我们要感谢中南大学实验动物系的所有研究员。本研究得到了国家自然科学基金（第81971791号）的支持;法医学上海市重点实验室， 法医学部重点实验室（法医学研究院）KF202104）。

动物实验由中南大学动物护理和使用委员会批准。所有研究均按照实验动物的福利和伦理原则进行。
1.动物喂养和麻醉程序
<ol><li>群居280-320克Sprague-Dawley雄性大鼠，并将它们维持在12小时/ 12小时的光/暗循环中， 并随意获得食物和水。在大鼠适应环境6天后进行研究。</li>
	<li>在诱导箱中以0.6L / min的气流用3%异氟醚麻醉大鼠，直到它对爪子或尾巴捏没有反应。保持流速30秒。 注意:不使用止痛药，因为它们会干扰大鼠在神经行为评估中的反应。</li>
</ol>2. 术前设置
<ol><li>将硬度值为 35D（海绵重量为 35 kg/m3）的海绵放置在没有顶盖的亚克力盒 （15 cm x 22 cm x 43 cm） 中，长度和宽度相同，但厚度为 12 cm。</li>
	<li>修剪锡箔（厚度为20μm）并使用胶带将其固定在亚克力盒上，以形成能够支撑大鼠重量的可破坏表面。此外，标记一条大约 10 厘米的切割线作为定位大鼠头部的指定位置。</li>
	<li>借助铁架，将 PVC 管牢固地固定到位。准备一个穿孔砝码，重 550 克，直径为 18 毫米。将重物连接到聚氯乙烯或 PVC 管内 1 米高的钓鱼线上。并将导管的位置调整到锡箔上方 3 厘米处。</li>
	<li>准备头盔和枕头。使用直径为 10 毫米、厚度为 3 毫米的不锈钢圆盘制作头盔。准备一个楔形海绵枕头放在老鼠的头部下方，确保它垂直于重力方向。 注: 冲击装置的示意图如 图 1 所示。头盔的作用是识别撞击位置并增强外力的分布。枕头用于保证均匀稳定的损坏。</li>
</ol>3. mTBI诱导
<ol><li>迅速将麻醉的大鼠放在锡箔纸上的胸部。 注意:mTBI 诱导需要两名操作员 - 一名用于准备，另一名用于验证。</li>
	<li>准备:将枕头放在老鼠下面，确保其头部与铝箔纸平行。将头盔与老鼠的耳朵对齐并将其固定到位。</li>
	<li>验证:验证 PVC 管是否位于头盔的正上方。两个操作员确认设置正确后，继续下一步。</li>
	<li>诱导头部旋转:释放重物，让它下落并撞击大鼠的头部，导致跌落到海绵上并旋转 180°。</li>
	<li>将老鼠放在干净的笼子里。</li>
</ol>4. 假诱导
<ol><li>以与先前mTBI诱导描述相同的方式对待大鼠，但不要使其受到头部撞击。</li>
</ol>5. 验证程序:急性神经行为评估
注意:以下评估是根据 Flierl 等人 10 的神经严重程度评分9 和协议修改的。所有这些评估都是在大鼠恢复矫正反射后 10 分钟进行的。
<ol><li>意识丧失时间:记录从大鼠被麻醉到恢复矫正反射的持续时间。 注意:矫正反射是大鼠仰卧时翻身的过程。矫正反射的丧失应被视为人道的终点，并且必须按照机构指南对动物实施安乐死。</li>
	<li>第一次寻找行为时间:记录从大鼠被麻醉到第一次出现寻找行为的持续时间。 注意:寻求行为是对环境感兴趣的标志，是一种生理反应。</li>
	<li>逃生能力<ol><li>将大鼠放在带有出口（长12.5厘米，宽9厘米）的圆形装置（直径0.5米，高0.3米）的中间。</li>
		<li>记录老鼠离开圆圈所需的时间。 注意:如果大鼠在180秒内没有离开圆圈，则将时间记录为180秒。</li>
	</ol></li>
	<li>光束平衡能力测试<ol><li>将大鼠放在3cm，2cm和1.5cm宽的光束上1分钟。</li>
		<li>如果大鼠在横梁上保持平衡，保持稳定姿势，则将其打为 0。</li>
		<li>如果老鼠抓住横梁的一侧，则给 1 分。如果老鼠抱住横梁，一只肢体从横梁上掉下来，则将其打成 2。</li>
		<li>如果老鼠拥抱横梁，两肢从横梁上掉下来或在上面旋转（>60 秒），则将其打成 3。</li>
		<li>如果大鼠试图在横梁上保持平衡但掉下来（> 40 秒），则将其打成 4。</li>
