此设备的发展，支持LISA有限公司，美国肯塔基州路易斯维尔。我们也承认诺顿医疗保健，肯塔基州路易斯维尔到CBS，和NS052290 NS050243 NIH，，和NS059622到XMX的持续支持。

1。动物脊柱稳定剂的制备及应用鼠标颈椎凹腹面从横向视图。 C3至T1的棘突小而易碎，因此，不适合于稳定椎通常描述3,4。我们建议进行横向面固定，脊柱稳定。固定装置由一个U形的金属通道，支持鼠标和两个可调节的不锈钢臂夹住各个方面的横向。这提供了极好的固定目标椎。脊柱内固定后，脊柱轻度升高颈椎曲率变平，以提供更好的暴露的脊髓。 <ol><li>消毒手术器械以下：2-3双钳，2对microscissors，30 G针，缝合针器，皮肤剪辑，剪辑涂药。消毒脊柱稳定。 ANESthetize鼠标采用腹腔氯胺酮/甲苯​​噻嗪（100毫克/ 10毫克/公斤）的鸡尾酒。从鼠标的脖子剃了头发。 </li><li>皮肤清洁后用聚维酮碘溶液和70％的酒精，将鼠标移动一个加热垫加热走上手术台。包括动物的眼睛眼药膏，以防止角膜干燥。 </li><li>麻醉诱导后（达到当鼠标不响应的尾巴捏），使颈后正中皮肤切口从枕部皮下脂肪垫下颈椎。在放大倍率，执行正中切口，在C2之间的斜方肌和分裂半棘头癣肌肉。肌下脂肪垫的鉴定有利于正确层的夹层。 </li><li>中线肌肉解剖尾端延伸到T2棘突作为一个可靠的地标。剪切连接到T2椎骨的肌肉和移除软骨部为T2棘突。 </li><li>通过使用微型剪刀的一对T2薄层解剖从C2椎旁的肌肉。肌肉开始清扫相邻棘突及双侧小关节延伸。分开紧靠棘突和薄片（在骨膜层），以减少出血的肌肉。横向切面暴露后，将鼠标放在U形通道的LISA阶段。 </li><li>将不锈钢臂下方的暴露双边层面。武器一旦到位，拧紧拇指螺丝钢臂固定脊柱。保持坚定的目标椎固定，并提供了极好的曝光。臂可以进行调整，以提供精确的水平方向的脊柱。 </li><li>切开C5和C6之间的黄韧带，揭露相关硬膜。之间的层间空间，使用30 G针，创建一个小的durotomy通过它被放置microscissors延长durotomy。脊髓现正准备接受控制裂伤病变。 </li></ol> 2。颈椎脊髓裂伤使用LISA设备的<ol><li>颈椎脊髓膨大的宽度变化在不同层面。于C5-6采用了2.3毫米的平刃背侧半切病变的设置的振动的振幅，以覆盖整个宽度的脊髓。叶片获得精细的科学工具公司（福斯特市，CA），并修改为脊髓挫裂伤。维持在≥0.5毫米刀片振荡的振幅较低的振幅电平会削弱便于编码裂伤。 </li><li>脊柱定位稳定剂和鼠标的LISA阶段。该刀片被安装到LISA，其位置控制的微驱动器能够运动的三个范围。 图1中描述的激光干涉仪的组件和它们的功能。 </li><li>功率叶片振动开关。根据MAGNIFication，移动鼠标，使暴露的脊髓下方的振动叶片直接定位。 </li><li>支持鼠标对振荡片提升阶段。 “0”的位置被记录下来，当刀片勉强触及脊髓背静脉。测量的深度相对于“0”的位置的脊髓裂伤。 </li><li>舞台上的地位提升微驱动控制：一个微驱动器旋钮转360°0.25毫米提升阶段。因此，0.75毫米背半切损伤是由微驱动器旋钮转动3次。病变部位的准确度是±0.01毫米。当叶片开始以划破的脊髓，润滑用生理盐水冲洗手术野。脊髓的切削深度控制由垂直微驱动器是独立的视觉指导。 </li><li>一旦已达到预定深度时，转动振动开关。在理想的情况下，振荡刀片定位在升esion组织变形没有证据的差距。下阶段从切刀和使用棉花棉签清除血液和生理盐水从手术领域。止血自发地发生在&lt;1分钟。 </li><li>松开鼠标脊柱稳定。约椎旁肌用6-0丝线缝合关闭皮肤伤口使用不锈钢米歇尔剪辑。 </li></ol> 3。动物护理<ol><li>皮下注入1-2毫升生理盐水共恢复知觉时保持足够的水化和鼠标放置在一个加热垫的回收笼。 </li><li>提供水和软食品即兴和管理48小时手术后的止痛药。有没有必要背的脊髓半切后膀胱护理。 </li></ol>

