Name: a mouse model of single and repetitive mild traumatic brain injury
Uploaded: 2017-06-20T12:30:00.000+00:00
Duration: 4 min 19 s
Description: Watch this Scientific Journal Video about A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury at JoVE.com

这项工作得到了国家神经病学和中风研究所（MPB）的R01 NS067417的支持。

这些研究严格按照"国家卫生研究院实验动物护理和使用指南"中的建议进行。该协议经乔治敦大学机构动物保护和使用委员会批准。将小鼠饲养在温度控制的动物设施中，并保持在12小时光/ 12小时黑暗循环。食物和水随意提供 。 1.制备mTBI仪器注意:mTBI设备包括一个控制冲击参数的数据采集（DAQ）箱，一个执行冲击的高速气动冲击器，以及一个模制的凝胶填充底座，使冲击后头部减速。 <ol><li>打开压缩空气，并将高速气动冲击器初始化为861.85 kPa的压力。 </li><li>将DAQ控制系统校准到以下参数 - 活塞速度为2.35 m / s，表面停留时间e为31.5 ms。 </li><li>将模制的凝胶填充底座（可压缩性64 kPa / mm）放置成中线与冲击器尖端的轨迹垂直。 </li></ol> mTBI冲击<ol><li>记录所有使用的小鼠的体重。 </li><li>在诱导室中麻醉3％异氟烷在氧气中120s的小鼠。 </li><li>将小鼠转移到mTBI装置，通过柔韧的非固定鼻锥继续麻醉。 </li><li>在鼻锥中，将鼠标头放在凝胶垫上，使得颅骨的平坦表面垂直于冲击器尖端呈现。 </li><li>将胶带放在鼠标头上，以创建一个平坦的表面，并将耳朵远离冲击部位。 </li><li>降低聚四氟乙烯冲击器尖端以与头部中心的矢状中线对齐。使用的冲击器尖端直径为10mm，将覆盖从眼睛后面到耳朵中线的头皮区域。调整冲击器，这样就可以了st触摸鼠标头的表面。 </li><li>收回冲击头，并手动拨下所需的偏转深度（7.5 mm）。 </li><li>控制DAQ控制系统，并按下触发按钮来影响鼠标头，或者是单一或重复的影响。重复的影响在每次影响之间不间断地交付。 </li><li>在最终冲击后立即将麻醉和mTBI装置的鼠标移开，并置于仰卧位。 </li><li>使用秒表测量正确反射（仰卧俯仰）返回的延迟，以确定意识时间的消失以及行走时间（无阻碍的行走）。 </li><li>监视鼠标并恢复正常行为，返回到其家中的笼子。 </li><li>假小鼠接受相同的处理和麻醉，但不受影响。 </li></ol>

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作者没有什么可以披露的。

在人类中，mTBI的特征在于没有结构性损伤的功能障碍。这可能与意识丧失有关，或没有意识丧失1 。目前认为接触重复脑震荡是神经变性疾病如CTE 4发展和/或发展的基础。据了解，CTE通常在拳击手和足球运动员中被发现，尽管暴露于重复脑震荡（包括不导致意识丧失的人）被认为是开发CTE的基本要素，但我们还不知道为什么重复脑震荡引起大脑中发生明显变化?...

