审裁处已收到来自中医药大学哥廷根Forschungsförderungsprogramm的资金支持。 PL和MB分别由东风集团的大脑（郊野公园及海岸公园委员会），哥廷根大学分子生理学研究中心的支持。作者感谢录像和比吉特Liebau的援助，音频和视频编辑的帮助医生拉尔斯Tatenhorst。

动物购自杰克逊实验室（＃002726）1。他们在临床上得分和遭受的运动功能（旋转试验），肌力（悬丝试验）测试。所有这些测试，并以准备脊髓后杀害动物已按照非常接近当地的指引适当进行动物实验。 1。临床评分除了 ​​体重小鼠的评估检查以下4点计分制2电机赤字的迹象： 4分：正常（无运动功能障碍的迹象） 3点：后肢震颤是显而易见的，当尾巴暂停 2分：步态异常是目前 1点：至少有一个后肢拖 0点：对称瘫痪，不能以自己的权利或损失最大体重的20％;在这种情况下，立即安乐死动物实验终止 2。运动功能和肌肉力量的测试吊线这个测试是用来评估肌力3，4。所有的动物进行旋转试验后，至少有一至两天的测试。每个鼠标被放置在一个0.8厘米的间隔定制丝盖和谨慎天翻地覆，60厘米以上的稻草覆盖的底部。经过培训至少180秒连续三次下降的延迟测量。每个鼠标三次尝试举行倒盖一个180秒的最高和最长记录。 旋转试验3，4。良好的性能，需要高度的感觉协调。本机应放置在一个平静和非令人不安的环境，以避免对试验动物的牵张刺激。它由计算机控制的电动机驱动旋转主轴和五鼠五车道。小鼠的瀑布是在底部的塑料板自动检测压力。培训后连续三年至少有180秒的时间，在15转的时间，动物可以保持旋转杆的恒定速度进行了测量。每个动物都经历了三个试验和最长潜伏期，没有下降记录。被选为截止时间180秒的时间，在这段时间内检测，因为大多数的动作协调性的显着性差异。 3。脊髓制备<ol class="lalpha"><li>动物被杀害的CO 2气腹，根据当地的指引立即transcardially灌注4％多聚甲醛溶液PBS溶液。 </li><li>为了准备牺牲鼠标的脊髓，动物被放置到一个操作表和四肢上侧固定，为了揭露鼠标的背面。 </li><li>一个短洗了70％的乙醇溶液清洗清扫现场，平坦的被毛。 </li><li>用锋利的手术刀在中线皮肤切开。为了方便切割皮肤向两侧伸展。如果腿部肌肉应做好准备，他们的皮肤也被切开。 </li><li>皮肤切口完成后，被拉到一边，一个镊子，暴露身体的底层浅筋膜。 </li><li>颈部肌肉和颈部韧带被删除，是CArefully准备。要小心，不要切开深入病灶脊髓。肩膀肌肉也可以被删除，以便更好地暴露脊柱。 </li><li>然后从整个脊柱椎旁肌。 </li><li>为了打开脊柱几个laminectomies必须执行。每个人都应该从颅上的部分，在寰枕关节部位。 </li><li>这是最简单的删除上两肢固定和量力的颈部，能够更好地执行第一腰椎椎板。这些被拉走，而不触及暴露的脊髓型颈椎病。 </li><li>更多的椎骨被删除第一横断直角剪刀两侧椎拱门，然后拉背进程。应删除余下的椎骨的侧部，便于以后的脊髓完全去除。 </li><li>腰脊柱的解剖标志升线是在颈髓，这也是目前的肿大。 </li><li>说完整个脊髓椎板，确保你也横切所有腹侧根和释放脑膜脊髓硬膜。 </li><li>然后颅颈脊髓被切断，你开始清除脊髓。 </li><li>最后在远端马尾，马尾也切断脊髓完全释放。 </li><li>最终，脊髓被放置到postfixating解决方案（如4％多聚甲醛）过夜，并可以进一步处理。我们通常冰冻切片脊髓免疫组织化学分析准备。 </li></ol> 4。代表结果脊髓制备技术代表本视频文章的重点。这是一个必不可少的先决条件，为以后的组织切片和免疫组化分析，最终为脊柱升线部分。作为最终结果的一个例子，鼠标的前角区域的鼠标一个野生的脊柱脊髓腰（WT）和免疫组化的SOD G93A转基因（TG）相关检验证明。运动神经元，可确定一个主抗胆碱抗体和随后的次要Cy3标记抗体荧光标记。此外，用DAPI（4,6-diamidino-2-苯基）核反污渍已完成（ 图1）。 <img src="/files/ftp_upload/3936/3936fig1.jpg" alt="图1" /> 可视化与抗胆碱抗体（红色）和反染色细胞的细胞核用DAPI（蓝色）的野生型（WT）鼠标腰脊髓前角（左）和运动神经元的免疫检测的荧光显微图1。 G93A转基因是一种SOD（TG）（右）在130天的年龄鼠标。比例尺：40微米。 由于免疫组化分析G93A小鼠的超氧化物歧化酶是不是这篇文章的主要范围，请咨询原始出版物在这些转基因小鼠已特点和治疗方法的研究进一步参考文献1，5，6最近的。如果治疗效果，应区分明确了免疫组化水平定量评估算法应适用于支持由体视软件（例如见7）。

