这项工作是由来自印第安纳州脊髓和脑损伤的研究资助（SCBI 200-12）提供资金支持，拉尔夫W.和格雷斯M.沙氏研究奖，美国印第安纳大学生物研究基金，美国国立卫生研究院资助RR025761和1R21NS072631-01A。

动物护理 男C57 BL / 6小鼠群养，并保持在一个12/12小时亮/暗周期，自由地获取食物和水随意 。在这个协议中使用的动物是10-12周龄。所有程序均在批准的印第安纳大学的动物护理和使用委员会的协议执行。 1，手术准备<ol><li>使用氯胺酮/甲苯​​噻嗪混合物（87.7毫克/毫升氯胺酮和12.3毫克/毫升甲苯噻嗪）麻醉小鼠，并通过腹腔注射给药（1毫升/千克）。 </li><li>剃两耳之间的小鼠头部。 </li><li>适用于石油基果冻到鼠标的眼睛，以防止在手术过程中变干。 </li><li>请用10％碘的剃光区域。然后用70％的酒精擦拭脱碘。 </li><li>用耳棒和导板固定鼠标头部立体定位框架。保证大脑是稳定的。 </li></ol> 2。骨瓣</P&gt; <ol><li>使头部用剪刀中间有纵形切口。用止血钳保持皮肤脱落的左侧。 </li><li>用棉签除去血液和组织中的骨，以暴露颅骨。允许暴露颅骨干燥1分钟。 </li><li>使用镊子施加压力，并确保该头骨保持不动。确定解剖标志LAMBDA（尾椎方面）和前囟门（正面的方面）。绘制在Lambda和前囟门的中心圆直径4mm和0.5 mm远离中线。 </li><li>使用钻孔沿标记的圆圈切割。轻轻地吹骨扬灰了。不要穿过骨完全钻，以免损坏硬脑膜。 </li><li>使用镊子去除骨暴露硬脑膜。 </li></ol> 3。嵌塞冲击系统包括控制箱设置影响的参数，一个致动器来执行嵌塞，和立体定位框架，以确保该行为uator和鼠标头的影响。 <ol><li>预先设定的致动器的速度，以6米/秒的手术前。 </li><li>预先设置不同的变形深度诱导不同的损伤严重性。为0.0-0.2毫米，0.5-1.0毫米，1.2-2.0毫米深的变形会导致轻度，中度，重度科技企业孵化器，分别为。该协议解释了如何通过使用3米/秒的速度实现了适度重型颅脑损伤1毫米变形深度。 </li><li>连接所述致动器在支架中的立体定位框架，并使用显微操作器移动它来固定致动器（直径3mm），在打开头骨区域的中心的圆的，平的端部。然后调节笔尖在平行于冲击部位的表面的角度。 </li><li>通过向下移动的扩展模型中执行器，直到笔尖接触撞击点的表面建立的零点。然后设置Z通道的立体定向控制面板零上。 </li><li>收回撞击尖同时移动驱动器下降1毫米。 </li><li>击中冲击按钮罢工的损伤部位，达到1毫米的变形深度。 </li></ol> 4，损伤部位封闭<ol><li>用棉签涂药，以消除任何血继的影响，但不碰损伤区域。 </li><li>放置在一个温暖的鼠标垫，以保持体温。 </li><li>一旦出血停止后，缝合关闭伤口。将动物放回笼子清洁并允许其从手术中恢复过夜的暖垫。 </li><li>管理丁丙诺啡0.05-0.10毫克/公斤SQ每天8-12小时的手术后2天。 </li></ol>

