这项研究是支持的，一部分由德意志研究联合会（DFG）的，项目广州PI 771/1-1; SFB 656“心血管分子成像”，德国明斯特（项目C6，Z2，B3，和PM3）;欧盟NOE“诊断分子成像迪米“（可湿性粉剂11.1和11.2）。这项研究还资助部分由英国心脏基金会，英国。

1。准备剪应力修饰符（袖口） <ol><li>剪应力修饰符 由两个纵向半圆柱与一个锥形腔。半壳是塑料铸造过程中产生的热塑性聚醚。投元素发送出去，同时仍然连接到亚军。因此，使用前不得不削减一半炮弹。每个投包含范围从150微米 - 300微米（下游终端的最低内径）的一半大小不同的炮弹。 </li><li>袖口准备应在手术显微镜下进行。 </li><li>保持钝钳袖口半壳，轻轻地削减自投使用锋利的手术刀。此过程会导致半壳前体，要进一步处理。 </li><li>广场甚至防滑板的半壳易制毒化学;修复钝钳和切割，沿预制切口正是在以REMOVE封闭结束。这将产生准备使用的袖口半壳。 </li><li>控制在显微镜下半壳，轻轻地清除任何剩余的锋利的边缘。锥形内腔诱导内剪应力的不同素质是必不可少的，上游和下游植入袖口。一个垂直内腔的半壳的外表面上的凹槽，作为一个线程终于坚持半弹在一起，形成功能袖的指导。 </li><li>存储袖口半壳，按大小分类，70％的乙醇，。 </li></ol> 2。植入右颈总动脉周围的袖口<ol><li> ApoE基因敲除小鼠10周龄左右，至少20克的重量。如果斑块的发展应进行调查，高胆固醇饮食下，这样一个西方型饮食开始前4周的袖口植入建议。 </li><li>整个手术过程应至少半无菌条件下下进行：穿手术衣，口罩，并盖和无菌手套。珠仪器灭菌消毒30秒，仪器和他们放在一个无菌的不透明表。当心！仪器冷却，然后再使用！ </li><li>鼠标放置在一个充满了3％异氟醚麻醉诱导室，直到它完全麻醉。验证响应脚趾捏的麻醉深度。另外，麻醉可进行腹腔注射（IP），氯胺酮（80毫克/公斤）和甲苯噻嗪（10毫克/千克）或由IACUC批准的替代麻醉药。腹腔注射，保持仰卧姿势鼠标和腹部左下象限注入麻醉剂。 </li><li>广场上加热外科板鼠标，在仰卧位。为了防止运行干燥滋润眼软膏（如Bepanthen眼睛和鼻子洗剂）的眼睛。传播脱颖而出和后腿的爪子和磁带盘。如果执行异氟醚麻醉，麻醉气体流量（2％异氟醚），通过提供一个小型的啮齿动物面具。 </li><li>卸下下颚骨之间的胸骨，要么用脱毛剂（如Pilca MED）或用细电动剃须刀（如威娜CONTURA）的头发。剃须要谨慎，以避免刺激皮肤。如果使用脱毛剂，给它穿透头发1-2分钟，随后，轻轻一擦，直到所有的头发和脱毛剂被删除。 </li><li>有准备不同大小（每个大小两个）和一个2.5厘米长的一块用于连接6-0丝线缝合在颈动脉闭塞部位的半壳的先前准备的袖口半壳。 </li><li>消毒优碘自由主义的经营领域。用锋利的小剪刀，打开一个4 - 5mm的内侧切口， 胸骨 （柄）从顶部开始的皮肤和颈部的基本筋膜。 </li><li>扩大对外开放，SHIFT右腮腺一边，插入手术吊具。然后直截了当地剖析深，到刚刚气管（从外科医生看来），其中右边的sternomastoideus肌肉穿过右肩胛舌骨肌离开，直到你能够识别脉动的右颈。 </li><li>使用非常细的角度或弯钳（如杜蒙＃5 / 45），解剖右颈总动脉，轻轻地去除周围结缔组织。迷走神经分离颈动脉 - 白色，纤维状的对象，直接沿颈 - 这一步是必要的，完全暴露船只。要小心，既不伤害的迷走神经，也不左侧颈内静脉，这也是紧密连接颈的一个分支。 </li><li>为了选择合适的袖带尺寸，比较的暴露颈动脉内径与袖口半壳直径：袖口流明的最大宽度应满足的颈动脉的外径。 </l我&gt; <li>现在，小心翼翼地把镊子尖的颈下，打开钳，线程片6-0丝线缝合颈下，形成一个循环。颈下方之间的循环和颈的地方之一袖口半壳。最大的缩小，一边是下游。 </li><li>第二袖半壳放置在顶部的颈环。 </li><li>轻轻拧紧缝合循环使用缝合钳和节点线程。这样做的运作剪应力修饰符组成。对于精确拟合的袖口，它是必不可少的，缝合预制沟槽内的袖口外表面完全运行。 </li><li>在原来的位置，近似将右腮腺和关闭的皮肤，可以使用6-0普理灵缝线的少量或者，你可以使用伤口剪辑。 </li><li>皮下注入单剂量5毫克/公斤卡洛芬（例如Rimadyl）提供预防性治疗疼痛和地方鼠标变暖室，直到它恢复。通常，这需要30-60分钟，使用氯胺酮/甲苯​​噻嗪麻醉时。当使用异氟醚吸入麻醉恢复期大幅缩短（10-20分钟）。 </li><li>根据我们的经验，动物重获袖口植入后24小时内正常重读活动的，由有经验的外科医生进行干预。但是，如果动物似乎是心疼甚至一天手术后，重复的镇痛治疗和咨询的兽医人员。 </li></ol> 3。 Explanting袖口和颈动脉<ol><li>组织学分析，颈动脉，在观察期结束收获。在出发explantation之前，动物被杀害，根据IACUC指引。 </li><li>如果打算再用袖口半壳，小心地取出所有组织碎片和连接缝合，从塑料的元素，DIS颈动脉secting，清洗和存储在70％的酒精溶液的一半炮弹。应该牢记，袖口是嵌入植入后的几个星期和解剖谨慎袖口为了不伤害血管壁结缔组织粘连。 </li><li>另外，袖口可explanted与颈动脉和嵌入式。塑料材质的袖口是耐正常固定的解决方案和用于石蜡包埋的溶剂。此外，嵌入式样品可以减少使用普通切片机配备了正常叶片。 </li></ol> 4。代表性的成果袖带要始终放在两个常见的颈动脉的动物（图1A，1B）周围 - 对侧作为对照。在图像袖口（图1B）提出的两个半壳圆锥形内腔是可见的。这是至关重要的圆锥形为EStablishing具有鲜明的血流动力学的三个地区。多普勒测量11和相应的流速计算相衬速度磁共振成像 12投典型的剪切应力诱导模式图2。 当袖带植入ApoE基因敲除小鼠喂食西方型饮食的改变流量动态挑起剪切应力引起动脉粥样硬化斑块的沉积（图3）：上游的锥形收缩低的层流剪应力导致动脉粥样硬化斑块的更大规模的发展脆弱的表型，特点是脂质核心的中央管腔只涵盖由薄的纤维帽（图3A1）。锥形内腔的袖口，导致流速增加。几乎没有斑块沉积是在这方面的观察。直接下游面积涡和振荡FLO立即动脉结果扩大的瓶颈的网站w参数，从而导致延长了一个更稳定的表型（即少脂是本地化更接近媒体的核心），斑块的发展。 <img alt="图1" src="/files/ftp_upload/3308/3308fig1.jpg" /> 图1剪应力修饰符- （一） 大会和安置示意图植入袖口：袖口放在周围的右颈总动脉（RCCA） -对侧（LCCA =左颈总动脉）作为控制。 （二）在小鼠体内MRI血管造影：在最大强度投影立体飞行MR血管造影的锥形收缩诱发投（白色箭头）是可见的（详细信息见12）。 （H =头，脚，R =右，L =左）。在右上角的一个宏观的角度对内腔和袖口半壳的外表面。组装时，两个半壳形成一个圆锥形的圆筒，该修改血流动力学内的船只在一个确定的方式。要确保正确的契合，袖口（黄色箭头）的外表面的凹槽作为连接缝合指导。 <img alt="图2" src="/files/ftp_upload/3308/3308fig2.jpg" /> 图2不同的血流动力学和剪应力的地区。植入袖口改变流动态和随后剪应力在颈内动脉收缩在一个定义的方式。在上面的示意图的表示不同的流动特性和当地剪应力的近似值（基于多普勒测量11 ）。下面，相应的流速为一个单一的动物植入袖口上游的MRI测量颈部横断面一个T1加权磁共振图像（相衬速度成像， 详见 12）所示。 剪切应力诱导ApoE基因敲除小鼠斑块的发展。左上角显示打开的脖子上的宏观性和高脂肪（西部型）饮食暴露在ApoE基因敲除小鼠颈动脉植入8周后剪应力图3 。周围的右颈总动脉（RCCA）修饰符。白色不透明的船只（*）的袖口上游地区对应到一个广泛的动脉粥样硬化斑块的沉积网站。黄色箭头表示的线程，它结合了两个半袖口。相比之下，有没有斑块沉积的迹象，在左冠状动脉（LCCA）。 （一） - （c）代表HE染色的ApoE基因敲除受西方型饮食8周后，植入的袖口鼠​​标的右颈动脉横截面。示意图给出相应的飞机（虚线）wherE的路段位于。 （一）上游的袖口动脉粥样硬化导致大量斑块沉积。大脂质核心（红色箭头），其中部分是靠近中央流明（详细A1）表征这些斑块脆弱性。 （二）在袖口的瓶颈平面几乎没有斑块的发展是显而易见的，而直接下游的袖口（三）振荡流导致中度斑块一个更稳定的类型（即少用或不用脂质核心）的发展。 （C1，C2 =半壳的袖口，P =斑块，星号=血管腔）

