Name: murine model of controlled cortical impact for the induction of traumatic brain injury
Uploaded: 2019-08-16T14:45:00
Description: Watch this Scientific Journal Video about Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury at JoVE.com

这项工作得到了美国国家卫生研究院GM117341助学金和美国外科医生学会C.詹姆斯·卡里科研究奖学金的资助。

所有程序都通过了西北大学机构动物护理和使用委员会的批准。C57BL/6小鼠是从杰克逊实验室购买的，并组在西北大学比较医学中心（伊利诺伊州芝加哥）的屏障设施中。所有动物都被安置在12/12小时的光/暗周期，免费获得食物和水。
1. 诱导麻醉
<ol><li>用氯胺酮（125毫克/千克）和木兰素（10毫克/千克）在腹内注射给小鼠麻醉。</li>
</ol>2. 每15分钟监测一次生?...

<ol>
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R., Brody, D., Cernak, I., McKee, A., Ruff, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Military-+and+sports-related+mild+traumatic+brain+injury:+clinical+presentation,+management,+and+long-term+consequences.">Military- and sports-related mild traumatic brain injury: clinical presentation, management, and long-term consequences.</a> Journal of Clinical Psychiatry. 74 (2), 180-188 (2013).</li><li>Martin, L. A., Neighbors, H. W., Griffith, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+experience+of+symptoms+of+depression+in+men+vs+women:+analysis+of+the+National+Comorbidity+Survey+Replication.">The experience of symptoms of depression in men vs women: analysis of the National Comorbidity Survey Replication.</a> JAMA Psychiatry. 70 (10), 1100-1106 (2013).</li><li>Makinde, H. M., Just, T. 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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=Expert+consensus+document:+Mind+the+gaps-advancing+research+into+short-term+and+long-term+neuropsychological+outcomes+of+youth+sports-related+concussions.">Expert consensus document: Mind the gaps-advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions.</a> Nature Reviews Neurology. 11 (4), 230-244 (2015).</li><li>Kramer, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Contribution+to+the+Theory+of+Cerebral+Concussion.">A Contribution to the Theory of Cerebral Concussion.</a> Annals of Surgery. 23 (2), 163-173 (1896).</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> Journal of Neurotrauma. 5 (1), 1-15 (1988).</li><li>Dixon, C. E., Clifton, G. L., Lighthall, J. W., Yaghmai, A. A., Hayes, R. L. <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> Journal of Neuroscience Methods. 39 (3), 253-262 (1991).</li><li>Schwulst, S. J., Trahanas, D. M., Saber, R., Perlman, H. <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-induced+alterations+in+peripheral+immunity.">Traumatic brain injury-induced alterations in peripheral immunity.</a> Journal of Trauma and Acute Care Surgery. 75 (5), 780-788 (2013).</li><li>Trahanas, D. M., Cuda, C. M., Perlman, H., Schwulst, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+Activation+of+Infiltrating+Monocyte-Derived+Cells+After+Mild+and+Severe+Traumatic+Brain+Injury.">Differential Activation of Infiltrating Monocyte-Derived Cells After Mild and Severe Traumatic Brain Injury.</a> Shock. 43 (3), 255-260 (2015).</li><li>Makinde, H. M., Cuda, C. M., Just, T. B., Perlman, H. R., Schwulst, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nonclassical+Monocytes+Mediate+Secondary+Injury,+Neurocognitive+Outcome,+and+Neutrophil+Infiltration+after+Traumatic+Brain+Injury.">Nonclassical Monocytes Mediate Secondary Injury, Neurocognitive Outcome, and Neutrophil Infiltration after Traumatic Brain Injury.</a> Journal of Immunology. 199 (10), 3583-3591 (2017).</li><li>Thompson, H. 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=Lateral+fluid+percussion+brain+injury:+a+15-year+review+and+evaluation.">Lateral fluid percussion brain injury: a 15-year review and evaluation.</a> Journal of Neurotrauma. 22 (1), 42-75 (2005).</li><li>Marmarou, 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=A+new+model+of+diffuse+brain+injury+in+rats.+Part+I:+Pathophysiology+and+biomechanics.">A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics.</a> Journal of Neurosurgery. 80 (2), 291-300 (1994).</li><li>Reneer, D. V., 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+multi-mode+shock+tube+for+investigation+of+blast-induced+traumatic+brain+injury.">A multi-mode shock tube for investigation of blast-induced traumatic brain injury.</a> Journal of Neurotrauma. 28 (1), 95-104 (2011).</li><li>Ma, X., Aravind, A., Pfister, B. J., Chandra, N., Haorah, J. <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+and+Assessment+of+Injury+Severity.">Animal Models of Traumatic Brain Injury and Assessment of Injury Severity.</a> Molecular Neurobiology. , (2019).</li><li>Makinde, H. 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=Monocyte+depletion+attenuates+the+development+of+posttraumatic+hydrocephalus+and+preserves+white+matter+integrity+after+traumatic+brain+injury.">Monocyte depletion attenuates the development of posttraumatic hydrocephalus and preserves white matter integrity after traumatic brain injury.</a> PLoS One. 13 (11), e0202722 (2018).</li><li>Osier, N. D., Dixon, C. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Controlled+Cortical+Impact+Model:+Applications,+Considerations+for+Researchers,+and+Future+Directions.">The Controlled Cortical Impact Model: Applications, Considerations for Researchers, and Future Directions.</a> Frontiers in Neurology. 7, 134 (2016).</li><li>Iaccarino, C., Carretta, A., Nicolosi, F., Morselli, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Epidemiology+of+severe+traumatic+brain+injury.">Epidemiology of severe traumatic brain injury.</a> Journal of Neurosurgical Sciences. 62 (5), 535-541 (2018).</li></ol>