<ol>
	<li>Gurney, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+neuron+degeneration+in+mice+that+express+a+human+Cu,+Zn+superoxide+dismutase+mutation.">Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation.</a> Science. 264 (5166), 1772-1775 (1994).</li><li>Weydt, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessing+disease+onset+and+progression+in+the+SOD1+mouse+model+of+ALS.">Assessing disease onset and progression in the SOD1 mouse model of ALS.</a> Neuroreport. 14 (7), 1051-1054 (2003).</li><li>Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+phenotyping+strategies+for+mutant+mice.">Behavioral phenotyping strategies for mutant mice.</a> Neuron. 57 (6), 809-818 (2008).</li><li>Miana-Mena, F. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimal+methods+to+characterize+the+G93A+mouse+model+of+ALS.">Optimal methods to characterize the G93A mouse model of ALS.</a> Amyotroph. Lateral Scler. Other Motor Neuron Disord. 6 (1), 55-62 (2005).</li><li>Zhong, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Activated+protein+C+therapy+slows+ALS&#45;like+disease+in+mice+by+transcriptionally+inhibiting+SOD1+in+motor+neurons+and+microglia+cells.">Activated protein C therapy slows ALS&#45;like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells.</a> J. Clin. Invest. 119 (11), 3437-3449 (2009).</li><li>Pitzer, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Granulocyte&#45;colony+stimulating+factor+improves+outcome+in+a+mouse+model+of+amyotrophic+lateral+sclerosis.">Granulocyte&#45;colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis.</a> Brain. 131 (Pt. 12), 3335-3347 (2008).</li><li>Gowing, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ablation+of+proliferating+microglia+does+not+affect+motor+neuron+degeneration+in+amyotrophic+lateral+sclerosis+caused+by+mutant+superoxide+dismutase.">Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase.</a> J. Neurosci. 28 (41), 10234-10244 (2008).</li><li>Scott, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=interpretation+of+studies+in+the+standard+murine+model+of+ALS.">interpretation of studies in the standard murine model of ALS.</a> Amyotroph Lateral Scler. 9 (1), 4-15 (2008).</li><li>Turner, B. J., Talbot, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transgenics,+toxicity+and+therapeutics+in+rodent+models+of+mutant+SOD1&#45;mediated+familial+ALS.">Transgenics, toxicity and therapeutics in rodent models of mutant SOD1&#45;mediated familial ALS.</a> Prog Neurobiol. 85 (1), 94-134 (2008).</li><li>Corse, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preclinical+testing+of+neuroprotective+neurotrophic+factors+in+a+model+of+chronic+motor+neuron+degeneration.">Preclinical testing of neuroprotective neurotrophic factors in a model of chronic motor neuron degeneration.</a> Neurobiol Dis. 6 (5), 335-346 (1999).</li><li>Knippenberg, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Significance+of+behavioural+tests+in+a+transgenic+mouse+model+of+amyotrophic+lateral+sclerosis+&#40;ALS&#41;.">Significance of behavioural tests in a transgenic mouse model of amyotrophic lateral sclerosis &#40;ALS&#41;.</a> Behav Brain Res. 213 (1), 82-87 (2010).</li><li>Burgess, R. W., Cox, G. A., Seburn, K. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuromuscular+disease+models+and+analysis.">Neuromuscular disease models and analysis.</a> Methods Mol. Biol. 602, 347-393 (2010).</li><li>Hayworth, C. R., Gonzalez-Lima, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pre-symptomatic+detection+of+chronic+motor+deficits+and+genotype+prediction+in+congenic+B6.SOD1(G93A)+ALS+mouse+model.">Pre-symptomatic detection of chronic motor deficits and genotype prediction in congenic B6.SOD1(G93A) ALS mouse model.</a> Neuroscience. 164 (3), 975-985 (2009).</li><li>Ludolph, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+preclinical+animal+research+in+ALS&#47;MND:+A+consensus+meeting.">Guidelines for preclinical animal research in ALS&#47;MND: A consensus meeting.</a> Amyotroph Lateral Scler. 11 (1-2), 38-45 (2010).</li><li>Boillee, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Onset+and+progression+in+inherited+ALS+determined+by+motor+neurons+and+microglia.">Onset and progression in inherited ALS determined by motor neurons and microglia.</a> Science. 5778 (3), 1389-1392 (2006).</li></ol>