创伤性脑损伤（TBI）被定义为由外部物理力量持续的头部损伤，导致正常脑功能的破坏。它代表了重大的社会经济和公共卫生负担，"国际疾病预防控制中心2015年报告"向国会估计，每年有250万美国人维持TBI。这不仅影响了患者的生活质量，而且对社会造成极高的经济成本，目前估计每年为765亿美元。传达的实际脑损伤的数量和急性期症状是定义轻度，中度和重度TBI。 轻度创伤性脑损伤（mTBI）也被称为脑震荡，占每年报告的TBI的70％以上1 。参加拳击和足球2高风险接触运动的运动员最常见。不像中度或严重形式的TBI，与mTBI相关的直接损害和症状有时不明显3 。相比之下，mTBI的长期影响可能与中度和重度形式的长期影响一样虚弱。患有重复mTBI的患者已被证明会发展为慢性创伤性脑病（CTE），以及其他认知和退行性疾病。因此，重要的是要进一步了解有助于mTBI之后产生的短期症状和总体长期损害的机制。 在人类中，第四届国际体育冲击大会（苏黎世2012）定义的脑震荡定义5指出，体育震荡的伤害程度轻微，不会造成严重的病理变化，但确实造成短期神经功能缺损这是自发解决的。事实上，研究调查了使用头撞式遥测系统，mTBI对高中足球运动员认知障碍的影响。这项研究显示，在一个赛季，玩家持续头盔影响&gt; 20g的次数从226人（平均每场4.7次）的高点到1855年（平均每场38.6次） 6次 。大多数这些影响并不导致脑震荡的临床诊断;但是使用fMRI 6可以观察到脑功能的功能变化的证据。导致这些功能变化的大脑变化是未知的，因此迫切需要有一个可靠和可重复的模型，以便于研究震荡和次冲击性mTBI的影响。 尽管以前尝试在小鼠和老鼠中建模mTBI 7 ，但许多报告不良反应。特别是，大多数啮齿动物模型的重复性质受到限制5 mTBIs的影响，以及不良的病理事件，包括脑内出血，颅骨骨折，严重的轴突损伤，神经元细胞死亡和增加的死亡率8,9,10,11,12。在这里，我们描述了更接近人类脑震荡真正定义的mTBI的小鼠模型。该模型概括了人类mTBI中观察到的许多症状，例如导致意识暂时丧失的机械力，没有明显的大脑病理学。此外，有利的是，它可以用于长时间段的单次冲击和重复冲击范例，如前所述13 。

<table><tbody><tr><td>Powerlab 8SP data acquisition (DAQ) control box&amp;nbsp;</td><td>(AD instruments)</td><td></td><td></td></tr><tr><td>VIP 3000 calibrated vaporizer</td><td>Matrx</td><td></td><td></td></tr><tr><td>Isoflurane</td><td>Henry Schein Animal Health</td><td>29405</td><td></td></tr><tr><td>Oxygen</td><td></td><td></td><td>Commercially available</td></tr><tr><td>Compressed Air</td><td></td><td></td><td>Commercially available</td></tr><tr><td>Masking Tape</td><td></td><td></td><td>Commercially available</td></tr><tr><td>Stop Watch</td><td>Fisher Scientific</td><td>02-261-840</td><td></td></tr><tr><td>C57 Bl/6 Mice</td><td>Jackson Laboratories</td><td></td><td></td></tr><tr><td>Digital Scale and weigh container</td><td>Fisher Scientific</td><td>20031</td><td></td></tr><tr><td>anti-Iba1 antibody</td><td>Wako</td><td>019-19741</td><td></td></tr><tr><td>HRP labelled secondary&amp;nbsp;</td><td>Jackson Immunoresearch</td><td>111-035-003</td><td></td></tr></tbody></table>

a mouse model of single and repetitive mild traumatic brain injury

轻度创伤性脑损伤（mTBI）可导致脑功能急性丧失，包括混乱期，意识丧失（LOC），局部神经功能缺损甚至健忘症。参加联系运动的运动员面临着大量mTBI的高风险。在体育运动员的伤害程度方面，mTBI被定义为不会引起严重病理改变的轻度损伤，但是会导致自发解决的短期神经功能缺损。尽管以前曾尝试在小鼠和老鼠中建模mTBI，但许多人报告了总体不良反应，包括颅骨骨折，脑内出血，轴突损伤和神经元细胞死亡。在这里，我们描述了我们高度重复性的mTBI动物模型，其复制临床相关症状。该型号使用定制的气动冲击器装置来传递闭合头部的创伤。这种影响是在精确的速度和变形参数下进行的，创建一个可靠和可重复的模型来检查有助于单个或重复的震荡mTBI的影响的机制。

使用这种新颖的mTBI装置允许单次和重复的轻度头部损伤，没有颅骨骨折或结构性脑损伤的风险。该型号采用定制的气动特氟龙冲击器装置，可提供封闭的头部机械能量冲击。在精确的速度和变形参数下产生影响，创建可靠和可重复的模型来检查有助于单个或重复的震荡mTBI的影响的机制（ 图1 ）。 LOC的?...