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作者什么都没有透露。

为了尽量减少实验误差，建议用几乎相同的年龄动物具有相​​同的饮食历史。最近发表的一份调查表明，剪应力调节剂，适用于野生型小鼠可能是一个很好的模式和改变血流动力学13诱导的内皮功能障碍的早期炎症反应的调查。然而，对于动脉粥样硬化斑块的发展转基因高脂血症小鼠模型的查询（如ApoE基因敲除小鼠）。每个小鼠模型的进展和斑块沉积的程度取决于使用饮食类型。在一?...

<table border="1"><tbody><tr><td> 名称 </td><td> 公司 </td><td> 评论 </td></tr><tr><td>剪应力调节剂（聚醚） </td><td> Promolding BV <a href="http://promolding.nl">http://promolding.nl</a> </td><td>铸件发送出去，同时仍然连接到亚军。因此，单一的元素都在使用前要削减。 </td></tr></tbody></table>

implantation of a carotid cuff for triggering shear-stress induced atherosclerosis in mice

它已被广泛接受，血管剪应力的改变引发的内皮细胞的炎性基因表达，从而诱发动脉粥样硬化（1和​​2审查）。剪切力的作用已被广泛研究，在体外血流动力学1,3,4对体外培养的内皮细胞的影响进行调查，并在较大 的动物和人类1,5,6,7,8的体内。然而，高度重复性的小动物模型，使斑块发展的剪应力的影响进行系统的调查是罕见的。近日，南等9中引入的一个小鼠模型中，结扎颈内动脉的分支创建一个低和振荡流的地区。尽管这种模式导致血管内皮功能障碍和高脂血症小鼠动脉粥样硬化病变的迅速形成，它不能被排除，所观察到的炎症反应是，至少有一部分，因此Øf内皮细胞和/或因结扎血管损伤。 为了避免这种局限性，剪应力修改袖口已经开发基于计算流体动力学，其锥体形内腔被选为低，高和振荡剪切应力定义的区域内常见的颈动脉10。通过应用这个模型中载脂蛋白E（APOE）基因敲除小鼠喂食高胆固醇，西方型饮食，血管病变发展的上游和下游，从袖口。其表型相关， 证实在体内磁共振成像（MRI）12区域流动的动态 11：低和层剪应力的袖口上游原因形成的一个更容易的表型广泛的斑块，而振荡剪切应力下游袖口诱导稳定动脉粥样硬化病变11。在这些地区的高剪切应力和高层流内的袖口，通常没有观察到动脉粥样硬化斑块。 总之，剪应力修改袖口过程是一个可靠的生产ApoE基因缺陷小鼠的表型不同的动脉粥样硬化病变的手术方式。