		<li>如果大鼠试图在横梁上保持平衡但掉下来（>20 秒），则将其打成 5。</li>
		<li>如果老鼠没有试图平衡或挂在横梁上并在 20 秒内掉下来，则将其打为 6。 注意:光束平衡测试不需要预试验。</li>
	</ol></li>
</ol>6. 验证程序:神经行为评估
注意:在行为实验之前，连续3天每天处理大鼠2分钟，以尽量减少压力和新奇性干扰。所有行为实验都是通过在实验开始前将动物置于测试环境中 60 分钟来进行的。
<ol><li>运动协调能力（光束任务）<ol><li>实验装置<ol><li>将大鼠放在平衡木的一端（长1.5 m，离地面75厘米）。在另一端放置一个逃生箱（倾斜的床上用品家庭笼子）。</li>
			<li>在横梁下方放置泡沫衬垫，以减轻在测试过程中跌倒时对大鼠造成伤害的潜在风险。</li>
			<li>打开摄像机。</li>
			<li>将检测日安排在受伤后或假治疗后的特定时间点（例如，第 1 天、第 3 天和第 7 天）。</li>
		</ol></li>
		<li>培训阶段（2天）<ol><li>训练大鼠连续 3 次穿过 4 厘米宽的光束，然后在 2 厘米宽的光束上进行两次试验。</li>
			<li>在训练过程中，轻轻地引导老鼠穿过光束，直到它们可以不受干扰地轻松穿过光束。</li>
		</ol></li>
		<li>平衡木实验<ol><li>将大鼠放在2厘米宽的光束上连续5次试验。</li>
			<li>当大鼠的鼻子分别越过起点和终点线时，记录每次试验的开始和结束。</li>
			<li>在实验结束时将大鼠放回笼子。</li>
		</ol></li>
		<li>基线测试<ol><li>在受伤或治疗前进行平衡木实验。</li>
			<li>计算这 5 次连续试验的平均值，以建立每只大鼠的基线。</li>
		</ol></li>
		<li>数据分析<ol><li>使用对实验条件不知情的研究人员的视频分析，分析穿过横梁的时间和后足滑倒的总数。</li>
		</ol></li>
	</ol></li>
	<li>焦虑（开放场测试）<ol><li>实验装置<ol><li>准备空旷的场地，确保它干净，没有任何以前的气味提示。将竞技场分为三个区域:中央内区（33 cm x 33 cm）、中间区（66 cm x 66 cm）和外区。</li>
		</ol></li>
		<li>测试阶段<ol><li>将一只老鼠放在空旷场地的中央并启动计时器。让老鼠自由探索竞技场 5 分钟。5分钟后，小心轻轻地将老鼠放回笼子里。</li>
		</ol></li>
		<li>数据采集<ol><li>测量大鼠在 5 分钟的探索期间行进的总距离。确定大鼠在中央内区、中区和外区停留的时间。</li>
		</ol></li>
		<li>数据分析<ol><li>使用行进的总距离作为整体探索行为和运动能力的衡量标准。计算在中央内区花费的时间，作为焦虑样反应的指标。</li>
		</ol></li>
	</ol></li>
	<li>学习和记忆能力（莫里斯水迷宫测试）<ol><li>确保水迷宫设备处于正常状态。将水染成黑色，并在四个基本方向上放置提示。将平台放置在水面以下 2.5 厘米处。</li>
		<li>设置监控系统来记录和观察老鼠的行为。</li>
		<li>步道日<ol><li>迅速将老鼠放入水迷宫中。如果老鼠未能在2分钟内到达平台，请用木棍轻轻引导它。</li>
			<li>让老鼠在平台上站立 20 秒时熟悉迷宫环境，然后将其移除。一旦老鼠在平台上，让它停留 20 秒，然后将其移除。</li>
		</ol></li>
		<li>每日重复<ol><li>重复训练日程序，将大鼠放入不同象限的水中。重复步骤 6.3.3。连续 5 天继续训练。</li>
		</ol></li>
		<li>探针测试日:在第 6天，取下平台并将大鼠置于同一象限2分钟。</li>
		<li>观察和记录:利用监测系统监测大鼠在试验和探测测试日的行为。</li>
		<li>清洁:将老鼠从水迷宫中取出后，用毛巾彻底擦干。</li>
	</ol></li>
</ol>