Watch this Scientific Journal Video about A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury at JoVE.com

A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

运动员每年吸收数百次轻度创伤性脑损伤（mTBI）/脑震荡;然而，这些对大脑的后果不甚了解。因此，单次和重复性mTBI的动物模型始终如一地复制临床相关症状，为进一步研究mTBI和脑震荡提供了手段。

单一和重复轻度创伤性脑损伤的小鼠模型

Mild Traumatic Brain Injury (mTBI) can result in the acute loss of brain function, including a period of confusion, a loss of consciousness (LOC), focal ...

a-mouse-model-of-single-and-repetitive-mild-traumatic-brain-injury

Research

JoVE Journal

Medicine

11.1K 次观看.  Georgetown University Medical Center. 运动员每年吸收数百次轻度创伤性脑损伤（mTBI）/脑震荡;然而，这些对大脑的后果不甚了解。因此，单次和重复性mTBI的动物模型始终如一地复制临床相关症状，为进一步研究mTBI和脑震荡提供了手段。 

视频: A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

Inducing Post-Traumatic Epilepsy in a Mouse Model of Repetitive Diffuse Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of acquired epilepsy. TBI can result in a focal or diffuse brain injury. Focal injury is a result of direct mechanical forces, sometimes penetrating through the cranium, creating a direct lesion in the brain tissue. These are visible during brain imaging as areas with contusion, laceration, and hemorrhage. Focal lesions induce neuronal death and glial scar formation and are present in 20%&minus;25% of all people who incur a TBI. However, in the majority of TBI cases, injury is caused by acceleration-deceleration forces and subsequent tissue shearing, resulting in nonfocal, diffuse damage. A subpopulation of TBI patients continues to develop post-traumatic epilepsy (PTE) after a latency period of months or years. Currently, it is impossible to predict which patients will develop PTE, and seizures in PTE patients are challenging to control, necessitating further research. Until recently, the field was limited to only two animal/rodent models with validated spontaneous post-traumatic seizures, both presenting with large focal lesions with massive tissue loss in the cortex and sometimes subcortical structures. In contrast to these approaches, it was determined that diffuse TBI induced using a modified weight drop model is sufficient to initiate development of spontaneous convulsive and non-convulsive seizures, even in the absence of focal lesions or tissue loss. Similar to human patients with acquired post-traumatic epilepsy, this model presents with a latency period after injury before seizure onset. In this protocol, the community will be provided with a new model of post-traumatic epilepsy, detailing how to induce diffuse non-lesional TBI followed by continuous long-term video-electroencephalographic animal monitoring over the course of several months. This protocol will detail animal handling, the weight drop procedure, the electrode placement for two acquisition systems, and the frequent challenges encountered during each of the steps of surgery, postoperative monitoring, and data acquisition.

This systematic protocol describes a new animal model of post-traumatic epilepsy after repetitive mild traumatic brain injury. The first part details steps for traumatic brain injury induction using a modified weight drop model. The second part provides instructions on the surgical approach for single- and multi-channel electroencephalographic data acquisition systems.

在重复性扩散创伤性脑损伤小鼠模型中诱导创伤后癫痫

Traumatic brain injury (TBI) is a leading cause of acquired epilepsy. TBI can result in a focal or diffuse brain injury. Focal injury is a result of ...