Watch this Scientific Journal Video about Implantation of a Carotid Cuff for Triggering Shear-stress Induced Atherosclerosis in Mice at JoVE.com

Implantation of a Carotid Cuff for Triggering Shear-stress Induced Atherosclerosis in Mice

本文介绍的收缩袖口的设计，以诱导小鼠左颈总动脉粥样硬化。由于其内腔的圆锥形植入袖口产生良好定义的低，高和振荡剪切引发动脉粥样硬化病变的不同炎症表型的发展压力的地区。

植入小鼠触发剪应力致动脉粥样硬化的颈袖

It is widely accepted that alterations in vascular shear stress trigger the expression of inflammatory genes in endothelial cells and thereby induce ...

implantation-carotid-cuff-for-triggering-shear-stress-induced

Research

JoVE Journal

Medicine

20.0K 次观看.  Westfälische Wilhelms-University Münster. 本文介绍的收缩袖口的设计，以诱导小鼠左颈总动脉粥样硬化。由于其内腔的圆锥形植入袖口产生良好定义的低，高和振荡剪切引发动脉粥样硬化病变的不同炎症表型的发展压力的地区。

视频: Implantation of a Carotid Cuff for Triggering Shear-stress Induced Atherosclerosis in Mice

A Model of Disturbed Flow-Induced Atherosclerosis in Mouse Carotid Artery by Partial Ligation and a Simple Method of RNA Isolation from Carotid Endothelium

Despite the well-known close association, direct evidence linking disturbed flow to atherogenesis has been lacking. We have recently used a modified version of carotid partial ligation methods [1,2] to show that it acutely induces low and oscillatory flow conditions, two key characteristics of disturbed flow, in the mouse common carotid artery. Using this model, we have provided direct evidence that disturbed flow indeed leads to rapid and robust atherosclerosis development in Apolipoprotein E knockout mouse [3]. We also developed a method of endothelial RNA preparation with high purity from the mouse carotid intima [3]. Using this mouse model and method, we found that partial ligation causes endothelial dysfunction in a week, followed by robust and rapid atheroma formation in two weeks in a hyperlipidemic mouse model along with features of complex lesion formation such as intraplaque neovascularization by four weeks. This rapid in vivo model and the endothelial RNA preparation method could be used to determine molecular mechanisms underlying flow-dependent regulation of vascular biology and diseases. Also, it could be used to test various therapeutic interventions targeting endothelial dysfunction and atherosclerosis in considerably reduced study duration.

This describes a partial carotid ligation surgery, which causes disturbed flow conditions and subsequent atherosclerosis development (in two weeks) with intraplaque neo-vascularization (in four weeks) in the mouse common carotid artery. We also describe a novel method of RNA isolation from the carotid intima, providing high purity endothelial RNA.

一个型号的不安流致动脉粥样硬化小鼠颈动脉部分结扎术和颈动脉内皮细胞的RNA分离的简单方法

Despite the well-known close association, direct evidence linking disturbed flow to atherogenesis has been lacking. We have recently used a modified ...

科研

医学

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings.

A model of stent implantation in mouse carotid artery is described. Compared to other similar methods, this procedure is very rapid, simple and accessible, offering the possibility to study in a convenient way the vascular wall reaction to different drug-eluting stents and the molecular mechanisms of restenosis.