在 mTBI 大鼠模型中验证损伤反应和行为评估

<ol>
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作者没有经济利益需要披露。

该模型成功地模拟了闭合的头部 mTBI，而无需头皮切口或颅骨开口，从而更准确地表示了在人类病例中观察到的撞击场景。避免头皮切口有助于防止可能与实际情况不符的炎症反应。与 Richelle Mychasiuk 的儿科模型12 相比，本研究中使用的模型专为体重在 280-320 g 之间的成年大鼠量身定制，使我们能够获得对 mTBI 对成年个体影响的宝贵见解。此外，结合枕头和头盔等关键部件有助于?...

轻度创伤性脑损伤 （mTBI） 或脑震荡是最普遍的损伤类型，可导致各种短期和慢性症状1。这些症状可能包括头晕、头痛、抑郁和快感缺乏等，导致受 mTBI2 影响的个体遭受重大痛苦。由于大多数 mTBI 是由钝器外伤引起的 3，因此必须开发准确模拟此类损伤的动物模型。这些模型对于更好地了解损伤及其潜在机制至关重要，与人类研究相比，提供了一个可控的环境，减少了变异性和异质性。
已经开发了许多成熟的啮齿动物模型来治疗创伤性脑损伤 （TBI），包括液体叩击损伤 （FPI）4、受控皮质冲击 （CCI）5、体重下降损伤6、爆炸性创伤性脑损伤7 等。然而，这些模型主要侧重于复制中度至重度 TBI 情景。相比之下，专门设计用于模拟 mTBI 的实验模型受到的关注相对较少，并且仍未得到充分探索8。因此，迫切需要建立一个稳定且可重复的动物模型，以准确表示mTBI。这样的模型将显着增强我们对与 mTBI 相关的神经生物学和行为后果的理解。
在麻醉效果消失后，人们无法通过随意观察来区分mTBI大鼠与正常大鼠的功能缺陷。因此，有必要进行特定的测试。在人类中，广泛的临床评估用于评估患者 9,10,11。同样，在大鼠模型中建立一个成功的模型也需要使用快速评估工具来确定其有效性。
在这项研究中，我们提出了一个闭头mTBI大鼠模型，能够以与人类状况非常相似的方式研究mTBI。对模型及其验证程序的详细描述提供了对研究 mTBI 所用实验方法的全面理解。

<table><tbody><tr><td>Acrylic box</td><td>In-house</td><td>N/A</td><td>15 cm x 22 cm x 43 cm</td></tr><tr><td>Anesthesia Machine</td><td>RWD Life Science Co.</td><td>R540 Mice &amp;amp; Rat Animal Anesthesia Machine</td><td></td></tr><tr><td>Helmet</td><td>In-house</td><td>N/A</td><td>Stainless-steel disk measuring 10 mm in diameter and 3 mm in thickness</td></tr><tr><td>Morris water maze</td><td>RWD Life Science Co.</td><td></td><td>Diameter 150 cm, height 50 cm,platform diameter 35 cm</td></tr><tr><td>Open field</td><td>RWD Life Science Co.</td><td>63007</td><td>Width100 cm, height 40 cm</td></tr><tr><td>Panlab SMART V3.0</td><td>RWD Life Science Co.</td><td>SMART v3.0</td><td></td></tr><tr><td>Perforated weight</td><td>In-house</td><td>N/A</td><td>Weight of 550 g and diameter of 18 mm</td></tr><tr><td>Pillow</td><td>In-house</td><td>N/A</td><td>Wedge-shaped sponge to place beneath the rat&#039;s head</td></tr></tbody></table>