<ol>
	<li>Menon, D. K., Schwab, K., 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=Position+statement:+definition+of+traumatic+brain+injury.">Position statement: definition of traumatic brain injury.</a> Arch Phys Med Rehabil. 91 (11), 1637-1640 (2010).</li><li>Lighthall, J. W., Dixon, C. E., 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=Experimental+models+of+brain+injury.">Experimental models of brain injury.</a> J Neurotrauma. 6 (2), 83-97 (1989).</li><li>Dixon, C. E., Clfton, G. 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=A+controlled+cortical+impact+model+of+traumatic+brain+injury+in+the+rat.">A controlled cortical impact model of traumatic brain injury in the rat.</a> J Neurosci Methods. 39 (3), 253-262 (1991).</li><li>Scheff, S. W., Baldwin, S. A., 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=Morris+water+maze+deficits+in+rats+following+traumatic+brain+injury:+lateral+controlled+cortical+impact.">Morris water maze deficits in rats following traumatic brain injury: lateral controlled cortical impact.</a> J Neurotrauma. 14 (9), 615-627 (1997).</li><li>Smith, D. H., Soares, H. 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=A+model+of+parasagittal+controlled+cortical+impact+in+the+mouse:+cognitive+and+histopathologic+effects.">A model of parasagittal controlled cortical impact in the mouse: cognitive and histopathologic effects.</a> J Neurotrauma. 12 (2), 169-178 (1995).</li><li>Hannay, H. J., Feldman, 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=Validation+of+a+controlled+cortical+impact+model+of+head+injury+in+mice.">Validation of a controlled cortical impact model of head injury in mice.</a> J Neurotrauma. 16 (11), 1103-1114 (1999).</li><li>Natale, J. E., Ahmed, F., 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=Gene+expression+profile+changes+are+commonly+modulated+across+models+and+species+after+traumatic+brain+injury.">Gene expression profile changes are commonly modulated across models and species after traumatic brain injury.</a> J Neurotrauma. 20 (10), 907-927 (2003).</li><li>Anderson, R. W., Brown, C. 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=Impact+mechanics+and+axonal+injury+in+a+sheep+model.">Impact mechanics and axonal injury in a sheep model.</a> J Neurotrauma. 20 (10), 961-974 (2003).</li><li>Lighthall, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controlled+cortical+impact:+a+new+experimental+brain+injury+model.">Controlled cortical impact: a new experimental brain injury model.</a> J Neurotrauma. 5 (1), 1-15 (1988).</li><li>Chen, S., Pickard, J. 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=Time+course+of+cellular+pathology+after+controlled+cortical+impact+injury.">Time course of cellular pathology after controlled cortical impact injury.</a> Exp Neurol. 182 (1), 87-102 (2003).</li><li>Long, J. B., Bentley, T. 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K., 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=Neutrophil+accumulation+after+traumatic+brain+injury+in+rats:+comparison+of+weight+drop+and+controlled+cortical+impact+models.">Neutrophil accumulation after traumatic brain injury in rats: comparison of weight drop and controlled cortical impact models.</a> J Neurotrauma. 11 (5), 499-506 (1994).</li><li>Werner, C., Engelhard, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathophysiology+of+traumatic+brain+injury.">Pathophysiology of traumatic brain injury.</a> Br J Anaesth. 99 (1), 4-9 (2007).</li><li>Colicos, M. A., Dixon, C. E., 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=Delayed,+selective+neuronal+death+following+experimental+cortical+impact+injury+in+rats:+possible+role+in+memory+deficits.">Delayed, selective neuronal death following experimental cortical impact injury in rats: possible role in memory deficits.</a> Brain Res. 739 (1-2), 111-119 (1996).</li><li>Raghavendra Rao, V. L., Dogan, A., 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=Traumatic+brain+injury+leads+to+increased+expression+of+peripheral-type+benzodiazepine+receptors,+neuronal+death,+and+activation+of+astrocytes+and+microglia+in+rat+thalamus.">Traumatic brain injury leads to increased expression of peripheral-type benzodiazepine receptors, neuronal death, and activation of astrocytes and microglia in rat thalamus.</a> Exp Neurol. 161 (1), 102-114 (2000).</li><li>Gao, X., Chen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Moderate+traumatic+brain+injury+promotes+neural+precursor+proliferation+without+increasing+neurogenesis+in+the+adult+hippocampus.">Moderate traumatic brain injury promotes neural precursor proliferation without increasing neurogenesis in the adult hippocampus.</a> Exp Neurol. 239, 38-48 (2013).</li></ol>

The authors have nothing to disclose.

为成功地产生一致的孵化器的数量使用电子冲击磁体系统以引起CCI中最关键的步骤是:1）稳定地固定在鼠标头在立体定位框架; 2）产生的小鼠之间的骨窗的大小相同，没有骨瓣期间根据其损伤硬膜去除骨; 3）正确定位的影响，提示在开区的中心，影响之前确定的零点。 鼠标头必须固定在立体定位框架的影响之前非常紧密。内固定松动会产生大的变化伤害的水平。为了确保固定...