颈动脉支架植入再狭窄的研究的小鼠模型

Despite  the considerable progress made in the stent development in the last decades,  cardiovascular diseases remain the main cause of death in western ...

Tibial Nerve Transection - A Standardized Model for Denervation-induced Skeletal Muscle Atrophy in Mice

The tibial nerve transection model is a well-tolerated, validated, and reproducible model of denervation-induced skeletal muscle atrophy in rodents. Although originally developed and used extensively in the rat due to its larger size, the tibial nerve in mice is big enough that it can be easily manipulated with either crush or transection, leaving the peroneal and sural nerve branches of the sciatic nerve intact and thereby preserving their target muscles. Thus, this model offers the advantages of inducing less morbidity and impediment of ambulation than the sciatic nerve transection model and also allows investigators to study the physiologic, cellular and molecular biologic mechanisms regulating the process of muscle atrophy in genetically engineered mice. The tibial nerve supplies the gastrocnemius, soleus and plantaris muscles, so its transection permits the study of denervated skeletal muscle composed of fast twitch type II fibers and/or slow twitch type I fibers. Here we demonstrate the tibial nerve transection model in the C57Black6 mouse. We assess the atrophy of the gastrocnemius muscle, as a representative muscle, at 1, 2, and 4 weeks post-denervation by measuring muscle weights and fiber type specific cross-sectional area on paraffin-embedded histologic sections immunostained for fast twitch myosin.

The tibial nerve transection model is a well-tolerated, validated, and reproducible model of skeletal muscle atrophy. The model surgical protocol is described and demonstrated in C57Black6 mice. &#160;

胫骨神经切断术 - 一个标准化的模型失神经诱导小鼠骨骼肌

The tibial nerve transection model is a well-tolerated, validated, and reproducible model of denervation-induced skeletal muscle atrophy in rodents. ...

Inducing Myointimal Hyperplasia Versus Atherosclerosis in Mice: An Introduction of Two Valid Models

Various in vivo laboratory rodent models for the induction of artery stenosis have been established to mimic diseases that include arterial plaque formation and stenosis, as observed for example in ischemic heart disease. Two highly reproducible mouse models&#160;&#8211;&#160;both resulting in artery stenosis but each underlying a different pathway of development&#160;&#8211; are introduced here. The models represent the two most common causes of artery stenosis; namely one mouse model for each myointimal hyperplasia, and atherosclerosis are shown. To induce myointimal hyperplasia, a balloon catheter injury of the abdominal aorta is performed. For the development of atherosclerotic plaque, the ApoE -/- mouse model in combination with western fatty diet is used. Different model-adapted options for the measurement and evaluation of the results are named and described in this manuscript. The introduction and comparison of these two models provides information for scientists to choose the appropriate artery stenosis model in accordance to the scientific question asked.

This video shows two models of intimal plaque development in murine arteries and emphasizes the differences in myointimal hyperplasia and atherosclerosis.

诱导肌内膜增生对战动脉粥样硬化小鼠：两种有效的模型介绍

Various in vivo laboratory rodent models for the induction of artery stenosis have been established to mimic diseases that include arterial plaque ...

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study model. As the use of mouse models are often a vital step in preclinical drug discovery and drug development1-8, it is necessary to design a system to introduce drugs into mice in a uniform, reproducible manner. Ideally, the system should permit the collection of blood samples at regular intervals over a set time course. The ability to measure drug concentrations by mass-spectrometry, has allowed investigators to follow the changes in plasma drug levels over time in individual mice1, 9, 10. In this study, paclitaxel was introduced into transgenic mice as a continuous arterial infusion over three hours, while blood samples were simultaneously taken by retro-orbital bleeds at set time points. Carotid artery infusions are a potential alternative to jugular vein infusions, when factors such as mammary tumors or other obstructions make jugular infusions impractical. Using this technique, paclitaxel concentrations in plasma and tissue achieved similar levels as compared to jugular infusion. In this tutorial, we will demonstrate how to successfully catheterize the carotid artery by preparing an optimized catheter for the individual mouse model, then show how to insert and secure the catheter into the mouse carotid artery, thread the end of the catheter out through the back of the mouse&#8217;s neck, and hook the mouse to a pump to deliver a controlled rate of drug influx. Multiple low volume retro-orbital bleeds allow for analysis of plasma drug concentrations over time.

