Name: a novel model of mild traumatic brain injury for juvenile rats
Uploaded: 2014-12-08T13:00:00.000+00:00
Duration: 7 min 36 s
Description: Watch this Scientific Journal Video about A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats at JoVE.com

The authors would like to thank Irene Ma, Rose Tobais, and Jong Rho for their technical assistance. Funding was provided to MJE by the Department of Pediatrics at the University of Calgary, the Alberta Children&#8217;s Hospital Foundation (ACHF) and the Alberta Children&#8217;s Hospital Research Institute (ACHRI). The Postdoctoral fellowship for RM was provided by ACHF.

注:所有实验，进行了符合动物护理的加拿大议会和批准了卡尔加里大学，动物保健伦理委员会。 1.育种和动物准备<ol><li>按照标准养殖协议，订购孕鼠从内部标准实验动物供应商或品种的幼崽。 </li><li>房子所有动物随意获得食物和水，在温度受控的大鼠容纳室（21℃），即保持在12:12小时的光:暗周期。 </li><li>当幼崽出生后达到21天（P21），断奶同性群体的3或4，从他们的母亲和幼仔的房子。 </li></ol> 2.建立轻度脑外伤（MTBI）的设备<ol><li>此前毕业典礼程序，重磨到所需的质量（ 如 150克）。牢固地附着在金属环的重量的顶端使渔线被连接固定的，以重量。 </li><li>得分锡箔用锋利的剃刀刀片。确保打进锡箔支撑体重的大鼠的但与鼠的加速度在与重量头部冲击不会干涉。 </li><li>磁带上的计分锡箔到U形平台由透明塑料（38×27×27 毫升 ），其中包含一个集合海绵（38×25×15cm的3）（ 图1），以便它是绷紧。 </li><li>将U形的塑料阶段在导向管由透明塑料下的正确位置。 </li><li>持在塑料导向管（2.2厘米直径的乘以1.5米）代替用夹子支架和导向管的位置，以便它为3.5厘米以上的计分锡箔。 </li><li>通过金属环连接的钓线确保了重量的底部自由悬挂2.5厘米上面拿下锡箔的重量。 </li><li>牢固地安装鱼线的固定支架。 注意:系链的重量的蛤P支架以2.5厘米以上的锡箔高度防止重新命中，而大鼠是从冲击到集合海绵）落下。 </li><li>通过塑料导管与鱼线拉起来的重量拿在地方与六角扳手销1.0米</li></ol> 3.感应MTBI的<ol><li>当老鼠到达P30招进笼子里的程序空间。 </li><li>放置大鼠在异氟醚的腔室并轻轻麻醉大鼠，直到它是非响应于一个爪子或尾巴捏。 </li><li>赶紧把老鼠的得分锡箔在落锤的路径胸部朝下直接发挥得淋漓尽致。参见图2，如果老鼠开始移动或唤醒之前可放置在打进锡箔，返回到异氟烷室，直到非响应于一个爪子或尾巴捏和再次开始。 </li><li>拉六角扳手引脚，允许重量垂直落下通过塑料导管和罢工老鼠的头部。日Ë老鼠会很快接受一个180°旋转和土地在仰卧位。 </li><li>立即删除从集合海绵大鼠和应用利多卡因于老鼠的头部用棉签。 </li><li>将鼠在由经市售加热垫设置它加热在干净笼子仰卧位。 </li><li>用秒表和数字计时器获得"时间到右"。时间到右是采取的大鼠从麻醉醒来并从仰卧位翻转到俯卧姿势或开始行走的时间。 </li><li>返回老鼠的家笼后，已恢复正常的行为（美容，散步，游览等 ）。 </li><li>每增加大鼠需要MTBI重复步骤3.2-3.8。 </li><li>重复在同一大鼠的程序，在重复性实验MTBI多个时间点。 </li></ol> 4.感应深水损伤<ol><li>轻轻ANESThetize用异氟烷将大鼠直到它是非响应于一个爪子或尾巴捏。 </li><li>赶紧把老鼠的得分锡箔在落锤的路径胸部朝下直接发挥得淋漓尽致。 </li><li>取下锡箔的老鼠没有从塑料导管拉六角扳手引脚和应用外用利多卡因的大鼠头部用棉签。 </li><li>将鼠在由经市售加热垫设置它加热在干净笼子仰卧位。 </li><li>使用秒表或数字计时器来获取"时间到右"。 </li><li>返回老鼠的家笼后，已恢复正常的行为（美容，散步，游览等 ）。 </li></ol> 5.验证MTBI与梁步行测试8 <ol><li>感应的MTBI或假伤愈复出动物的过程房间后24小时。 </li><li>转移大鼠到一个干净的保持笼并放置老鼠的家笼在的165厘米锥形光束，使得家笼的开放端部面向所述光束的较窄端的较窄端。 注:锥形束为165厘米长。光束的中心平台具有6厘米在广角端和1.75厘米的窄端的宽度。该中心梁具有壁架（2厘米，宽2厘米中心束以下），提供安全，当老鼠的脚打滑。放置光束下面泡沫填充以减少鼠可能在测试期间脱落光束伤害的风险。 </li><li>放置一个摄像机在锥形光束和位置的宽端/变焦摄像机以确保研究者观看录像可以清楚地看到的大鼠的运动为锥形束的整个长度。 </li><li>将大鼠在锥形束的广角端，并鼓励其跨梁步行到其家笼。一旦老鼠穿过锥形束，让大鼠在其家笼至少60秒川NFORCE目标位置。这是试验＃1和不包括在分析中。 </li><li>打开视频摄像头，并允许大鼠完成梁行走任务，4个额外的时间（保持在家里笼60秒加固周期）。一旦老鼠已经完成了所有的试验，返回老鼠的家笼。 </li><li>得分，记录后肢脚打滑发生的时间/持续时间越过横梁，为每个单独的试验的次数。使用此数据来计算的后腿英尺单和时间的平均数量越过横梁每只大鼠。 </li></ol>