有几个步骤对于应用可靠和一致的伤害至关重要。首先，小鼠必须到达外科麻醉的深平面，以确保在颅切除术期间没有运动。虽然许多麻醉方案可用于诱导啮齿动物的一般麻醉，但引起呼吸抑郁的麻醉剂，如吸入麻醉剂，在与严重的TBI结合时，可能导致呼吸停止。本协议使用氯胺酮（125毫克/千克）和木兰胺（10毫克/千克）注射在腹内。这种药物组合在5分钟内产生麻醉的手术平面，持续时间约为30...

美国疾病控制和预防中心估计，每年约有200万美国人遭受创伤性脑损伤（TBI）。事实上，TBI在美国所有与伤害有关的死亡中，超过30%的死亡率，每年医疗费用接近800亿美元，每人每年在严重的TBI3、4、5中生存近400万美元。TBI的影响突出表现在其幸存者遭受的重大长期神经认知和神经精神并发症与行为，认知和运动损伤的阴险开始称为慢性创伤性脑病（CTE）6,7,8,9,10.即使是亚临床脑震荡事件——那些不导致临床症状的影响——也可能导致长期神经功能障碍11、12。
研究TBI的动物模型从1800年末开始被采用。在 20 世纪 80 年代，开发了一种用于建模 TBI 的气动冲击器。这种方法现在被称为受控皮质撞击（CCI）14。CCI的控制和可重复性使研究人员将模型调整为啮齿动物15。我们的实验室使用这种模型，通过市售的冲击器和电子驱动装置16、17诱导TBI。该模型能够根据所使用的生物力学参数产生广泛的临床适用的TBI状态。在我们的实验室中引起严重损伤后，TBI大脑的由性评价显示，显著的叶边皮质和海马损失以及反向水肿和变形。此外，CCI产生一致的运动和认知功能损伤，通过行为测定18测量。CCI 的限制包括颅切除术和获取冲击器和驱动装置的费用。
TBI的其他几种模型存在，并在文献中得到了很好的建立，包括横向流体打击模型、降重模型和爆炸伤害模型19，20，21。虽然每种型号各有其独特优势，但其主要缺点是混合损伤、高死亡率和缺乏标准化，分别为22。此外，这些模型都没有提供 CCI 的精度、精度和可重复性。通过调整生物力学参数输入到驱动装置中，CCI 模型允许调查人员精确控制损伤的大小、损伤的深度以及施加到大脑的动能。这使得研究者能够将TBI的整个光谱应用于大脑的特定区域。它还允许从实验到实验的最大可重复性。