This method was developed with the goal of delivering a steady drug solution via the carotid artery, to assess the pharmacokinetics of novel drugs in mouse models.

颈动脉输液的紫杉烷类化合物在小鼠体内的药代动力学和药效学分析

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

Triggering Reactive Gliosis In Vivo by a Forebrain Stab Injury

Following injury to the CNS, astrocytes undergo a broad range of biochemical, morphological, and molecular changes collectively referred to as reactive astrogliosis. Reactive astrocytes exert both inflammatory and protective effects that inhibit and promote, respectively, neural repair. The mechanisms underlying the diverse functional properties of reactive astrogliosis are not well understood. Achieving a greater understanding of these mechanisms is critical to developing therapeutic strategies to treat the injured CNS. Here we demonstrate a method to trigger reactive astrogliosis in the adult mouse forebrain using a forebrain stab lesion. This lesion model is simple, reliable, and requires only a stereotaxic device and a scalpel blade to produce the injury. The use of stab lesions as an injury model in the forebrain is well established and amenable to studies addressing a broad range of neuropathological outcomes, such as neuronal degeneration, neuroinflammation, and disruptions in the blood brain barrier (BBB). Thus, the forebrain stab injury model serves as a powerful tool that can be applied for a broad range of studies on the CNS response to trauma.

Triggering Reactive Gliosis In Vivo by a Forebrain Stab Injury

This article describes a detailed protocol to produce a forebrain stab injury in adult mice. The stab injury induces severe reactive gliosis and glial scar formation which can be subsequently examined by standard immunohistochemistry methods.

触发反应胶质细胞增生<em&gt;在体内</em&gt;由前脑锐器伤

Following injury to the CNS, astrocytes undergo a broad range of biochemical, morphological, and molecular changes collectively referred to as reactive ...

Surgical Approach for Middle Cerebral Artery Occlusion and Reperfusion Induced Stroke in Mice

Stroke is a leading cause of death worldwide and continues to be one of the major causes of long-term adult disabilities. About 87% of strokes are ischemic in origin and occur in the territory of the middle cerebral artery (MCA). Currently the only Food and Drug Administration (FDA) approved drug for the treatment of this devastating disease is tissue plasminogen activator (tPA). However, tPA has a small therapeutic window for administration (3 - 6 hr), and is only effective in 4% of the patients who actually receive it. Current research focuses on understanding the pathophysiology of stroke in order to find potential therapeutic targets. Thus, reliable models are crucial, and the MCA occlusion (MCAo) model (also termed the intraluminal filament or suture model) is deemed to be the most clinically relevant surgical model of ischemic stroke, and is fairly non-invasive and easily reproducible. Typically the MCAo model is used with rodents, especially with mice due to all the genetic variations available for this species. Here we describe (and present in the video) how to successfully perform the MCAo model (with reperfusion) in mice to generate reliable and reproducible data.

In order to understand the pathophysiology of stroke, it is important to use reliable models. This paper will describe one of the most frequently used stroke models in mice, termed the middle cerebral artery occlusion (MCAo) model (also termed the intraluminal filament or suture model) with reperfusion.

对大脑中动脉闭塞再灌注损伤诱发中风小鼠的手术方法

Stroke is a leading cause of death worldwide and continues to be one of the major causes of long-term adult disabilities. About 87% of strokes are ...