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<ol><li>几位作者（YPZ，XMX，CBS）在路易斯维尔撞击系统公司的财务权益</li><li>的作者，张忆萍，丽莎盾牌，克里斯托弗B.盾牌，诺顿医疗保健，路易斯维尔，肯塔基州的雇员。采用其他作者，印第安纳波利斯，印第安纳大学。 </li><li>作者没有收到任何公司生产在这篇文章中使用的试剂或仪器的资金。 </li></ol>

椎稳定裂伤伤害到脊髓前已经获得棘突固定。颈椎前凸曲线和夹具附件易碎短颈椎棘突从C3通过T1鼠标防止有效的脊柱稳定。此外，使用刀片或microscissors用于在手动控制下，会导致显着的组织变形创建病变6的深度的可变性。这可能导致的误译数据，尤其是在轴突再生的具体途径研究。例如，备用背皮质轴突可能被误解为再生轴突，如果背皮质脊髓是没有完全横断的时间之破坏。这些挑战是可以克服的脊柱稳定装置通过使用固定在一个单一的水平和精确之破坏的脊髓的各个。此外，使用啊IGH频率振荡片产生了尖锐的破碎或相邻脊髓挫伤，裂伤无。该方法已被用于生产脊髓裂伤损伤的大鼠9,12,14，与后续的修改，以产生胸髓撕裂老鼠6。在目前的通信中，我们描述了在鼠标的创建可靠的宫颈裂伤病变的方法。 就脊髓前后径&lt;2毫米，鼠标，精确的深度的裂伤病变的建立了可靠的实验模型至关重要。最小的变性病变的深度将显着改变轴突再生以及体积和行为研究的实验评估的结果。的损伤深度，使用这种方法的准确度为±0.01毫米，因为我们使用高精密微驱动程序来控制所述切割刀片的位置。此方法减少了不一致的情况其他模型中创建一个裂伤SCI相干。这种方法是特别有用的研究轴突再生的长的通路脊髓位于脊髓背半部，如皮质脊髓束，红核脊髓束和背侧升序道。使用这种方法，这些纤维束可以完全可靠地横切。在这方面，数据的解释的错误被最小化，从而提高对SCI的实验研究报告的可靠性。 综上所述，我们已经描述了一种新的技术来创建一个可重复的脊髓型颈椎病裂伤损伤在鼠标体内模型。这种技术是基于对脊柱稳定的颈的侧面和裂伤的脊髓使用振动叶片固定。使用这种方法在6老鼠背部的胸椎脊髓裂伤模型中，我们表明裂伤深度，组织学和紧之间的相关性行为恢复。这样的技术也被认为是可靠的由多个其它实验室2,12。

转基因小鼠的可用性是一个功能强大的工具来识别特定基因发挥作用机制SCI影响。裂伤SCI是一个重要的模型，用来研究治疗药物或分子可能提供有效的治疗，这次受伤后8。由于难以把握参与维持脊柱内固定5,11薄和脆弱的棘突固定在创建过程中裂伤损伤小鼠棘突是不精确。仅为0.2毫米（直径的10％的小鼠脊髓）的裂伤的深度的可变性导致的数据的误导性的解释。的性质和程度的脊髓裂伤病变的，必须精确地定义10。为了应对这一挑战，我们已经开发出一种新技术，由椎稳定，并使用连接到路易斯维尔损伤系统装置的制造叶片（LISA）产生一个裂伤SCI 7,14。这种伤害是由使用一个大幅振荡的刀片，避免组织裂伤过程中变形。裂伤的深度是通过使用微驱动控制裂伤深度为0.01毫米的精度精确。切割刀片是定制的，以特定的形状和宽度，以创建所需的裂伤轮廓9。我们证明1）的方法，颈椎曝光，2）椎稳定的技术，使用双侧小关节固定装置，以及3）创建一个的宫颈裂伤损伤的使用振动叶片。

