Name: a repetitive concussive head injury model in mice
Uploaded: 2016-10-12T14:00:00.000+00:00
Duration: 5 min 42 s
Description: Watch this Scientific Journal Video about A Repetitive Concussive Head Injury Model in Mice at JoVE.com

This works was supported by funding from a Florida Health grant (Brain and spinal cord injury research fund) (KKW).

根据协议＃201207692由佛罗里达大学的机构动物护理和使用委员会，并按照卫生指南实验动物的护理和使用国家认可的机构进行所有的程序。 1.动物护理<ol><li>使用3-4个月大的雄性C57BL / 6J小鼠。提供床上用品，排料，食品， 自由采食和饮水 。保持小鼠控制在20环境温度 - 22℃，恒定的12小时光照/ 12小时黑暗的周期。 </li></ol> 2.预嵌塞准备<ol><li>安装一个特制的硅橡胶涂层的金属尖的电磁影响立体设备。确保尖端的平底平行于探头尖端（ 图1A）的表面上。 </li><li>麻醉，用4％的异氟醚后2.5％异氟烷维持麻醉的小鼠。检查经由流量计的麻醉。 MonitoR中的麻醉水平，直至达到动物展示踏板撤回反射消失手术水平的麻醉。 </li><li>把鼠标在一个加热垫俯卧。使用一个漏斗形鼻锥保持鼠标麻醉下。使用微调完全剃光头。使用鼠标的眼睛凡士林眼药膏，以防止干燥时的麻醉下。 </li></ol> 3.影响参数设置注:冲击系统包括控制箱设置冲击参数，以执行嵌塞的致动器，并用3-运动轴的数字立体定位框架。 <ol><li>冲击装置的速度预先设定为4米/秒和停留时间，以在控制箱240毫秒。 </li></ol> 4.定位影响中心<ol><li>把动物的身下软加热垫，以保持身体的温度接近39℃。安装鼠标立体定位框架中PRON用钝头耳条E的位置。 </li><li>降低的影响，通过尖端移动Z驱动器靠近鼠标的头部。通过向目标坐标矢状缝上述中途移动所述X和Y驱动调整平面冲击尖端（9毫米直径的）。 </li><li>确保冲击尖端的一个边缘被垂直地平行于两个耳朵（ 图 1C）之间画的假想水平线。冲击的中心对应于interfrontal和人字缝之间的中心矢状缝中途（耳间9毫米到耳间0毫米，横向4.5毫米）。 </li></ol> 5.影响深度设定<ol><li>要正确设置的影响深度，使用额外的探头尖端更换绝缘硅橡胶涂层的影响一角。 </li><li>为了确保有切换提示后无冲击中心的转变，切换提示前，数字立体控制面板上的X和Y通道设置为零。 </li><li>移动概率E喷嘴的冲击区域的中心手动移动X和Y驱动器。 </li><li>夹子接触式传感器鼠标的尾巴。 </li><li>移动至冲击（Z驱动），直到探针尖端接触的冲击部位的表面上。 </li><li>立体定位控制面板上的Z通道设置为零。 </li><li>通过手动调节X轴和Y驱动器（未在数字立体控制面板上的零的按钮），直到X和Y驱动移动至冲击尖端回到冲击面积是零（其中冲击尖端先前定位）。 </li><li>由控制箱移动收缩开关缩回致动器。手动4 mm将撞击向下（Z驱动器）。 </li></ol> 6.影响<ol><li>通过点击在控制箱的冲击开关触发的影响，并实现4mm的变形深度。 </li></ol> 7.后嵌塞<ol><li>直到使用定时器鼠标的第一次呼吸测量从影响的时间。 </li><li&gt;从仪器上取下动物，并将其放置在一个温暖的垫来维持自己的体温。不要离开无人看管的动物，直到它已经恢复了足够的意识，以保持胸骨斜卧。 </li><li>返回动物放回一个干净的笼子前，允许进行恢复。不要动物重返公司其他动物，直到完全康复。 </li><li>观察并每天称重小鼠。如果小鼠显示疼痛的迹象，腹膜内以1美洛昔康注射他们 - 2毫克/公斤，每12 - 24小时。 </li></ol> 8.重复嵌塞<ol><li>给老鼠额外伤害7日4，和10最初的损伤（影响之间72小时间隔）之后。 </li></ol> 9.免疫组织化学（IHC） <ol><li> 穿心灌注 <ol><li>麻醉经由腹膜内注射的小鼠的200米/公斤戊巴比妥。 </li><li>评估并通过脚趾捏保证手术面麻醉。二段URE在仰卧位鼠标的前爪和后爪轻轻的录音，以聚苯乙烯泡沫塑料工作表面化学通风柜内。 </li><li>通过沿着刚刚剑突至锁骨下胸腔中线的皮肤做一个切口。使两个附加的皮肤切口在剑突和沿腹胸腔横向的底部进行。 </li><li>打开胸腔，并通过胸部肌肉和胸腔切割暴露心脏。 </li><li>固定跳动的心脏钝钳，并进行1 - 左心室2毫米切口。 </li><li>立即插入一个蝴蝶针入右心房。通过推动注射器缓慢开始20毫升盐水的输注。 </li><li>从切换到生理盐水4％多聚甲醛。继续与多聚甲醛20ml的灌注。 </li><li>斩首鼠标并用剪刀去除皮肤。使用骨刀头骨隔离大脑。 </li></ol></li><li> Cryostat切片<ol><li>在最佳切削温度（OCT）制定和冻结嵌入脑组织在-80℃。放置在低温恒温器的大脑矢状方向。切脑切片5微米厚。 </li></ol></li><li> 染色 <ol><li>干燥在常温下的冷冻切片1小时。 </li><li>用100μl2％山羊血清和0.1％的Triton X-100的磷酸盐缓冲盐水（PBS），在室温1小时孵育的幻灯片。 </li><li>用300微升PBS洗幻灯片的3倍。在4℃下:（200 1）分别过夜:然后孵育用抗GFAP（1 200）的幻灯片或抗铁蛋白抗体。 </li><li>用300微升PBS洗幻灯片的3倍。然后孵育载玻片在室温下与生物素缀合的二级抗体2小时。 </li><li>用300微升PBS洗幻灯片的3倍。然后孵育与抗生物素蛋白 - 生物素复合物（ABC）溶液（1:50）在室温下30分钟的幻灯片。 </li><li>用300微升PBS洗幻灯片的3倍。 8分钟-然后在3,3&#39;-二氨基联苯胺为5（DAB）底物溶液（50毫升的PBS，10微升的 H 2 O 2，10毫克的DAB丸，在使用前过滤器）孵育。观察载玻片，在显微镜下，直到阳性细胞出现。 </li><li>冲洗在缓慢的流动自来水将载玻片5分钟。干净的玻片用实验室擦拭。然后装入带安装介质和盖玻片的章节。 </li></ol></li></ol>