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No competing financial interests exist.

Reliable modelling systems are needed to effectively cultivate basic science research that has significant translational validity. In response to rising occurrences and popular media, the investigation of mTBI and concussion has become a priority in many disciplines. However, despite increased research, there have been only incremental improvements in therapeutic strategies and treatment options 3. This lack of progress may be partially due to a discrepancy between the modeling systems employed and actual injury etiology. The majority of studies utilized rodent models that failed to reproduce the important biomechanical forces and appropriate post-injury symptomology. The current human definition of mTBI specifies that the injury results from acceleration and deceleration forces associated with a blunt trauma 10. The modified weight drop technique described here is therefore an ideal model for the study of mTBI and concussion because it uses a glancing impact to cause rapid rotational acceleration and deceleration to the head of an unrestrained animal, mimicking the biomechanical forces identified in sports-related injuries and automobile accidents. In addition, this model is easily adapted to examine repetitive mTBI, a phenomena that is emerging as a serious medical and socioeconomic issue. Studies indicate that rodents may be exposed to a series of 10 distinct mTBIs with minimal mortality 7. Finally, the method is inexpensive and can be carried out rapidly, allowing for high-throughput examination of a many therapeutic compounds and treatment regiments. 
Just as with any procedural technique, certain aspects of the protocol are particularly important to the generation of reliable results. First, the tin foil needs to be scored effectively. If the tin foil is not properly scored, the force imparted by the weight during the glancing impact will not be enough to propel the juvenile rat through the tin foil onto the collection sponge. In these situations, the rat will remain in the starting position (chest down on the tin foil) and the mTBI will result from the blunt trauma from the weight impacting the stationary head, not the rotational acceleration and deceleration desired. Second, during the induction of the mTBI and the sham injury, the level of anesthetic applied to each rat should be consistent. Owing to the fact that time-to-right is used as marker of mTBI, the researcher should try to ensure that animals receiving a mTBI and animals receiving a sham injury are exposed to similar levels of anesthetic. A major advantage to this technique over many other TBI procedures is the low level and duration of anesthesiology. However, the juvenile rat needs to be non-responsive to a toe or tail pinch to ensure they do not wake-up on the stage before the injury is induced. Finally, in order to maintain a consistent injury etiology, the positioning of the rat&#8217;s head is particularly important. Ideally the weight should impact the center of the dorsal surface of the head. Caution should be taken to avoid positioning the path of the weight too near the caudal/posterior portion of the head, as impacting the brainstem and cerebellum is associated with increased mortality and seizure activity. 
Based upon the biomechanical pathophysiology of injury induction and the behavioural outcomes examined, the modified weight-drop technique appears to be a reliable model for the investigation of paediatric mTBI and concussion. Although preliminary studies of this novel model have assessed some basic molecular and structural changes 7 future studies will be needed to ascertain how the brain responds to a mTBI with this injury etiology. An in-depth analysis of the neuroanatomical and biological changes that occur at the cellular and epigenetic level would increase model validity and translational applicability. In addition to stimulating the generation of targeted pharmacological therapies, understanding the pathophysiological changes that occur in the brain in response to mTBI and concussion would also direct the research related to clinical biomarkers that have the ability to predict outcomes following injury.