创伤性脑损伤（TBI）被定义为改变在脑功能，或其他证据脑病理学的，引起的外力1。科技企业孵化器仍然是一个严重的健康问题，在世界各地，特别是在美国。根据疾病控制中心和预防，至少170万科技企业孵化器，每年发生在美国造成的所有伤害相关的死亡的30.5％。 2000年，直接医疗费用和科技企业孵化器的间接成本总额估计为76.5十亿在美国孤单。尽管在过去几十年的技术和治疗的进步已经改善的生活质量和长度为那些从孵化器的数量的痛苦，没有有效的药物或预防性治疗目前存在。由于复杂性和科技企业孵化器，包括组织病变，细胞死亡和轴突变性广泛深远的影响，没有两个伤害是相同的;因此，对动物无电流TBI模型准确地再现TBI的各个方面所看到的人类。然而，动物模型并提供生产所需的调查TBI的目的是进一步了解科技企业孵化器的临床表现，希望不同的效果几乎相同的伤害的能力。 受控皮质冲击（CCI）模型使用了一个冲击系统提供物理冲击到动物的暴露硬脑膜。它诱导科技企业孵化器的范围从轻微到严重类似的经历的人。这种损伤是第一特征的白鼬2和后来被改编为在大鼠3,4，鼠标5-7，和羊8使用。由于第一特征，损伤部位已被放置两过中线2,9和外侧皮质10。 CCI提供了调查的影响和潜在的治疗科技企业孵化器的一个简单而准确的方法。 除了在CCI模型中，流体打击乐器和重量下降模型是共mmonly用于生产科技企业孵化器。然而，这些模型存在的局限性，包括更少的控制参数的伤害，产生不可见人的科技企业孵化器histopathalogical变化，意外死亡的小鼠3,5,10发病较多。冲击波模型也用于生产科技企业孵化器。虽然冲击波模式不会重现见过histopathalogical变化下的机械冲击，这种模式并准确地生成特别是军事人员11经历科技企业孵化器。该控制皮层的影响模型是很容易控制，由于精确控制变形参数，如时间，速度和冲击5的深度。这样的精度，使整个动物更可行的整组复制几乎相同的伤害。最重要的是，CCI再现科技企业孵化器与出现在人类的科技企业孵化器12的功能。然而，没有一个单一的动物模型是在病理性重现陈的完整光谱完全成功GES脑外伤后观察。进一步的研究是必要的，以充分揭示脑外伤后发生的急性和慢性的变化。 两种类型的伤害发生下列脑外伤:主要和次要受伤。原发性损伤发生在撞击时刻，而不是治疗性的治疗敏感;然而，在初始损伤后持续存在二次伤害受治疗13。该控制皮层的影响模型产生的原发性损伤，从而使研究人员调查TBI的影响和潜在的治疗治疗继发性损伤的潜在的长期影响。使用CCI模型潜在的研究领域包括神经元死亡，脑水肿，神经，血管的影响，histopathalogical变化，记忆障碍，更3,13-16。

<table><tbody><tr><td>Povidone-iodine 7.5%</td><td>Purdue product L.P.</td><td></td><td>Surgical scrub</td></tr><tr><td>Cotton tipped applicators</td><td>Henry Schein</td><td>100-6015</td><td>Remove blood and debris</td></tr><tr><td>Scissor</td><td>Fine Science Tools</td><td>14084-08</td><td>Surgery</td></tr><tr><td>Forcept</td><td>Fine Science Tools</td><td>11293-00</td><td>Surgery</td></tr><tr><td>Hemostat</td><td>Fine Science Tools</td><td>13021-12</td><td>Surgery</td></tr><tr><td>Rechargeable Cordless Micro Drill</td><td>Stoelting</td><td>58610</td><td>Combine with Burrs for generating the bone window</td></tr><tr><td>Burrs for Micro Drill</td><td>Fine Science Tools</td><td>19007-05</td><td></td></tr><tr><td>Suture monofilament</td><td>Ethicon</td><td>G697</td><td>Suture</td></tr><tr><td>tert-Amyl alcohol</td><td>Sigma</td><td>152463-250ML</td><td>Making 2.5% Avertin</td></tr><tr><td>2,2,2-Tribromoethanol</td><td>Sigma</td><td>T48402-25G</td><td>Making 2.5% Avertin</td></tr></tbody></table>

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.