<table border="1">
 <tbody>
 <tr>
 <td>Name of Reagent/Material</td>
 <td>Company</td>
 <td>Catalogue Number</td>
 <td>Comments</td>
 </tr>
 <tr>
 <td>Mice vertebral stabilizer </td>
 <td>Louisville Impactor System</td>
 <td></td>
 <td>Stabilize and expose the cervical vertebra</td>
 </tr>
 <tr>
 <td>LISA vibraknife </td>
 <td>Louisville Impactor System</td>
 <td></td>
 <td>Produce the laceration injury of the cervical spinal cord</td>
 </tr>
 <tr>
 <td>Spring Scissors</td>
 <td>Fine Science Tools (USA) </td>
 <td>15013-12</td>
 <td>Skin and trapezius muscle incision</td>
 </tr>
 <tr>
 <td>Spring Scissors</td>
 <td>Fine Science Tools (USA) </td>
 <td>15023-10</td>
 <td>Separate muscles from the laminae</td>
 </tr>
 <tr>
 <td>Spring Scissors</td>
 <td>Fine Science Tools (USA) </td>
 <td>15002-08</td>
 <td>Incision of dura</td>
 </tr>
 <tr>
 <td>Graefe forceps </td>
 <td>Fine Science Tools (USA) </td>
 <td>11154-10</td>
 <td>Retract skin</td>
 </tr>
 <tr>
 <td>Dumont #7 forceps </td>
 <td>Fine Science Tools (USA) </td>
 <td>11274-20</td>
 <td>Muscle retraction (tip modified)(Fig. A)</td>
 </tr>
 <tr>
 <td>Dumont SS forceps </td>
 <td>Fine Science Tools (USA) </td>
 <td>11203-25</td>
 <td>Fixation of vertebra (tip modified )(Fig.B)</td>
 </tr>
 <tr>
 <td>30G needle </td>
 <td>Becton Dickenson</td>
 <td>305106</td>
 <td>Create a dural opening </td>
 </tr>
 <tr>
 <td>6-0 suture </td>
 <td>Ethicon </td>
 <td>8806H</td>
 <td>Close muscle and fascial layers </td>
 </tr>
 <tr>
 <td>wound clip </td>
 <td>Fine Science Tools (USA) </td>
 <td>12031-07</td>
 <td>Skin closure</td>
 </tr>
 <tr>
 <td>Tribromoethanol (Avertin)</td>
 <td>Sigma-Aldrich</td>
 <td>90710-10G</td>
 <td>Anesthetic agent</td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Louisville Impactor System, Inc, 210 E. Gray St., Suite 1102, Louisville, KY 40202, (502) 629-5510, E-mail: <a href="mailto:cbshields1@gmail.com">cbshields1@gmail.com</a>
 Fine Science Tools (USA), Inc, 373-G Vintage Park Drive, Foster City, CA 94404-1139, (800) 521-2109, E-mail: <a href="mailto:info@finescience.com">info@finescience.com</a> 
 Becton Dickenson, 1 Becton Drive, Franklin Lakes, NJ USA 07417, (201) 847-6800 Ethicon, Route 22 West,
 Somerville, NJ 08876 1-877-ETHICON 
 Sigma-Aldrich Corp. 
 St. Louis, MO, USA, 63178 (314) 771-5765, E-mail: cssorders@sial.com</td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Figure A is the modified Dumont #7 forceps; B is the modified Dumont SS forceps.</td>
 </tr>
 </tbody>
 </table>

controlled cervical laceration injury in mice

利用转基因小鼠增强了我们的一些神经系统疾病，如脊髓损伤（SCI）的分子机制的理解。写意手动控制用于生产裂伤SCI模型创建不一致的受伤往往与暗恋或挫伤成分，因此，开发一种新技术。结合1）颈椎稳定椎小关节固定，2）增强脊髓暴露宫颈裂伤SCI我们的模型用写意的方法解决了固有的困难，3）建立一个可重复使用的脊髓裂伤的振荡片精确度为±0.01毫米的深度，而不相关的挫伤。如徒手使用手术刀或剪刀的创建SCI裂伤的标准方法相比，本方法已经产生了一致的病变。这种方法是非常有用的研究轴突再生corticosp原稿，红核脊髓和背上升大片。