虽然有许多广泛使用的方法的中度至重度创伤性脑损伤（TBI），极少数技术已被开发以诱导温和的生成，关闭头部受伤在啮齿类动物。由于这样的事实，轻度创伤性脑损伤（MTBI）比中度和重度脑损伤合并1三次多见，MTBI的可靠模型，需要以促进关于研究生理学，神经生物学和行为结果，和治疗策略。例如，部分由于当前的动物模型2的局限性，在过去十年中已经有超过200个失败的临床药物试验用于TBI 3的治疗。当转化研究研究，产生模拟系统，对调查结果的适用性取决于实施该模型的有效性。对于MTBI /脑震荡的研究中，一个可靠的动物模型不仅模仿生物力学力量​​responsible对于损伤的病因，而且还会引起与报告的临床相关人口一致的症状。此外，由于儿童处于特别高风险MTBI，优化建模系统将适用于广大青少年啮齿动物，除了成年当量。 ，其中运动员有持续mTBIs震荡或脑损伤的情况下，生物力学分析表明，最关键的预测因子的伤害是快速的头加速和高速冲击4。大部分目前用于TBI诱导啮齿类动物模型的允许头5（综述参见2）很少或没有移动。这里列出的模式，提供了高速冲击物理潇洒的少年大鼠是伴随着一个180°旋转和自由落体适用加速/减速力被摄对象的头部和身体的头。牛逼这里有与MTBI的诱导本变形重量滴技术相关联的两个主要优点。首先，模型产生临床相关的震荡一样症候，而不会造成任何明显的损害到大脑（完整描述行为结果见6）。与后震荡综合征的临床报告也一致，此修改重锤落下技术生产异构的结果。虽然从MTBI的效果是显著，存在经历了MTBI上的多个结果的措施检查当啮齿动物之间大幅变化。其次，该方法允许重复MTBI 7的研究。由于大多数现有的TBI模型造成如此严重的伤害，这是常常难以诱导的第二损伤，并且几乎不可能研究重复TBI而不对整个皮质广泛损害。 因此，对于使用改性重量滴法对工业家里的主要理由MTBI的ction是产生伤害更紧密地代表了青少年群体的病理生理和脑震荡的症状学和重复TBI。随着MTBI的发病率越来越高，涉及到体育，坠落，交通事故，特别是在儿童时期，MTBI这种独特的啮齿动物模型为研究人员提供了震荡式的脑损伤，可以很容易地应用到多个命中研究的宝贵工具范式。