rat model of closed-head mild traumatic injury and its validation

动物模型对于促进我们对轻度创伤性脑损伤 （mTBI） 的理解和指导临床研究至关重要。为了获得有意义的见解，开发稳定且可重复的动物模型至关重要。在这项研究中，我们报告了闭头 mTBI 模型的详细描述以及使用 Sprague-Dawley 大鼠验证建模效果的代表性验证方法。该模型涉及将 550 克的质量砝码从 100 厘米的高度直接落到可破坏表面上的大鼠头部，然后进行 180 度转弯。为了评估损伤，大鼠在受伤后 10 分钟接受了一系列神经行为评估，包括意识丧失时间、首次寻找行为时间、逃生能力和光束平衡能力测试。在受伤后的急性和亚急性阶段，进行行为测试以评估运动协调能力（光束任务）、焦虑（开放场地测试）以及学习和记忆能力（莫里斯水迷宫测试）。闭头 mTBI 模型以最低的死亡率产生了一致的损伤反应，并复制了现实生活中的情况。验证方法有效地验证了模型的开发，保证了模型的稳定性和一致性。

这项工作中使用的设备是 Kane 模型和 Richelle Mychasiuk 的儿科模型11,12 的改进版本。在这项研究中，SD大鼠被分配到假手术组和mTBI组。为了证明该模型的可重复性，我们对该模型进行了三次独立重复以及急性神经行为评估，每个实验涉及 8-12 只大鼠。在这项研究中，我们使用了 30 多只 mTBI 大鼠，其中 2 只大鼠因麻醉而死亡。然而?...

Watch this Scientific Journal Video about Advancing Traumatic Brain Injury Research — A Closed-Head Model for Accurate Replication and Rapid Assessment at JoVE.com

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 

在这里，我们提出了一个闭合式轻度创伤性脑损伤 （mTBI） 大鼠模型及其验证，在急性和亚急性阶段的行为表现方面与人类 mTBI 表现出显着的相似性。

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 ...

在这项研究中，我们介绍了一个闭头、轻度创伤性脑损伤大鼠模型，并对其验证进行了全面概述。我们的目标是提供一种简单的方法来复制这种类型的脑损伤，并提供一种快速评估方法来确认模型的成功。该模型成功地模拟了闭合的头部、轻度创伤性脑损伤，无需头皮切口或颅骨开口，更准确地表示了在人类病例中观察到的撞击场景。避免头皮切口有助于防止可能与活动情况不一致的炎症反应。轻度创伤性脑损伤缺乏主观和准确的诊断方法。未来，我们的实验室将继续探索可能的生物分子标志物及其深层分子机制，并帮助将获得的分子标记物转化为临床和法医鉴定实践。

rat-model-of-closed-head-mild-traumatic-injury-and-its-validation

Research

JoVE Journal

Neuroscience

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

1.1K 次观看.  School of Basic Medical Science, Central South University. 在这项研究中，我们介绍了一个闭头、轻度创伤性脑损伤大鼠模型，并对其验证进行了全面概述。我们的目标是提供一种简单的方法来复制这种类型的脑损伤，并提供一种快速评估方法来确认模型的成功。该模型成功地模拟了闭合的头部、轻度创伤性脑损伤，无需头皮切口或颅骨开口，更准确地表示了在人类病例中观察到的撞击场景。避免头皮切口有助于防止可能与活?...

视频: 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 

Controlled Cortical Impact Model for Traumatic Brain Injury

Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.

Traumatic brain injuries (TBIs) remain a serious health problem. Using the controlled cortical impact surgery model, research on the effects of TBI and possible treatment methods may be performed.

控制皮层影响模型创伤性脑损伤

Every year over a million Americans suffer a traumatic brain injury (TBI).  Combined with the incidence of TBIs worldwide, the physical, emotional, ...

科研

医学

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 ...

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 ...

A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

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 neurological deficits and even amnesia. Athletes participating in contact sports are at high risk of exposure to large number of mTBIs. In terms of the level of injury in a sporting athlete, a mTBI is defined as a mild injury that does not cause gross pathological changes, but does cause short-term neurological deficits that are spontaneously resolved. Despite previous attempts to model mTBI in mice and rats, many have reported gross adverse effects including skull fractures, intracerebral bleeding, axonal injury and neuronal cell death. Herein, we describe our highly reproducible animal model of mTBI that reproduces clinically relevant symptoms. This model uses a custom made pneumatic impactor device to deliver a closed-head trauma. This impact is made under precise velocity and deformation parameters, creating a reliable and reproducible model to examine the mechanisms that contribute to effects of single or repetitive concussive mTBI.