科研

行为学

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls, a reliable animal model of mTBI had previously not been developed for this important aspect of development. The modified weight-drop technique employs a glancing impact to the head of a freely moving rodent transmitting acceleration, deceleration, and rotational forces upon the brain. When applied to juvenile rats, this modified weight-drop technique induced clinically relevant behavioural outcomes that were representative of post-concussion symptomology. The technique is a rapidly applied procedure with an extremely low mortality rate, rendering it ideal for high-throughput studies of therapeutics. In addition, because the procedure involves a mild injury to a closed head, it can easily be used for studies of repetitive brain injury. Owing to the simplistic nature of this technique, and the clinically relevant biomechanics of the injury pathophysiology, the modified weight-drop technique provides researchers with a reliable model of mTBI that can be used in a wide variety of behavioural, molecular, and genetic studies.

The modified weight-drop technique is an easy, cost-effective procedure used for the induction of mild traumatic brain injury in juvenile rats. This novel technique produces clinically relevant symptomology that will advance the study of mild traumatic brain injury (mTBI) and concussion.

轻度脑外伤的幼年大鼠一种新模式

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor ...

医学

A Repetitive Concussive Head Injury Model in Mice

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of knowledge on the injury and its effects. To develop a better understanding of concussions, animals are often used because they provide a controlled, rigorous, and efficient model. Studies have adapted traditional animal models to perform mTBI to stimulate mild injury severity by changing the injury parameters. These models have been used because they can produce morphologically similar brain injuries to the clinical condition and provide a spectrum of injury severities. However, they are limited in their ability to present the identical features of injuries in patients. Using a traditional impact system, a repetitive concussive injury (rCHI) model can induce mild to moderate human-like concussion. The injury degree can be determined by measuring the period of loss of consciousness (LOC) with a sign of a transient termination of breathing. The rCHI model is beneficial to use for its accuracy and simplicity in determining mTBI effects and potential treatments.

Concussion presents the most common type of traumatic brain injury. Therefore, a repetitive concussive animal model, which replicates the important features of an injury in patients, may provide a means to study concussion in a rigorous, controlled, and efficient manner.

重复震荡颅脑损伤模型小鼠

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of ...

Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the United States. In fact, TBI is a contributing factor to over a third of all injury-related mortality. Nonetheless, the cellular and molecular mechanisms underlying the pathophysiology of TBI are poorly understood. Thus, preclinical models of TBI capable of replicating the injury mechanisms pertinent to TBI in human patients are a critical research need. The controlled cortical impact (CCI) model of TBI utilizes a mechanical device to directly impact the exposed cortex. While no model can full recapitulate the disparate injury patterns and heterogeneous nature of TBI in human patients, CCI is capable of inducing a wide range of clinically applicable TBI. Furthermore, CCI is easily standardized allowing investigators to compare results across experiments as well as across investigative groups. The following protocol is a detailed description of applying a severe CCI with a commercially available impacting device in a murine model of TBI.

Here we describe a protocol for the induction of murine traumatic brain injury via an open-head controlled cortical impact.

创伤性脑损伤诱导受控皮质冲击的母模型

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the ...

神经科学

Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and understanding the mechanisms of how a TBI alters brain function. The availability of multiple animal models of TBI is necessary to model the different aspects and severities of TBI seen in people. This manuscript describes the use of a midline closed head injury (CHI) to develop a mouse model of mild TBI. The model is considered mild because it does not produce structural brain lesions based on neuroimaging or gross neuronal loss. However, a single impact creates enough pathology that cognitive impairment is measurable at least 1 month after injury. A step-by-step protocol to induce a CHI in mice using a stereotaxically guided electromagnetic impactor is defined in the paper. The benefits of the mild midline CHI model include the reproducibility of the injury-induced changes with low mortality. The model has been temporally characterized up to 1 year after the injury for neuroimaging, neurochemical, neuropathological, and behavioral changes. The model is complementary to open skull models of controlled cortical impact using the same impactor device. Thus, labs can model both mild diffuse TBI and focal moderate-to-severe TBI with the same impactor.

The protocol describes mild traumatic brain injury in a mouse model. In particular, a step-by-step protocol to induce a mild midline closed head injury and the characterization of the animal model is fully explained.

小鼠轻度创伤性脑损伤的电磁控制闭头模型

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and ...