<table><tbody><tr><td>Brass Weights</td><td>Ginsberg Scientific</td><td>7-2500-2</td><td>Need to have metal loop attached to base</td></tr><tr><td>Alluminum Foil</td><td>Alcan</td><td></td><td>Available at most grocery stores</td></tr><tr><td>Masking Tape</td><td></td><td></td><td>Commercially available&amp;nbsp;</td></tr><tr><td>U-Shaped Plastic Stand</td><td></td><td></td><td>Constructed by Laboratory</td></tr><tr><td>Clamp Stand</td><td>Sigma-Aldrich</td><td>Z190357</td><td></td></tr><tr><td>Plastic Guide Tube</td><td></td><td></td><td>Could be constructed or purchased at a hardware store</td></tr><tr><td>Fishing Line</td><td>Angler 10lb&amp;nbsp;</td><td></td><td>Purchased from a sporting goods retailer&amp;nbsp;</td></tr><tr><td>Isoflurane</td><td>Pharmaceutical Partners of Canada</td><td>DIN 02237518</td><td>Inhalation Anesthetic</td></tr><tr><td>Topical Lidocaine (30ml)</td><td>Astra Zeneca</td><td>DIN 0001694</td><td>Xylocaine Jelly 2%&amp;nbsp;</td></tr><tr><td>Cotton Swabs</td><td></td><td></td><td>Commercially available&amp;nbsp;</td></tr><tr><td>Heating Pad - 3 heat setting</td><td></td><td></td><td>Commercially available&amp;nbsp;</td></tr><tr><td>Stop Watch</td><td>Sportline</td><td>L303</td><td>Purchased from a sporting goods retailer&amp;nbsp;</td></tr><tr><td>Video Camera</td><td>Sony</td><td>HDR-CX260V</td><td></td></tr><tr><td>Sprague Dawley Rats</td><td>Charles River Laboratories</td><td>SAS SD 40</td><td>Male and females ordered from Charles River Laboratories and pups bred in-house</td></tr><tr><td>Balance Beam</td><td></td><td></td><td>Constructed by Laboratory</td></tr></tbody></table>

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.

上述改性重锤落下技术对于轻度创伤性脑损伤（MTBI）在幼年大鼠中诱导的可靠方法。利用150克重量的影响，该技术已成功应用于范围从50-120克幼年大鼠。此外，该程序可以很容易地反复在同一动物重复MTBI的研究。虽然醒来后的动物，经历一个单一MTBI展览增加了时间-右（ 图3）和出现愣，它们迅速地恢复正常的活动，并从假损伤动物视觉上没有区别。鉴于该损伤是温和的，局部的利多卡因这消除了与掠冲击相关联的任何疼痛，需要唯一的止痛剂。这是研究的重要的止痛药是已知的干扰典型的炎症和恢复过程。由于缺乏明显的症状学的，光束行走任务是一个可靠的，以醇可用于验证MTBI的诱导。需要注意的是，并非所有的动物，体验MTBI将展示在梁行走任务赤字是很重要的，但作为一个群体，少年只用MTBI展示显著更多的后腿脚打滑时相比，幼年大鼠假伤（ 图4）。 这个修改​​重锤落下技术的另一个重要特点是在伤害感应应用到青少年老鼠缺乏约束。通过提供一个一眼打击头部后迅速旋转加速，减速，这种模式更加紧密地代表归因于MTBI和脑震荡的生物力学的力量。在此过程中被应用到幼年大鼠或成年小鼠，死亡率极低（二百零二分之七幼年动物〜3.4％的死亡率），以及颅骨骨折和颅内出血是非常罕见6,7。此外，该模型会产生临床相关SYmptomology。在经历一个MTBI少年老鼠表现出平衡和运动行为缺陷，随着赤字的行政职能，提高抑郁样行为，并改变了社会交往6,9。同样，成年小鼠还显示，随着时间的7轻度恢复平衡和协调赤字。最后，使用感应MTBI这种模式的需要最少的麻醉，不涉及手术准备，​​或钻入头骨。结果，因此不通过由手术或麻醉触发混杂炎性或免疫效应偏置。此外，开放性伤口的快速恢复时间和缺乏使更多的测试范例开始出现老鼠体验MTBI后不久。 <img alt="图1" fo:content-width="5in" src="/files/ftp_upload/51820/51820fig1highres.jpg" width="500" /> 图1: </strong<html> &gt; 的U形塑料阶段，收集海绵与所有相关方面。必须保持在收集海绵和塑料的阶段，以确保青少年老鼠顶部之间的10厘米的距离C artoon代表有足够的时间来完成180 °旋转。 <img alt="图2" fo:content-width="5in" src="/files/ftp_upload/51820/51820fig2highres.jpg" width="500" /> 图2:伤害感应平台（A）摄影代表性。少年大鼠放置在打进锡箔胸部向下，使得头部直接落锤下方。损伤感应平台（B）的侧视图。（C）的 MTBI的诱导中使用的重量的照相示范。 上传/ 51820 / 51820fig3highres.jpg"WIDTH ="500"/&gt; 图3:那经历了一个MTBI并经历了假伤害幼鼠（* P &lt;0.01），老鼠收到了MTBI展览在一个显著增加时间到右幼年大鼠之间的平均差异的图形表示的持续时间需要从仰卧位纠正自己。 <img alt="图4" fo:content-width="5in" src="/files/ftp_upload/51820/51820fig4highres.jpg" width="500" /> 图4:后腿足单由幼年大鼠表现出的光束行走的任务，经历了一个MTBI并经历了假伤害幼鼠（* P &lt;0.05）的平均数量的图形表示。

