method consistently produced injuries with peak angular velocities in mice that, when scaled, approximated the average peak angular velocities reported in concussive football impacts. Face validity of this model of concussion was evaluated by histopathology and revealed that three impacts delivered 24 hours apart led to diffuse axonal injury, astrogliosis, and microglial activation one week after injury, particularly in white matter tracts aligned orthogonally to the axis of rotation. Persistent axonal degeneration was observed up to 6 months postinjury. This mouse model of concussion captures key biomechanical and pathological features of human concussions.

一种具有临床意义的高旋转力脑震荡小鼠模型。
脑震荡的临床相关模型对于理解脑震荡的病理生理学及其长期预后至关重要。为了弥合临床前和临床研究之间的差距,脑震荡的动物模型应该由轻度创伤性脑损伤(mTBIs)产生,该模型具有与引起人类脑震荡的mTBIs相同的物理和生物力学特性。具体而言,为了具有良好的构建效度,用于脑震荡动物模型的mtbi应该具有封闭式头部碰撞,头部和身体运动不受约束,从而产生接近人类经验的峰值角速度。我们描述了一个使用皮质撞击器传递闭头mtbi的小鼠脑震荡模型。老鼠被放置在一个分离的平台上,在撞击期间和之后,可以自由地移动头部和身体,从而导致头部快速旋转。我们在100多只携带编码淀粉样蛋白前体蛋白和tau蛋白的人源化基因的小鼠中评估了这种脑震荡模型。我们发现,这种方法在小鼠身上始终产生峰值角速度的损伤,当按比例计算时,其峰值角速度近似于报道的脑震荡橄榄球撞击的平均峰值角速度。通过组织病理学对该脑震荡模型的面部有效性进行了评估,结果显示,间隔24小时的三次撞击导致弥漫性轴索损伤、星形胶质细胞增生和损伤后一周的小胶质细胞激活,特别是在与旋转轴垂直排列的白质束中。损伤后6个月观察到持续性轴突变性。这种小鼠脑震荡模型捕捉了人类脑震荡的关键生物力学和病理特征。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.40
自引率
0.00%
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0
审稿时长
8 weeks
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