<table>
	<tbody>
		<tr>
			<td>AnaSed Injection Xylazine Sterile Solution</td>
			<td>LLOYD, Inc.</td>
			<td>5939911020</td>
		</tr>
		<tr>
			<td>Buprenorphine SR Lab 0.5mg/mL</td>
			<td>Zoopharm-Wildlife Pharmaceuticals USA</td>
			<td>BSRLAB0.5-182012</td>
		</tr>
		<tr>
			<td>High Speed Rotary Micromotor KiT0</td>
			<td>Foredom Electric Company</td>
			<td>K.1070</td>
		</tr>
		<tr>
			<td>Imapact one for Stereotaxix CCI</td>
			<td>Leica Biosystems Nussloch GmbH</td>
			<td>39463920</td>
		</tr>
		<tr>
			<td>Ketathesia Ketamine HCl Injection USP</td>
			<td>Henry Schein, Inc</td>
			<td>56344</td>
		</tr>
		<tr>
			<td>Mouse Specific Stereotaxic Base</td>
			<td>Leica Biosystems Nussloch GmbH</td>
			<td>39462980</td>
		</tr>
		<tr>
			<td>Trephines for Micro Drill</td>
			<td>Fine Science Tools, Inc</td>
			<td>18004-50</td>
		</tr>
	</tbody>
</table>

murine model of controlled cortical impact for the induction of traumatic brain injury

疾病控制和伤害预防中心估计，美国每年有近200万人遭受创伤性脑损伤（TBI）。事实上，TBI是造成所有与伤害有关的死亡率超过三分之一的因素。然而，TBI病理生理学的细胞和分子机制却知之甚少。因此，能够复制与人类患者TBI相关的损伤机制的TBI临床前模型是一项关键的研究需要。TBI 的受控皮质冲击 （CCI） 模型利用机械装置直接影响暴露的皮层。虽然没有一种模型能够全面概括人类患者中TBI的不同损伤模式和异质性，但CCI能够诱导广泛的临床应用TBI。此外，CCI 易于标准化，使调查人员能够跨实验和跨调查组比较结果。以下协议详细介绍了在 TBI 的鼠模型中使用市售影响装置的严重 CCI。

冲击器直接安装在立体框架上，分辨率高达 10 μm，用于控制冲击点、深度和穿透力。使用的电磁力可以产生1.5~6米/s的撞击速度。这使得在整个临床相关TBI范围内具有无与伦比的精度和可重复性。调查人员可以进行PILOT实验，改变损伤参数，如撞击器尖端尺寸、撞击速度和撞击深度，以确定最能产生所需伤害程度的参数。该协议描述了一个严重的TBI到左腹腔位区域，通过执行5毫米颅切除术2毫米左?...