固定目标椎生成精确小鼠脊髓病变是极为重要的。我们的脊柱稳定装置克服的解剖短鼠标颈椎棘突和腹部前凸的问题。颈椎暴露我们的颈椎稳定（ 图2）。我们的鼠标脊椎稳定装置是一个可靠的技术准备脊柱脊髓型颈椎程序。使用LISA病变部位的深度是精确到0.01毫米6,13。精确的裂伤导致没有挫伤上面的病变/组织界面（ 图3）。 C57BL / 6小鼠背侧半切病灶的精确度表现在，在一项研究中，0.9毫米深的裂伤延长只是超出了中央管在每个标本病理切片证实脊髓1轴突再生。所有这些动物的运动恢复编后这脊髓裂伤损伤。 <img alt="图1" src="/files/ftp_upload/50030/50030fig1.jpg" /> 图1（A）鼠标在脊柱稳定放在LISA阶段。上述振动叶片朝向撕裂的脊髓。微驱动器的控件都位于舞台下方，设计定位鼠标，在适当的地点。垂直的微驱动器控制病变的深度和倾斜旋钮控制脊髓的水平面上，以防止成角的裂伤。开关控制振动电机，另一个旋钮调节的幅度。（B）0.75毫米背半切裂伤病变切割完整的层拱门之下。 <img alt="图2" src="/files/ftp_upload/50030/50030fig2.jpg" /> 图2。 </st荣&gt;（A）鼠标的脊柱稳定剂组成的U形通道和两个手臂和连接器。鼠标被放置在C槽用于颈椎脊髓损伤，胸脊髓损伤的T槽（B）颈椎被固定放置武器下的横向切面，然后锁定拇指螺丝。硬脑膜暴露薄层C5-6，C6-7，和C7-T1之间没有任何清除骨。 <img alt="图3" src="/files/ftp_upload/50030/50030fig3.jpg" /> 图3。四脊髓背角撕裂，在深度为0.5，0.8，1.1，和1.4毫米，在矢状视图（甲酚紫和曙红染色）观察描绘了高的精确度，使用这种技术。

Watch this Scientific Journal Video about Controlled Cervical Laceration Injury in Mice at JoVE.com

Controlled Cervical Laceration Injury in Mice

一种新型的技术来创建一个可重复的<em&gt;在体内</em&gt;脊髓型颈椎病在鼠标裂伤损伤模型。这种技术是基于对脊柱稳定固定的颈的侧面和使用的摆动刀片的精确度为±0.01 mm的脊髓裂伤。

控制宫颈裂伤损伤小鼠

Use of genetically modified mice enhances our  understanding of molecular mechanisms underlying several neurological disorders  such as a spinal cord ...

controlled-cervical-laceration-injury-in-mice

Research

JoVE Journal

Medicine

16.4K 次观看.  Norton Healthcare. 一种新型的技术来创建一个可重复的在体内脊髓型颈椎病在鼠标裂伤损伤模型。这种技术是基于对脊柱稳定固定的颈的侧面和使用的摆动刀片的精确度为±0.01 mm的脊髓裂伤。

视频: Controlled Cervical Laceration Injury in Mice

Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exchange (36). We have developed a murine model of ALI by using a pressure-controlled ventilation to induce ventilator-induced lung injury (2). For this purpose, C57BL/6 mice are anesthetized and a tracheotomy is performed followed by induction of ALI via mechanical ventilation. Mice are ventilated in a pressure-controlled setting with an inspiratory peak pressure of 45 mbar over 1 - 3 hours. As outcome parameters, pulmonary edema (wet-to-dry ratio), bronchoalveolar fluid albumin content, bronchoalveolar fluid and pulmonary tissue myeloperoxidase content and pulmonary gas exchange are assessed (2). Using this technique we could show that it sufficiently induces acute lung inflammation and can distinguish between different treatment groups or genotypes (1-3, 5). Therefore this technique may be helpful for researchers who pursue molecular mechanisms involved in ALI using a genetic approach in mice with gene-targeted deletion.