Athletes absorb several hundred mild traumatic brain injuries (mTBI)/concussions every year; however, the consequence of these on the brain is poorly understood. Therefore, an animal model of single and repetitive mTBI that consistently replicates clinically relevant symptoms provides the means to advance the study of mTBI and concussion.

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 ...

Low-intensity Blast Wave Model for Preclinical Assessment of Closed-head Mild Traumatic Brain Injury in Rodents

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of medical visits in the United States. There are currently no FDA-approved treatments available for TBI. The increased incidence of military-related, blast-induced TBI further accentuates the urgent need for effective TBI treatments. Therefore, new preclinical TBI animal models that recapitulate aspects of human blast-related TBI will greatly advance the research efforts into the neurobiological and pathophysiological processes underlying mild to moderate TBI as well as the development of novel therapeutic strategies for TBI.
Here we present a reliable, reproducible model for the investigation of the molecular, cellular, and behavioral effects of mild to moderate blast-induced TBI. We describe a step-by-step protocol for closed-head, blast-induced mild TBI in rodents using a bench-top setup consisting of a gas-driven shock tube equipped with piezoelectric pressure sensors to ensure consistent test conditions. The benefits of the setup that we have established are its relative low-cost, ease of installation, ease of use and high-throughput capacity. Further advantages of this non-invasive TBI model include the scalability of the blast peak overpressure and the generation of controlled reproducible outcomes. The reproducibility and relevance of this TBI model has been evaluated in a number of downstream applications, including neurobiological, neuropathological, neurophysiological and behavioral analyses, supporting the use of this model for the characterization of processes underlying the etiology of mild to moderate TBI.

We present here a protocol of a blast wave model for rodents to investigate neurobiological and pathophysiological effects of mild to moderate traumatic brain injury. We established a gas-driven, bench-top setup equipped with pressure sensors allowing for reliable and reproducible generation of blast-induced mild to moderate traumatic brain injury.

低强度冲击波模型用于啮齿动物闭头轻度创伤性脑损伤的临床前评估

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of ...

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 ...

Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of closed-head mTBI in the preclinical setting to increase translatability to the clinical population. The awake closed-headed injury (ACHI) model uses a modified controlled cortical impactor to deliver closed-headed injury, inducing clinically relevant behavioral deficits without the need for a craniotomy or the use of an anesthetic.
This technique does not normally induce fatalities, skull fractures, or brain bleeds, and is more consistent with being a mild injury. Indeed, the mild nature of the ACHI procedure makes it ideal for studies investigating repetitive mTBI (r-mTBI). Growing evidence indicates that r-mTBI can result in a cumulative injury that produces behavioral symptoms, neuropathological changes, and neurodegeneration. r-mTBI is common in youths playing sports, and these injuries occur during a period of robust synaptic reorganization and myelination, making the younger population particularly vulnerable to the long-term influences of r-mTBI.
Further, r-mTBI occurs in cases of intimate partner violence, a condition for which there are few objective screening measures. In these experiments, synaptic function was assessed in the hippocampus in juvenile rats that had experienced r-mTBI using the ACHI model. Following the injuries, a tissue slicer was utilized to make hippocampal slices to evaluate bidirectional synaptic plasticity in the hippocampus at either 1 or 7 days following the r-mTBI. Overall, the ACHI model provides researchers with an ecologically valid model to study changes in synaptic plasticity following mTBI and r-mTBI.

Here, it is demonstrated how an awake closed-head injury model can be used for examining the effects of repeated mild traumatic brain injury (r-mTBI) on synaptic plasticity in the hippocampus. The model replicates important features of r-mTBI in patients and is used in conjunction with in vitro electrophysiology.

使用轻度创伤性脑损伤的清醒闭合性头部损伤模型评估突触可塑性的变化

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of ...

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 ...

闭合头轻度创伤大鼠模型及其验证

副本

摘要

探索更多视频

此视频中的章节

控制皮层影响模型创伤性脑损伤

轻度脑外伤的幼年大鼠一种新模式

重复震荡颅脑损伤模型小鼠

单一和重复轻度创伤性脑损伤的小鼠模型

低强度冲击波模型用于啮齿动物闭头轻度创伤性脑损伤的临床前评估

小鼠轻度创伤性脑损伤的电磁控制闭头模型

使用轻度创伤性脑损伤的清醒闭合性头部损伤模型评估突触可塑性的变化

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

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

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