没有利益冲突的声明。

的SOD1（G93A）基因小鼠模型是一个有价值的动物模型，研究病程渐进的运动神经元的损失相比，人类肌萎缩性侧索硬化症8。在这个模型中，各种不同的治疗模式已被评估，并表示以后在人类的临床研究8-10测试的基础上。为了能够检测这些小鼠的实验治疗研究中的显着性差异，这是著名的重要性，包括至少24产仔匹配的性别平衡相同的遗传背景的小鼠和遵循双盲设计8。媲美...

<table border="1"><tbody><tr><td></td><td> 生产厂家 </td><td> 订购信息 </td></tr><tr><td> 行为测试 </td><td></td><td></td></tr><tr><td>对小鼠的旋转杆</td><td>乌戈·巴西莱，Comerio，意大利</td><td> ＃47600 </td></tr><tr><td>吊线装置</td><td>定制</td><td></td></tr><tr><td colspan="3"></td></tr><tr><td> 脊髓制备 </td><td></td><td></td></tr><tr><td>操作表 操作灯 防护手套</td><td></td><td></td></tr><tr><td> “鸢尾花”剪刀，到另一边的角度</td><td>精细的科学工具，德国海德堡</td><td> 14063-09 </td></tr><tr><td>科恩的Vannas弹簧剪刀，直</td><td>精细的科学工具，德国海德堡</td><td> 15000-10 </td&gt; </tr><tr><td>微型镊子</td><td> hammacher，索林根，德国</td><td> HWC 111-10 </td></tr><tr><td>手术刀“präzisa加” </td><td> dahlhausen，科隆，德国</td><td> 11.000.00.510，图10 </td></tr></tbody></table>

clinical testing and spinal cord removal in a mouse model for amyotrophic lateral sclerosis (als)

肌萎缩性脊髓侧索硬化症（ALS）是一种致命的神经退行性疾病导致运动神经元逐渐退化。零星的疾病，约50多年的家族性疾病的发病高峰是60岁。由于它的前进方向，50％的患者症状发作后30个月内死亡。为了评估这种疾病的新型治疗方案，基于对人类家族中的超氧化物歧化酶基因突变的SOD1（G93A）突变，如ALS的遗传小鼠模型已产生。最重要的方面，必须评估模型是整体存活率，临床过程和运动功能。在这里，我们证明了临床评价，显示两种行为的电机测试的传导，并提供所有参数的定量评分系统。因为在ALS小鼠模型的深入分析，通常需要的脊髓免疫组化检查，我们展示了其应用做准备详细RSAL椎板方法。模范病理结果证实。 ALS小鼠模型的研究中描绘的检查方法的综合应用，将使研究人员能够可靠地测试未来的治疗方案，它可以提供一个为以后的人体临床试验的基础上。