A murine model for ventilator induced lung injury is an important tool to study an acute lung injury in vivo. Here, we report an easy applicable in situ model for acute lung injury using high-pressure mechanical ventilation to induce acute failure of the lung.

压力控制通气诱导小鼠急性肺损伤

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged ...

科研

医学

Intraspinal Cell Transplantation for Targeting Cervical Ventral Horn in Amyotrophic Lateral Sclerosis and Traumatic Spinal Cord Injury

Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) cases 1 and is the ultimate cause of death in patients with the motor neuron disorder, amyotrophic laterals sclerosis (ALS) 2.
ALS is a devastating neurological disorder that is characterized by relatively rapid degeneration of upper and lower motor neurons. Patients ultimately succumb to the disease on average 2-5 years following diagnosis because of respiratory paralysis due to loss of phrenic motor neuron innnervation of the diaphragm 3. The vast majority of cases are sporadic, while 10% are of the familial form. Approximately twenty percent of familial cases are linked to various point mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene on chromosome 21 4. Transgenic mice 4,5 and rats 6 carrying mutant human SOD1 genes (G93A, G37R, G86R, G85R) have been generated, and, despite the existence of other animal models of motor neuron loss, are currently the most highly used models of the disease.
Spinal cord injury (SCI) is a heterogeneous set of conditions resulting from physical trauma to the spinal cord, with functional outcome varying according to the type, location and severity of the injury 7. Nevertheless, approximately half of human SCI cases affect cervical regions, resulting in debilitating respiratory dysfunction due to phrenic motor neuron loss and injury to descending bulbospinal respiratory axons 1. A number of animal models of SCI have been developed, with the most commonly used and clinically-relevant being the contusion 8.
Transplantation of various classes of neural precursor cells (NPCs) is a promising therapeutic strategy for treatment of traumatic CNS injuries and neurodegeneration, including ALS and SCI, because of the ability to replace lost or dysfunctional CNS cell types, provide neuroprotection, and deliver gene factors of interest 9.
Animal models of both ALS and SCI can model many clinically-relevant aspects of these diseases, including phrenic motor neuron loss and consequent respiratory compromise 10,11. In order to evaluate the efficacy of NPC-based strategies on respiratory function in these animal models of ALS and SCI, cellular interventions must be specifically directed to regions containing therapeutically relevant targets such as phrenic motor neurons. We provide a detailed protocol for multi-segmental, intraspinal transplantation of NPCs into the cervical spinal cord ventral gray matter of neurodegenerative models such as SOD1G93A mice and rats, as well as spinal cord injured rats and mice 11.

Neural precursor transplantation is a promising strategy for protecting and/or replacing lost/dysfunctional cervical phrenic motor neurons in spinal cord injury (SCI) and the motor neuron disorder, amyotrophic laterals sclerosis (ALS). We provide a protocol for cell delivery to cervical spinal cord ventral horn in rodent models of ALS and SCI.

椎管内针对肌萎缩性脊髓侧索硬化症和外伤性脊髓损伤颈腹角细胞移植

Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) ...

A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of spinal cord injury (SCI) in which the thoracic spinal cord is injured. Additionally, because most human cord injuries occur as the result of blunt, non-penetrating trauma (e.g. motor vehicle accident, sporting injury) where the spinal cord is violently struck by displaced bone or soft tissues, the majority of SCI researchers are of the opinion that the most clinically relevant injury models are those in which the spinal cord is rapidly contused.1 Therefore, an important step in the preclinical evaluation of novel treatments on their way to human translation is an assessment of their efficacy in a model of contusion SCI within the cervical spinal cord. Here, we describe the technical aspects and resultant anatomical and behavioral outcomes of an unilateral contusive model of cervical SCI that employs the Infinite Horizon spinal cord injury impactor.
Sprague Dawley rats underwent a left-sided unilateral laminectomy at C5. To optimize the reproducibility of the biomechanical, functional, and histological outcomes of the injury model, we contused the spinal cords using an impact force of 150 kdyn, an impact trajectory of 22.5&deg; (animals rotated at 22.5&deg;), and an impact location off of midline of 1.4 mm. Functional recovery was assessed using the cylinder rearing test, horizontal ladder test, grooming test and modified Montoya's staircase test for up to 6 weeks, after which the spinal cords were evaluated histologically for white and grey matter sparing.
The injury model presented here imparts consistent and reproducible biomechanical forces to the spinal cord, an important feature of any experimental SCI model. This results in discrete histological damage to the lateral half of the spinal cord which is largely contained to the ipsilateral side of injury. The injury is well tolerated by the animals, but does result in functional deficits of the forelimb that are significant and sustained in the weeks following injury. The cervical unilateral injury model presented here may be a resource to researchers who wish to evaluate potentially promising therapies prior to human translation.