<ol>
	<li>Baugh, C. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+traumatic+encephalopathy:+neurodegeneration+following+repetitive+concussive+and+subconcussive+brain+trauma.">Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma.</a> Brain Imaging Behav. 6 (2), 244-254 (2012).</li><li>McKee, A. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+traumatic+encephalopathy+in+athletes:+progressive+tauopathy+after+repetitive+head+injury.">Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury.</a> J. Neuropathol Exp Neurol. 68 (7), 709-735 (2009).</li><li>Petraglia, A. L., Dashnaw, M. L., Turner, R. C., Bailes, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Models+of+mild+traumatic+brain+injury:+translation+of+physiological+and+anatomic+injury.">Models of mild traumatic brain injury: translation of physiological and anatomic injury.</a> Neurosurgery. 75 Suppl (4), S34-S49 (2014).</li><li>Goldstein, L. E., McKee, A. C., Stanton, P. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Considerations+for+animal+models+of+blast-related+traumatic+brain+injury+and+chronic+traumatic+encephalopathy.">Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy.</a> Alzheimers Res Ther. 6 (5), 64 (2014).</li><li>Gold, E. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+assessment+of+long-term+deficits+in+rodent+models+of+traumatic+brain+injury.">Functional assessment of long-term deficits in rodent models of traumatic brain injury.</a> RegenMed. 8 (4), 483-516 (2013).</li><li>Xiong, Y., Mahmood, A., Chopp, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+traumatic+brain+injury.">Animal models of traumatic brain injury.</a> Nat Rev Neurosci. 14 (2), 128-142 (2013).</li><li>Luo, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+cognitive+impairments+and+pathological+alterations+in+a+mouse+model+of+repetitive+mild+traumatic+brain+injury.">Long-term cognitive impairments and pathological alterations in a mouse model of repetitive mild traumatic brain injury.</a> Front Neurol. , 5-12 (2014).</li><li>Yang, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Temporal+MRI+characterization,+neurobiochemical+and+neurobehavioral+changes+in+a+mouse+repetitive+concussive+head+injury+model.">Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model.</a> Sci Rep. 10 (5), 11178 (2015).</li><li>Zhang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhibition+of+monoacylglycerol+lipase+prevents+chronic+traumatic+encephalopathy-like+neuropathology+in+a+mouse+model+of+repetitive+mild+closed+head+injury.">Inhibition of monoacylglycerol lipase prevents chronic traumatic encephalopathy-like neuropathology in a mouse model of repetitive mild closed head injury.</a> J Cereb Blood Flow Metab. 35 (3), 443-453 (2015).</li><li>Petraglia, A. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+spectrum+of+neurobehavioral+sequelae+after+repetitive+mild+traumatic+brain+injury:+a+novel+mouse+model+of+chronic+traumatic+encephalopathy.">The spectrum of neurobehavioral sequelae after repetitive mild traumatic brain injury: a novel mouse model of chronic traumatic encephalopathy.</a> J Neurotrauma. 31 (13), 1211-1224 (2014).</li><li>Lumpkins, K. M., Bochicchio, G. V., Keledjian, K., Simard, J. M., McCunn, M., Scalea, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glial+fibrillary+acidic+protein+is+highly+correlated+with+brain+injury.">Glial fibrillary acidic protein is highly correlated with brain injury.</a> J Trauma. 65 (4), 778-782 (2008).</li><li>Yang, Z., Wang, K. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glial+fibrillary+acidic+protein:+from+intermediate+filament+assembly+and+gliosis+to+neurobiomarker.">Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker.</a> Trends Neurosci. 38 (6), 364-374 (2015).</li><li>Liu, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+expression+of+ferritin+in+cerebral+cortex+after+human+traumatic+brain+injury.">Increased expression of ferritin in cerebral cortex after human traumatic brain injury.</a> Neurol Sci. 34 (7), 1173-1180 (2013).</li><li>Jordan, B. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+clinical+spectrum+of+sport-related+traumatic+brain+injury.">The clinical spectrum of sport-related traumatic brain injury.</a> Nat Rev Neurol. 9 (4), 222-230 (2013).</li></ol>