Watch this Scientific Journal Video about Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis ALS at JoVE.com

Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis ALS

一个肌萎缩性侧索硬化症（ALS）的小鼠模型研究，临床和行为。作为一个伴随的免疫组织化学分析的前提下编制的脊髓详细描述。

临床试验和脊髓去除在肌萎缩性侧索硬化症的小鼠模型（ALS）

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in progressive degeneration of motoneurons. Peak of onset is around 60 ...

clinical-testing-spinal-cord-removal-mouse-model-for-amyotrophic

Research

JoVE Journal

Medicine

Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis (ALS)

27.9K 次观看.  University Medicine Göttingen. 一个肌萎缩性侧索硬化症（ALS）的小鼠模型研究，临床和行为。作为一个伴随的免疫组织化学分析的前提下编制的脊髓详细描述。

视频: Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis ALS

A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis (ALS)

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression across speech subsystems, and for addressing the critical need for sensitive outcome measures for ongoing experimental treatment trials. To address this need, we are obtaining longitudinal profiles of bulbar impairment in 100 individuals based on a comprehensive instrumentation-based assessment that yield objective measures. Using instrumental approaches to quantify speech-related behaviors is very important in a field that has primarily relied on subjective, auditory-perceptual forms of speech assessment1. Our assessment protocol measures performance across all of the speech subsystems, which include respiratory, phonatory (laryngeal), resonatory (velopharyngeal), and articulatory. The articulatory subsystem is divided into the facial components (jaw and lip), and the tongue. Prior research has suggested that each speech subsystem responds differently to neurological diseases such as ALS. The current protocol is designed to test the performance of each speech subsystem as independently from other subsystems as possible. The speech subsystems are evaluated in the context of more global changes to speech performance. These speech system level variables include speaking rate and intelligibility of speech.
The protocol requires specialized instrumentation, and commercial and custom software. The respiratory, phonatory, and resonatory subsystems are evaluated using pressure-flow (aerodynamic) and acoustic methods. The articulatory subsystem is assessed using 3D motion tracking techniques. The objective measures that are used to quantify bulbar impairment have been well established in the speech literature and show sensitivity to changes in bulbar function with disease progression. The result of the assessment is a comprehensive, across-subsystem performance profile for each participant. The profile, when compared to the same measures obtained from healthy controls, is used for diagnostic purposes. Currently, we are testing the sensitivity and specificity of these measures for diagnosis of ALS and for predicting the rate of disease progression. In the long term, the more refined endophenotype of bulbar ALS derived from this work is expected to strengthen future efforts to identify the genetic loci of ALS and improve diagnostic and treatment specificity of the disease as a whole. The objective assessment that is demonstrated in this video may be used to assess a broad range of speech motor impairments, including those related to stroke, traumatic brain injury, multiple sclerosis, and Parkinson disease.

A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis ALS

Objective assessments of the physiological mechanisms that support speech are needed to monitor disease onset and progression in persons with ALS and to quantify treatment effects in clinical trials. In this video, we present a comprehensive, instrumentation-based protocol for quantifying speech motor performance in clinical populations.

延髓功能障碍肌萎缩性脊髓侧索硬化症（ALS）的综合评估议定书

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression ...

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) ...