A reliable and repeatable way to produce a cervical unilateral spinal cord injury using the Infinite Horizon impactor is described. The method takes advantage of a custom designed frame and clamp to stabilize the spine. The standardized procedure and biomechanical injury parameters result in sufficient and sustained injuries.

单侧颈脊髓损伤的挫伤模型，利用无限的地平线冲击

While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of ...

Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice

Ischemia-reperfusion induced acute kidney injury (IR-AKI) is widely used as a model of AKI in mice, but results are often quite variable with high, often unreported mortality rates that may confound analyses. Bilateral renal pedicle clamping is commonly used to induce IR-AKI, but differences between effective clamp pressures and/or renal responses to ischemia between kidneys often lead to more variable results. In addition, shorter clamp times are known to induce more variable tubular injury, and while mice undergoing bilateral injury with longer clamp times develop more consistent tubular injury, they often die within the first 3 days after injury due to severe renal insufficiency. To improve post-injury survival and obtain more consistent and predictable results, we have developed two models of unilateral ischemia-reperfusion injury followed by contralateral nephrectomy. Both surgeries are performed using a dorsal approach, reducing surgical stress resulting from ventral laparotomy, commonly used for mouse IR-AKI surgeries. For induction of moderate injury BALB/c mice undergo unilateral clamping of the renal pedicle for 26 min and also undergo simultaneous contralateral nephrectomy. Using this approach, 50-60% of mice develop moderate AKI 24 hr after injury but 90-100% of mice survive. To induce more severe AKI, BALB/c mice undergo renal pedicle clamping for 30 min followed by contralateral nephrectomy 8 days after injury. This allows functional assessment of renal recovery after injury with 90-100% survival. Early post-injury tubular damage as well as post injury fibrosis are highly consistent using this model.

We describe models of moderate and severe ischemia-reperfusion-induced kidney injury in which the mice undergo unilateral renal pedicle clamping followed by simultaneous or delayed contralateral nephrectomy, respectively. These models consistently give rise to renal dysfunction and post-injury fibrosis, but injury severity and survival are dependent on mouse background, age and surgical equipment.

急性肾损伤和伤后纤维化小鼠缺血再灌注模型

Ischemia-reperfusion induced acute kidney injury (IR-AKI) is widely used as a model of AKI in mice, but results are often quite variable with high, often ...

A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity

A cervical spinal cord injury induces permanent paralysis, and often leads to respiratory distress. To date, no efficient therapeutics have been developed to improve/ameliorate the respiratory failure following high cervical spinal cord injury (SCI). Here we propose a murine pre-clinical model of high SCI at the cervical 2 (C2) metameric level to study diverse post-lesional respiratory neuroplasticity. The technique consists of a surgical partial injury at the C2 level, which will induce a hemiparalysis of the diaphragm due to a deafferentation of the phrenic motoneurons from the respiratory centers located in the brainstem. The contralateral side of the injury remains intact and allows the animal recovery. Unlike other SCIs which affect the locomotor function (at the thoracic and lumbar level), the respiratory function does not require animal motivation and the quantification of the deficit/recovery can be easily performed (diaphragm and phrenic nerve recordings, whole body ventilation). This pre-clinical C2 SCI model is a powerful, useful, and reliable pre-clinical model to study various respiratory and non-respiratory neuroplasticity events at different levels (molecular to physiology) and to test diverse putative therapeutic strategies which might improve the respiration in SCI patients.