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

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

创伤性脑损伤诱导受控皮质冲击的母模型

在这里，我们描述了通过开头控制皮质撞击诱导鼠外创伤性脑损伤的协议。

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

受控皮质撞击易于跨受试者和实验标准化，并允许将整个创伤性脑损伤谱应用到精确定义的大脑中的区域。证明这个程序是麦加伊斯兰，在我的实验室的研究技术人员。这种技术仍然是诱导啮齿动物创伤性脑损伤的最一致和可重复的形式。在开始该过程之前，将冲击装置连接到立体轴操作框架。将驱动装置与所需的生物力学参数隔离，以达到适当的实验速度和井速。戴上新的个人防护设备和无菌手套，并确认麻醉实验鼠对手趾捏缺乏反应。使用剪子为手术现场剃皮毛，并在动物的眼睛上涂抹软膏。然后将鼠标放入手术室，然后用三个连续的碘和酒精手术磨砂来准备剃光的皮肤。要诱发受控的皮质创伤性脑损伤，首先使用手术刀沿着头皮中线做一厘米的切口，以暴露头骨。从手术地点收回头皮，识别裸露头骨上的下垂和冠状缝合。要进行颅骨切除术，请配备一个5毫米的颤音钻头，以以最大速度激活钻头，并应用垂直于头骨的钻头，在下垂缝合线左侧两毫米，将两毫米的旋转到日冕缝合线，承受均匀的温和压力。当钻头穿透头骨时，会感觉到轻微的给予。使用钳子和小量表皮下针去除骨瓣，完全暴露底层杜拉母体，并旋转冲击器尖端到操作场。将立体框架的微型耳杆之间的双边时间骨骼固定起来，将切口锁定在切口夹内，以在鼠标头上形成稳定的三点固定。降低尖端，直到它与暴露的杜拉母体接触。仪器的接触传感器将发出声音提示，以提醒已进行接触。从零点收回冲击尖端，降低立体轴框架上的撞击器位置，以设置所需的冲击深度。然后将冲击器激活激活装置，然后将设备旋转回场外，以便将动物从框架中移走。受伤后，立即将无菌棉尖施用器直接压到头骨和受伤的皮质表面，以控制任何出血，并使用新的施用器干燥头骨。根据标准技术关闭颅骨切除术的头皮，并管理术后镇痛。然后将动物放在横向脱热恢复位置，在干净的预热笼中进行监测，直到完全下位，并在实验过程中每三天测量一次体重。所证明的伤害的传递导致宫内膜下体和亚布拉奇内出血。对严重伤害后创伤性脑损伤脑组织部分的组织学评估揭示了严重的气向性皮质和海马损失以及反向水肿和扭曲。严重损伤大脑的 MR 成像也显示渐进性组织损失和脑脊髓液的替换。受控皮质撞击可诱发可靠且一致的损伤，能够产生广泛的临床适用脑损伤。我们受控的皮质撞击方法生成严重创伤性脑损伤的murine模型，用于行为和成像分析，并生成用于分子和细胞分析的组织。

Research

JoVE Journal

Neuroscience

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

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

Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury

调查轻度创伤性脑损伤海马电路功能的改变

Traumatic Brain Injury (TBI) afflicts more than 1.7 million people in the United States each year and even mild TBI can lead to persistent neurological ...

A Novel In Vitro Model of Blast Traumatic Brain Injury

A Novel In Vitro Model of Blast Traumatic Brain Injury

一种新的脑外伤体损伤模型

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the ...

Effects of Blast-induced Neurotrauma on Pressurized Rodent Middle Cerebral Arteries

爆炸性神经损伤对压生啮鼠中脑动脉的影响

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral ...

Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice

研究小鼠创伤性脑损伤后凯库姆微生物群的改动

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also ...

Induction of Diffuse Axonal Brain Injury in Rats Based on Rotational Acceleration

基于旋转加速大鼠漫射性无羟基脑损伤的诱导

Traumatic brain injury (TBI) is a major cause of death and disability. Diffuse axonal injury (DAI) is the predominant mechanism of injury in a large ...

Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury

创伤性脑损伤的神经炎症和血流动力学反应的系统分析

Mild traumatic brain injuries (mTBIs) are a significant public health problem. Repeated exposure to mTBI can lead to cumulative, long-lasting functional ...

A Metric Test for Assessing Spatial Working Memory in Adult Rats Following Traumatic Brain Injury

创伤性脑损伤后评估成年大鼠空间工作记忆的指标测试

Impairments to sensory, short-term, and long-term memory are common side effects after traumatic brain injury (TBI). Due to the ethical limitations of ...

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

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

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 ...