The authors have no financial interest to disclose.

模仿脑损伤形态相似的临床病症，预期脑震荡后症状。脑震荡的症状后一般包括头痛，头晕，眼花，乏力，记忆力和睡眠障碍，注意力无法集中以及焦虑，情绪低落。由于躯体症状可能还不是在动物模型衡量，运动和认知功能和情感行为的变化作为标准，在动物模型中合理评估脑震荡。在先前的报道的研究中，它表明，在rCHI小鼠模型诱导缺陷在空间学习，记忆和焦虑8。更重要的是，在此...

脑震荡，也被称为轻度颅脑损伤（MTBI），是创伤性脑损伤（TBI）的最频繁发生，影响数百万人在美国。震荡可能会非常棘手的诊断并没有为脑震荡没有具体的治疗。有越来越多的认可和一些证据表明，运动损伤，军事打击，以及其他物理引人入胜的追求导致轻微的机械性损伤可能有累积性，慢性神经后果1,2。然而，仍然有关于脑震荡及其影响的认识不足。现行方法限制病理和治疗的人类研究的，因为只有神经评估和成像评估可用于临床诊断。动物模型提供了学习的脑震荡与进一步的诊断和治疗MTBI的希望高效，严谨，可控的方式的一种手段。 有研究适应传统的TBI车型如控制皮质影响（CCI），液压冲击影响（FPI），体重下降损伤，爆炸伤执行MTBI通过改变参数的伤害低刺激伤害的严重性。这些模型，由于其复制脑外伤形态上类似于临床状况的能力是有益的使用;不过，他们也有自己的局限性。由加速度损伤（重量滴）诱导损伤的严重程度常常是高度可变的。轻度CCI的两种结果 - 蛛网膜下腔出血和挫伤焦点 - 不典型的脑震荡的人可比的。 CCI和FPI需要开颅手术，这不是临床相关，而爆伤是曝光3-6期间关于不同的曝光位置和峰值压力测量一个比较有争议的模型，以及可变继发性损伤。一个更新的震荡动物模型可以转化临床前研究的临床settiNG是必要的研究。 在模拟轻度TBI的关键问题是确定实验损伤严重，其中最密切复制在临床受伤。最近，不同的研究小组开发出闭合性颅脑损伤或震荡头部损伤（CHI）模型7-10。 CHI是CCI的不开颅的修改，但它依然采用的是传统的电子磁场影响系统产生头部撞击。阴气可以通过调节参数的影响引起了脑震荡，从轻度到中度。意识（LOC）的损失可立即通过检测呼吸速率或呼吸的瞬时终止的降低的冲击之后观察到。 LOC的期间被用于确定损伤的严重程度。本文包括小鼠重复CHI（rCHI）模型略有改善和更新版本，以及一个详细的一步一步的协议和代表的搜索结果。该rCHI模型研究战略重新确定MTBI效应和潜在的治疗有益的，特别是因为有能够模仿所有的脑震荡引起的病理变化没有个体动物模型。

<table><tbody><tr><td>anesthesia machine</td><td>Eagle Eye Anesthesia, Inc</td><td>Model 150&amp;nbsp;</td><td>anesthesia</td></tr><tr><td>Electromagnetic Impactor</td><td>LeicaBiosystems</td><td>Impact One Stereotaxic Impactor</td><td>perform impaction</td></tr><tr><td>Digital Stereotaxic instrument</td><td>LeicaBiosystems</td><td>39462501</td><td>mount mouse and positioning tips</td></tr><tr><td>Sicilone rubber-coated metal tip</td><td>Precision Tool &amp;amp; Engineering, Gainesvill FL</td><td>custom-made</td><td>impact tip</td></tr><tr><td>Lithium Ion All-in-One Trimmer</td><td>WAHL Home Products</td><td>9854-600</td><td>shave mouse hair</td></tr><tr><td>paper clips</td><td>custom-made</td><td></td><td>probe tip</td></tr><tr><td>Cotton tipped applicators</td><td>MEDLINE</td><td>MDS202055</td><td>scrub head with saline</td></tr><tr><td>Tissue Tek O.C.T.</td><td>ASKURA FINETEK USA INC</td><td>4583</td><td>tissue embedding</td></tr><tr><td>anti-GFAP</td><td>Dako</td><td>CA93013</td><td>antibody for IHC</td></tr><tr><td>anti Ferritin</td><td>Sigma</td><td>F6136</td><td>antibody for IHC</td></tr><tr><td>VECTASTAIN Elite ABC&amp;nbsp; kit</td><td>Vector laboratories</td><td>PK-6100</td><td>IHC detection system</td></tr><tr><td>Permount Mounting Medium</td><td>Fisher Scientific</td><td>SP15-100</td><td></td></tr><tr><td>Aperio XT ScanScope scanner</td><td>Leica Microsystems Inc,</td><td></td><td>slides scanning</td></tr><tr><td>Leica AutoStainer XL</td><td>Leica the pathology Company</td><td>ST2010</td><td>H&amp;amp;E staining</td></tr><tr><td>DAB&amp;nbsp;</td><td>sigma</td><td>D3939</td><td>IHC detection system</td></tr></tbody></table>

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.

在这个模型中（ 图1 AC），有喘息和呼吸浅的短暂。意识（无意识）的损耗被定义为呼吸率或恢复正常的呼吸呼吸之前短暂终止下降。在头部的中心的冲击造成的短期无意识（7.5±4.7，7.8±5.5，10.2±8.8，在每个冲击9.5±8.0秒分开， 图1D）。小鼠的大脑表现出通过H＆E染色的组织学，这表明来自冲击（ 图2A）产生没有明显的结构损害或组织...

Watch this Scientific Journal Video about A Repetitive Concussive Head Injury Model in Mice at JoVE.com

A Repetitive Concussive Head Injury Model in Mice

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-repetitive-concussive-head-injury-model-in-mice

Research

JoVE Journal

Medicine

11.8K 次观看.  University of Florida. 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.