Watch this Scientific Journal Video about A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats at JoVE.com

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

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-novel-model-of-mild-traumatic-brain-injury-for-juvenile-rats

Nanyang Technological University

Research

JoVE Journal

Medicine

23.5K 次观看.  University of Calgary. 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. 

视频: A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, few studies have investigated the long-term effects of injury in rodent models of TBI. Shown here are behavioral measures that are well-established in TBI research for times early after injury, such as two weeks, until two months. Some of these methods have previously been used at later times after injury, up to one year, but by very few laboratories. The methods demonstrated here are a short neurological assessment to test reflexes, a Beam-Balance to test balance, a Beam-Walk to test balance and motor coordination, and a working memory version of the Morris water maze that can be sensitive to deficits in reference memory. Male rats were handled and pre-trained to neurological, balance, and motor coordination tests prior to receiving parasagittal fluid percussion injury (FPI) or sham injury. Rats can be tested on the short neurological assessment (neuroscore), the beam-balance, and the Beam-Walk multiple times, while testing on the water maze can only be done once. This difference is because rats can remember the task, thus confounding the results if repeated testing is attempted in the same animal. When testing from one to three days after injury, significant differences are detected in all three non-cognitive tasks. However, differences in the Beam-Walk task were not detectable at later time points (after 3 months). Deficits were detected at 3 months in the Beam-Balance and at 6 months in the neuroscore. Deficits in working memory were detected out to 12 months after injury, and a deficit in a reference memory first appeared at 12 months. Thus, standard behavioral tests can be useful measures of persistent behavioral deficits after FPI.

The goal of the behavioral tests presented here is to detect functional deficits in rats after traumatic brain injury. Four specific tests are presented that detect deficits in behaviors to reflect the damage to specific brain areas at times extending to one year after injury.

颅脑损伤后大鼠行为缺陷的检测

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, ...

科研

行为学

Assessing Dominant-Submissive Behavior in Adult Rats Following Traumatic Brain Injury

Competition over resources such as food, territory, and mates significantly influences relationships within animal species and is mediated through social hierarchies that are often based on dominant-submissive relationships. The dominant-submissive relationship is a normal behavioral pattern among the individuals of a species. Traumatic brain injury is a frequent cause of social interaction impairment and the reorganization of dominant-submissive relationships in animal pairs. This protocol describes submissive behavior in adult male Sprague-Dawley rats after the induction of traumatic brain injury using a fluid-percussion model compared to naive rats through a series of dominant-submissive tests performed between 29 days and 33 days after induction. The dominant-submissive behavior test shows how brain injury can induce submissive behavior in animals competing for food. After traumatic brain injury, the rodents were more submissive, as indicated by them spending less time at the feeder and being less likely to arrive first at the trough compared to the control animals. According to this protocol, submissive behavior develops after traumatic brain injury in adult male rats.

The present protocol describes a rat model of fluid percussion-induced traumatic brain injury followed by a series of behavioral tests to understand the development of dominant and submissive behavior. Using this model of traumatic brain injury in conjunction with specific behavioral tests enables the study of social impairments following brain injury.

评估创伤性脑损伤后成年大鼠的显性顺从行为

Competition over resources such as food, territory, and mates significantly influences relationships within animal species and is mediated through social ...

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 ...