Acute and Chronic Tactile Sensory Testing after Spinal Cord Injury in Rats

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory testing in rat SCI models is needed. However, until recently, no single testing approach had been validated for SCI so that standardized methods have not been implemented across labs. Additionally, available testing methods could not be implemented acutely or when severe motor impairments existed, preventing studies of the development of SCI-induced allodynia3. Here we present two validated sensory testing methods using von Frey Hair (VFH) monofilaments which quantify changes in tactile sensory thresholds after SCI4-5. One test is the well-established Up-Down test which demonstrates high sensitivity and specificity across different SCI severities when tested chronically5. The other test is a newly-developed dorsal VFH test that can be applied acutely after SCI when allodynia develops, prior to motor recovery4-5. Each VFH monofilament applies a calibrated force when touched to the skin of the hind paw until it bends. In the up-down method, alternating VFHs of higher or lower forces are used on the plantar L5 dermatome to delineate flexor withdrawal thresholds. Successively higher forces are applied until withdrawal occurs then lower force VFHs are used until withdrawal ceases. The tactile threshold reflects the force required to elicit withdrawal in 50% of the stimuli. For the new test, each VFH is applied to the dorsal L5 dermatome of the paw while the rat is supported by the examiner. The VFH stimulation occurs in ascending order of force until at least 2 of 3 applications at a given force produces paw withdrawal. Tactile sensory threshold is the lowest force to elicit withdrawal 66% of the time. Acclimation, testing and scoring procedures are described. Aberrant trials that require a retest and typical trials are defined. Animal use was approved by Ohio State University Animal Care and Use Committee.

We describe two tactile sensory testing methods for acute or chronic periods of spinal cord injury in rats. These validated procedures can detect the development and maintenance of allodynia-like sensations.

在大鼠脊髓损伤后的急性和慢性触觉测试

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory ...

A Contusion Model of Severe Spinal Cord Injury in Rats

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is described to obtain a consistent model of severe SCI. Use of a stereotactic frame and computer controlled impactor allows for creation of reproducible injury. Hypothermia and urinary tract infection pose significant challenges in the post-operative period. Careful monitoring of animals with daily weight recording and bladder expression allows for early detection of post-operative complications. The functional results of this contusion model are equivalent to transection models. The contusion model can be utilized to evaluate the efficacy of both neuroprotective and neuroregenerative approaches.

A contusion model of severe spinal cord injury is described. Detailed pre-operative, operative and post-operative steps are described to obtain a consistent model.

挫伤模型脊髓严重损伤的保护作用

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is ...

Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis

The split hand phenomenon refers to predominant wasting of thenar muscles and is an early and specific feature of amyotrophic lateral sclerosis (ALS). A novel split hand index (SI) was developed to quantify the split hand phenomenon, and its diagnostic utility was assessed in ALS patients. The split hand index was derived by dividing the product of the compound muscle action potential (CMAP) amplitude recorded over the abductor pollicis brevis and first dorsal interosseous muscles by the CMAP amplitude recorded over the abductor digiti minimi muscle. In order to assess the diagnostic utility of the split hand index, ALS patients were prospectively assessed and their results were compared to neuromuscular disorder patients. The split hand index was significantly reduced in ALS when compared to neuromuscular disorder patients (P&#60;0.0001). Limb-onset ALS patients exhibited the greatest reduction in the split&#160;hand index, and a value of 5.2 or less reliably differentiated ALS from other neuromuscular disorders. Consequently, the split&#160;hand index appears to be a novel diagnostic biomarker for ALS, perhaps facilitating an earlier diagnosis.

Dissociated atrophy of intrinsic hand muscles, termed the split hand, appears to be a specific feature of amyotrophic lateral sclerosis (ALS).&#160;Consequently, a novel neurodiagnostic test, termed the split hand&#160;index, was developed to quantify the clinical phenomenon of the split hand, which differentiated ALS from mimic disorders.

在肌萎缩侧索硬化症的诊断游离本质手部肌肉萎缩实用工具

The split hand phenomenon refers to predominant wasting of thenar muscles and is an early and specific feature of amyotrophic lateral sclerosis (ALS). A ...

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, ...