视频: A Repetitive Concussive Head Injury Model in Mice

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes 1,2. Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement 3,4. The resulting hematomas and lacerations cause a vascular response 3,5, and the morphological and functional damage of the white matter leads to diffuse axonal injury 6-8. Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure 9. Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals 10-12, which ultimately result in long-term neurological disabilities 13,14. Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair.
Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration 1. The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue 1,15. Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure 16,17. The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed skull 18. Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury 19. It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation 20.
We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP.

Lateral fluid percussion (LFP), an established model of traumatic brain injury in mice, is demonstrated. LFP fulfills three major criteria for animal models: validity, reliability and clinical relevance. The procedure, consisting of surgical craniotomy, fixation of hub followed by induction of injury, resulting in focal and diffuse injuries, is described.

侧向液压冲击：创伤性脑损伤小鼠模型

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and ...

科研

神经科学

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 ...

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 ...

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 ...

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 ...

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 ...

<meta charset="utf8"></head><body>CHILD 模型 — 回顾小鼠的青少年脑震荡和长期结果

A Pediatric Concussion Model in Mice: Closed Head Injury with Long-Term Disorders (CHILD)

Concussions and mild traumatic brain injuries (mTBI) during childhood represent a significant health endangerment, with many patients later in life exhibiting debilitating physiological, neurological, and psychosocial outcomes. The cellular and molecular pathophysiological mechanisms are relatively unknown, and this significant gap effectively precludes investigations into specific therapeutic strategies to mitigate chronic sequelae. No single animal concussion model recapitulates all the features reported in human subjects, and current models are designed to answer specific research questions. We set out to develop a juvenile concussion that recapitulates clinical early, and long-term symptomology encountered, termed Closed Head Injury with Long-term Disorder (CHILD). In this model, a concussive force via an electromagnetic impactor is delivered to the head of a lightly anesthetized unrestrained post-natal day 17 (P17) mouse, allowing free rotation of the head. Mice are placed on a tightly stretched tin foil across a stereotactic device, and the impactor is carefully aligned with the targeted cortical region. The electromagnetic impactor facilitates the selection of impact depth, dwell, and duration to determine injury severity. A strength of this model is that it allows head rotation, an important clinical feature. After impact, mice are immediately monitored for righting time and time to explore their environment, followed by their return to their dam. Increasing the severity of concussion results in intracranial bleeds in a subset of mice. Mice can be routinely monitored for behavior and neuroimaging over their lifespan, as desired. Various injury severities mimic the heterogeneous nature of juvenile concussions. The current standard CHILD model exhibits no skull fracture, no observable conventional neuroimaging change (similar to clinical), but leads to progressive and persistent neuronal death, altered diffusion MRI, modified neuronal activity and plasticity, increased gliosis, and progressive behavioral perturbations with age. In summary, this CHILD model mimics the early and long-term features observed in many clinical concussion patients.

<meta charset="utf8"></head><body>小鼠儿科脑震荡模型:闭合性颅脑损伤伴长期疾病 （CHILD）

Pediatric concussions can result in long-term sequelae with physiological and psychological perturbations. This pediatric concussion mouse model results in long-term neuroinflammation, white matter alterations, and neuronal modifications with behavioral dysfunction. The model can be adapted to differential impact locations or repeated concussions to assess lifetime changes.

小鼠儿科脑震荡模型:闭合性颅脑损伤伴长期疾病 （CHILD） 

Concussions and mild traumatic brain injuries (mTBI) during childhood represent a significant health endangerment, with many patients later in life ...

重复震荡颅脑损伤模型小鼠

摘要

探索更多视频

此视频中的章节

侧向液压冲击：创伤性脑损伤小鼠模型

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

创伤性脑损伤诱导受控皮质冲击的母模型

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

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

小鼠儿科脑震荡模型:闭合性颅脑损伤伴长期疾病（CHILD）

重复震荡颅脑损伤模型小鼠

摘要

探索更多视频

此视频中的章节

侧向液压冲击：创伤性脑损伤小鼠模型

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

创伤性脑损伤诱导受控皮质冲击的母模型

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

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

小鼠儿科脑震荡模型:闭合性颅脑损伤伴长期疾病 （CHILD）

小鼠儿科脑震荡模型:闭合性颅脑损伤伴长期疾病（CHILD）