医学

A Novel and Translational Rat Model of Concussion Combining Force and Rotation with In Vivo Cerebral Microdialysis

Persistent cognitive and motor symptoms are known consequences of concussions/mild traumatic brain injury (mTBIs) that can be partly attributable to altered neurotransmission. Indeed, cerebral microdialysis studies in rodents have demonstrated an excessive extracellular glutamate release in the hippocampus within the first 10 min following trauma. Microdialysis offers the clear advantage of in vivo neurotransmitter continuous sampling while not having to sacrifice the animal. In addition to the aforementioned technique, a closed head injury model that exerts rapid acceleration and deceleration of the head and torso is needed, as such a factor is not available in many other animal models. The Wayne State weight-drop model mimics this essential component of human craniocerebral trauma, allowing the induction of an impact on the head of an unrestrained rodent with a falling weight. Our novel and translational rat model combines cerebral microdialysis with the Wayne State weight-drop model to study, in lightly anesthetized and unrestrained adult rats, the acute changes in extracellular neurotransmitter levels following concussion. In this protocol, the microdialysis probe was inserted inside the hippocampus as region of interest, and was left inserted in the brain at impact. There is a high density of terminals and receptors in the hippocampus, making it a relevant region to document altered neurotransmission following concussion. When applied to adult Sprague-Dawley rats, our combined model induced increases in hippocampal extracellular glutamate concentrations within the first 10 min, consistent with the previously reported post-concussion symptomology. This combined weight-drop model provides a reliable tool for researchers to study early therapeutic responses to concussions in addition to repetitive brain injury, since this protocol induces a closed-head mild trauma.

Neurotransmitter alteration is a mechanism of neural dysfunction that occurs after concussion and contributes to the sometimes-catastrophic long-term consequences. This rat model combines microdialysis, allowing in vivo neurotransmitter quantification, with a weight-drop technique exerting rapid acceleration and deceleration of the head and torso, an important factor of human craniocerebral trauma.

脑震荡结合力与旋转与Vivo脑微透析的新型和转化大鼠模型

Persistent cognitive and motor symptoms are known consequences of concussions/mild traumatic brain injury (mTBIs) that can be partly attributable to ...

神经科学

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous variability and heterogeneity (age, gender, type of trauma, other possible pathologies, etc.), animal models play a key role in unraveling factors that are limitations in clinical research. They provide a standardized and controlled setting to investigate the biological mechanisms of injury and repair following TBI. However, not all animal models mimic the diffuse and subtle nature of mTBI effectively. For example, the commonly used controlled cortical impact (CCI) and lateral fluid percussion injury (LFPI) models make use of a craniotomy to expose the brain and induce widespread focal trauma, which are not commonly seen in mTBI. Therefore, these experimental models are not valid to mimic mTBI. Thus, an appropriate model should be used to investigate mTBI. The Marmarou weight drop model for rats induces similar microstructural alterations and cognitive impairments as seen in patients who sustain mild trauma; therefore, this model was selected for this protocol. Conventional computed tomography and magnetic resonance imaging (MRI) scans commonly show no damage following a mild injury, because mTBI induces often only subtle and diffuse injuries. With diffusion weighted MRI, it is possible to investigate microstructural properties of brain tissue, which can provide more insight into the microscopic alterations following mild trauma. Therefore, the goal of this study is to obtain quantitative information of a selected region-of-interest (i.e., hippocampus) to follow up disease progression after obtaining a mild and diffuse brain injury.

The overall goal of this procedure is to obtain quantitative microstructural information of the hippocampus in a rat with mild traumatic brain injury. This is done using an advanced diffusion-weighted magnetic resonance imaging protocol and region-of-interest based analysis of parametric diffusion maps.

轻度创伤性脑损伤大鼠海马学的高级扩散成像

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous ...

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 ...

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 ...

轻度脑外伤的幼年大鼠一种新模式

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此视频中的章节

颅脑损伤后大鼠行为缺陷的检测

评估创伤性脑损伤后成年大鼠的显性顺从行为

单一和重复轻度创伤性脑损伤的小鼠模型

脑震荡结合力与旋转与Vivo脑微透析的新型和转化大鼠模型

轻度创伤性脑损伤大鼠海马学的高级扩散成像

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

闭合头轻度创伤大鼠模型及其验证

闭合头轻度创伤大鼠模型及其验证

闭合头轻度创伤大鼠模型及其验证