Respiratory failure is the leading cause of death following a cervical spinal cord injury. Having a reproducible, quantifiable, and reliable pre-clinical animal model of respiratory failure induced by a partial cervical injury will help to understand the subsequent respiratory and non-respiratory neuroplasticity and allow testing putative repair strategies.

颈脊髓损伤的小鼠模型研究后皮损呼吸神经可塑性

A cervical spinal cord injury induces permanent paralysis, and often leads to respiratory distress. To date, no efficient therapeutics have been developed ...

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.

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, ...

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury

Spinal cord injuries (SCI) cause serious neurological impairment and psychological, economic, and social consequences for patients and their families. Clinically, more than 50% of SCI affect the cervical spine1. As a consequence of the primary injury, a cascade of secondary mechanisms including inflammation, apoptosis, and demyelination occur finally leading to tissue scarring and development of intramedullary cavities2,3. Both represent physical and chemical barriers to cell transplantation, integration, and regeneration. Therefore, shaping the inhibitory environment and bridging cavities to create a supportive milieu for cell transplantation and regeneration is a promising therapeutic target4. Here, a contusion/compression model of cervical SCI using an aneurysm clip is described. This model is more clinically relevant than other experimental models, since complete transection or ruptures of the cord are rare. Also in comparison to the weight drop model, which in particular damage the dorsum columns, circumferential compression of the spinal cord appears advantageous. Clip closing force and duration can be adjusted to achieve different injury severity. A ring spring facilitates precise calibration and constancy of clip force. Under physiological conditions, synthetic self-assembling peptides (SAP) self-assemble into nanofibers and thus, are appealing for application in SCI5. They can be injected directly into the lesion minimizing damage to the cord. SAPs are biocompatible structures erecting scaffolds to bridge intramedullary cavities and thus, equip the damaged cord for regenerative treatments. K2(QL)6K2 (QL6) is a novel SAP introduced by Dong et al.6 In comparison to other peptides, QL6 self-assembles into &#946;-sheets at neutral pH6.14 days after SCI, after the acute stage, SAPs are injected into the center of the lesion and neural precursor cells (NPC) are injected into adjacent dorsal columns. In order to support cell survival, transplantation is combined with continuous subdural administration of growth factors by osmotic micro pumps for 7 days.

Treating cervical spinal cord injury with both self-assembling peptides (SAP) and neural precursor cells (NPC), together with growth factors, is a promising approach to promote regeneration and recovery. A contusion/compression aneurysm clip rat model of cervical SCI and combined treatment involving SAP injection and NPC transplantation is established.

在实验颈脊髓损伤协同使用神经前体细胞，并自组装肽的

Spinal cord injuries (SCI) cause serious neurological impairment and psychological, economic, and social consequences for patients and their families. ...

Heterotopic Cervical Heart Transplantation in Mice

The heterotopic cervical heart transplantation in mice is a valuable tool in transplant and cardiovascular research. The cuff technique greatly simplifies this model by avoiding challenging suture anastomoses of small vessels thereby reducing warm ischemia time. In comparison to abdominal graft implantation the cervical model is less invasive and the implanted graft is easily accessible for further follow-up examinations. Anastomoses are performed by pulling the ascending aorta of the graft over the cuff with the recipient&#8217;s common carotid artery and by pulling the main pulmonary artery over the cuff with the external jugular vein. Selection of appropriate cuff size and complete mobilization of the vessels are important for successful revascularization. Ischemia-reperfusion (I/R) injury can be minimized by perfusing the graft with a cardioplegic solution and by hypothermia. In this article, we provide technical details for a simplified and improved cuff technique, which should allow surgeons with basic microsurgical skills to perform the procedure with a high success rate.

The cuff technique shortens and facilitates the model of heterotopic cervical heart transplantation in mice by avoiding technically challenging suture anastomoses of small vessels. The technical details shown in this video paper should allow researches to establish this model in their laboratories.

颈椎异位心脏移植小鼠

The heterotopic cervical heart transplantation in mice is a valuable tool in transplant and cardiovascular research. The cuff technique greatly simplifies ...

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 ...

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. ...