在 mTBI 大鼠模型中验证损伤反应和行为评估

Rat Model of Closed-Head Mild Traumatic Injury and its Validation

Animal models are crucial for advancing our understanding of mild traumatic brain injury (mTBI) and guiding clinical research. To achieve meaningful insights, developing a stable and reproducible animal model is essential. In this study, we report a detailed description of a closed-head mTBI model and a representative validation method using Sprague-Dawley rats to verify the modeling effect. The model involves dropping a 550 g mass weight from a height of 100 cm directly onto the head of a rat on a destructible surface, followed by a 180-degree turn. To assess the injury, rats underwent a series of neurobehavioral assessments 10 min post-injury, including time of loss of consciousness, first seeking-behavior time, escape ability, and beam balance ability test. During the acute and subacute stages following the injury, behavioral tests were conducted to assess motor coordination ability (Beam task), anxiety (Open Field test), and learning and memory abilities (Morris Water Maze test). The closed-head mTBI model produced a consistent injury response with minimal mortality and replicated real-life situations. The validation method effectively verified the model development and ensured the stability and consistency of the model.

作者聚焦:推进创伤性脑损伤研究 - 用于准确复制和快速评估的闭头模型 

Here, we present a closed-head mild traumatic brain injury (mTBI) rat model and its validation exhibiting remarkable similarity to human mTBI concerning behavioral manifestations during the acute and subacute stages.

闭合头轻度创伤大鼠模型及其验证

Animal models are crucial for advancing our understanding of mild traumatic brain injury (mTBI) and guiding clinical research. To achieve meaningful ...

通过闭合头部损伤法在小鼠中诱导 rmTBI

Modified Mouse Model of Repetitive Mild Traumatic Brain Injury Incorporating Thinned-Skull Window and Fluid Percussion

Mild traumatic brain injury is a clinically highly heterogeneous neurological disorder. Highly reproducible traumatic brain injury (TBI) animal models with well-defined pathologies are urgently needed for studying the mechanisms of neuropathology after mild TBI and testing therapeutics. Replicating the entire sequelae of TBI in animal models has proven to be a challenge. Therefore, the availability of multiple animal models of TBI is necessary to account for the diverse aspects and severities seen in TBI patients. CHI is one of the most common methods for fabricating rodent models of rmTBI. However, this method is susceptible to many factors, including the impact method used, the thickness and shape of the skull bone, animal apnea, and the type of head support and immobilization utilized. The aim of this protocol is to demonstrate a combination of the thinned-skull window and fluid percussion injury (FPI) methods to produce a precise mouse model of CHI-associated rmTBI. The primary objective of this protocol is to minimize factors that could impact the accuracy and consistency of CHI and FPI modeling, including skull bone thickness, shape, and head support. By utilizing a thinned-skull window method, potential inflammation due to craniotomy and FPI is minimized, resulting in an improved mouse model that replicates the clinical features observed in patients with mild TBI. Results from behavior and histological analysis using hematoxylin and eosin (HE) staining suggest that rmTBI can lead to a cumulative injury that produces changes in both behavior and gross morphology of the brain. Overall, the modified CHI-associated rmTBI presents a useful tool for researchers to explore the underlying mechanisms that contribute to focal and diffuse pathophysiological changes in rmTBI.

作者聚焦：优化啮齿动物模型以研究反复轻度创伤性脑损伤的机制和康复

This protocol presents a modified mouse model of repetitive mild traumatic brain injury (rmTBI) induced via a closed-head injury (CHI) method. The approach features a thinned-skull window and fluid percussion to reduce the inflammation commonly caused by meninges exposure, along with improved reproducibility and accuracy in modeling rmTBI in rodents.

结合颅骨窗变薄和液体叩击的重复性轻度创伤性脑损伤改良小鼠模型

Mild traumatic brain injury is a clinically highly heterogeneous neurological disorder. Highly reproducible traumatic brain injury (TBI) animal models ...

单一和重复轻度创伤性脑损伤的小鼠模型

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