Induction of Accelerated Atherosclerosis in Mice: The "Wire-Injury" Model

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. Moreover, by rupture of the defective vascular wall, atherosclerosis induces occlusive thrombus formation, which represents the main cause of myocardial infarction or stroke and the most frequent cause of death. Despite the advances in the cardiovascular field, many questions remain unanswered, and additional basic research is essential to improve our understanding of the molecular mechanisms during atherosclerosis and its effects. Due to limited clinical studies, there is a need for representative animal models recreating atherosclerotic conditions such as neointima formation after stent implantation, balloon angioplasty, or endarterectomy. Since the mouse presents many advantages and is the most frequently used model for studying molecular processes, the current study proposes an invasive procedure of endothelial denudation, also known as the wire-injury model, which is representative of the human condition of neointima formation in arteries after revascularization procedures.

Induction of Accelerated Atherosclerosis in Mice: The &quot;Wire-Injury&quot; Model

This study describes an invasive procedure for the induction of accelerated atherosclerosis in mice. In comparison to other methods using electric- or cryo-induced injury, mechanical-induced injury mimics the human condition of restenosis after revascularization therapies and is ideal for the study of the molecular mechanisms involved.

小鼠加速动脉硬化的诱导："电线损伤"模型

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. ...

Mouse Model for Pancreas Transplantation Using a Modified Cuff Technique

Mouse models have several advantages in transplantation research, including easy handling, a variety of genetically well-defined strains, and the availability of the widest range of molecular probes and reagents to perform in vivo as well as in vitro studies. Based on our experience with various murine transplantation models, we developed a heterotopic pancreas transplantation model in mice with the intent to analyze mechanisms underlying severe ischemia reperfusion injury-associated early graft damage. In contrast to previously described techniques using suture techniques, herein we describe a new procedure using a non-suture cuff technique. 
In recent years, we have performed more than 300 pancreas transplantations in mice with an overall success rate of &gt;90%, a success rate never described before in mouse pancreas transplantation. The backbone of this non-suture cuff technique for graft revascularization consists of two major steps: (I) pulling the recipient vessel over a polyethylene/polyamide cuff and fixing it with a circumferential ligature, and (II) placing the donor vessel over the everted recipient vessel and fixing it with a second circumferential ligature. The resultant continuity of the endothelial layer results in less thrombogenic lesions with high patency rates and, finally, high success rates.
In this model, arterial anastomosis is achieved by pulling the abdominal aorta of the donor graft over the everted common carotid artery of the recipient animal. Venous drainage of the graft is achieved by pulling the portal vein of the graft over the everted external jugular vein of the recipient. This manuscript provides details and crucial steps of the organ recovery and organ implantation procedures, which will allow researchers with microsurgical skills to perform the transplantation successfully in their laboratories.

Among abdominal solid organ transplantation, pancreatic grafts are prone to develop severe ischemia reperfusion injury-associated graft damage, leading eventually to early graft loss. This protocol describes a model of murine pancreas transplantation using a non-suture cuff technique, ideally suited for analyzing these early, deleterious damages.

应用改良袖套技术的小鼠胰腺移植模型

Mouse models have several advantages in transplantation research, including easy handling, a variety of genetically well-defined strains, and the ...

Ferric Chloride-induced Canine Carotid Artery Thrombosis: A Large Animal Model of Vascular Injury

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, we have translated a vascular injury model from a small animal into a large animal (canine), with slight modifications that can be used for pre-clinical screening of prophylactic and thrombolytic agents. In addition to the surgical methods, the modified protocol describes the step-by-step methods to assess carotid artery canalization by angiography, detailed instructions to process both the brain and carotid artery for histological analysis to verify carotid canalization and cerebral hemorrhage, and specific parameters to complete an assessment of downstream thromboembolic events by utilizing magnetic resonance imaging (MRI). In addition, specific procedural changes from the previously well-established small animal model necessary to translate into a large animal (canine) vascular injury are discussed.

Here, we present the modifications necessary to a well characterized and commonly used small animal ferric chloride-induced (FeCl3) carotid artery injury model for use in a large animal vascular injury model. The resulting model can be utilized for pre-clinical trial assessment of both prophylactic and thrombolytic pharmacological and mechanical interventions.

氯化铁诱导的犬颈动脉血栓形成: 一种大的血管损伤动物模型

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, ...