该控制皮层的影响模型产生科技企业孵化器范围的严重程度从轻微到严重。撞击后颅肿胀的量，出血，并在冲击地点颅失真将揭示从速度和变形深度参数造成的损伤程度。温和的科技企业孵化器导致颅肿胀在撞击地点和轻微出血，由于有限的硬脑膜违约。适度表现出脑外伤颅内肿胀，出血增多，由于硬脑膜违反嵌塞后（ 图1）。中度和重度TBI之间的差别可能是难以区分，直到上观察用...

Watch this Scientific Journal Video about Controlled Cortical Impact Model for Traumatic Brain Injury at JoVE.com

Controlled Cortical Impact Model for Traumatic Brain Injury

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, ...

controlled-cortical-impact-model-for-traumatic-brain-injury

Research

JoVE Journal

Medicine

28.4K 次观看.  Indiana University School of Medicine. 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.

视频: Controlled Cortical Impact Model for Traumatic Brain Injury

Controlled Cortical Impact Model of Mouse Brain Injury with Therapeutic Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Cells

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. Disease pathology due to TBI progresses from the primary mechanical insult to secondary injury processes, including apoptosis and inflammation. Animal modeling has been valuable in the search to unravel injury mechanisms and evaluate potential neuroprotective therapies. This protocol describes the controlled cortical impact (CCI) model of focal, open-head TBI. Specifically, parameters for producing a mild unilateral cortical injury are described. Behavioral consequences of CCI are analyzed using the adhesive tape removal test of bilateral sensorimotor integration. Regarding experimental therapy for TBI pathology, this protocol also illustrates a process for transplanting cultured cells into the brain. Neural cell cultures derived from human induced pluripotent stem cells (hiPSCs) were chosen for their potential to show superior functional restoration in human TBI patients. Chronic survival of hiPSCs in the host mouse brain tissue is detected using a modified DAB immunohistochemical process.

This protocol demonstrates methodologies for a mouse model of open-skull traumatic brain injury and transplantation of cultured human induced pluripotent stem cell-derived cells into the injury site. Behavioral and histologic tests of outcomes from these procedures are also described in brief.

人类诱导多能干细胞衍生神经细胞治疗移植小鼠脑损伤控制皮质影响模型

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. Disease pathology due to TBI progresses from the primary mechanical ...

科研

发育生物学

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 ...

医学

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 ...

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

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 ...

A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the pathophysiological mechanism and to develop effective therapeutic strategy for this devastating neurological disorder. Intraparenchymal hemorrhage and post-traumatic inflammatory response induced by initial physical impact can aggravate microglia/macrophage activation and neuroinflammation which subsequently worsen brain pathology. We provide here a controlled cortical impact (CCI) protocol that can reproduce experimental cortical contusion in mice by using a pneumatic impactor system to deliver mechanical force with controllable magnitude and velocity onto the dural surface. This preclinical model allows researchers to induce moderately severe focal cerebral contusion in mice and to investigate a wide range of post-traumatic pathological progressions including hemorrhage contusion, microglia/macrophage activation, iron toxicity, axonal injury, as well as short-term and long-term neurobehavioral deficits. The present protocol can be useful for exploring the long-term effects of and potential interventions for cerebral contusion.

<meta charset="utf8"></head><body>创伤性出血挫伤和神经炎症的临床前受控皮质影响模型

Intraparenchymal hemorrhage and neuroinflammation accompanied by cerebral contusion can trigger severe secondary brain injury. This protocol details a mouse controlled cortical impact (CCI) model allowing researchers to study hemorrhage contusion and post-traumatic immune responses and explore potential therapeutics.

创伤性出血挫伤和神经炎症的临床前受控皮质影响模型

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the ...

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 ...

控制皮层影响模型创伤性脑损伤

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创伤性出血挫伤和神经炎症的临床前受控皮质影响模型

创伤性出血挫伤和神经炎症的临床前受控皮质影响模型

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