A Radio-telemetric System to Monitor Cardiovascular Function in Rats with Spinal Cord Transection and Embryonic Neural Stem Cell Grafts

High thoracic or cervical spinal cord injury (SCI) can lead to cardiovascular dysfunction. To monitor cardiovascular parameters, we implanted a catheter connected to a radio transmitter into the femoral artery of rats that underwent a T4 spinal cord transection with or without grafting of embryonic brainstem-derived neural stem cells expressing green fluorescent protein. Compared to other methods such as cannula insertion or tail-cuff, telemetry is advantageous to continuously monitor blood pressure and heart rate in freely moving animals. It is also capable of long term multiple data acquisitions. In spinal cord injured rats, basal cardiovascular data under unrestrained condition and autonomic dysreflexia in response to colorectal distension were successfully recorded. In addition, cardiovascular parameters before and after SCI can be compared in the same rat if a transmitter is implanted before a spinal cord transection. One limitation of the described telemetry procedure is that implantation in the femoral artery may influence the blood supply to the ipsilateral hindlimb.

We present a protocol for using a radio-telemetric system to record cardiovascular parameters in T4 spinal cord transected rats eight weeks after embryonic brainstem neural stem cell grafting into the lesion site. Telemetry is an advanced technique to accurately evaluate cardiovascular function in conscious freely moving spinal cord injured rats.

无线电遥测系统，以监测大鼠脊髓横断和胚胎神经干细胞移植在心血管功能

High thoracic or cervical spinal cord injury (SCI) can lead to cardiovascular dysfunction. To monitor cardiovascular parameters, we implanted a catheter ...

Calibrated Forceps Model of Spinal Cord Compression Injury

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The calibrated forceps model of compression injury is a convenient, low cost, and very reproducible animal model for SCI. We used a pair of modified forceps in accordance with the method published by Plemel et al. (2008) to laterally compress the spinal cord to a distance of 0.35 mm. In this video, we will demonstrate a dorsal laminectomy to expose the spinal cord, followed by compression of the spinal cord with the modified forceps. In the video, we will also address issues related to the care of paraplegic laboratory animals. This injury model produces mice that exhibit impairment in sensation, as well as impaired hindlimb locomotor function. Furthermore, this method of injury produces consistent aberrations in the pathology of the SCI, as determined by immunohistochemical methods. After watching this video, viewers should be able to determine the necessary supplies and methods for producing SCI of various severities in the mouse for studies on SCI and/or treatments designed to mitigate impairment after injury.

Spinal cord injury models should be highly reproducible. We demonstrate that the calibrated forceps compression model of spinal cord injury is an easy to use surgical method for generating reproducible injuries to the murine spinal cord.

脊髓压迫损伤的校准钳型

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The ...

A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening protocol, demonstrated in video herein, which reliably assesses the neuromuscular function of SOD1-G93A mice in a quick manner. This protocol encompasses a simple neurological scoring system (NeuroScore) designed to assess hindlimb function. NeuroScore is focused on hindlimb function because hindlimb deficits are the earliest reported neurological sign of disease in SOD1-G93A mice. The protocol developed by ALS TDI provides an unbiased assessment of onset of paresis (slight or partial paralysis), progression and severity of paralysis and it is sensitive enough to identify drug-induced changes in disease progression. In this report, the combination of a detailed manuscript with video minimizes scoring ambiguities and inter-experimenter variability thus allowing for the protocol to be adopted by other laboratories and enabling comparisons between studies taking place at different settings. We believe that this video protocol can serve as an excellent training tool for present and future ALS researchers.

This video protocol describes a sensitive, reliable, and quick method for evaluating the neuromuscular deficits in a transgenic mouse model of amyotrophic lateral sclerosis.

一个快速的表型神经评分系统在ALS的SOD1-G93A小鼠模型评估疾病进展

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening ...

A Neonatal Mouse Spinal Cord Compression Injury Model

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life1, this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques1. Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections1.

This article describes a method for generating a reproducible spinal cord compression injury (SCI) in the neonatal mouse. The model provides an advantageous platform for studying mechanisms of adaptive plasticity that underlie spontaneous functional recovery.

新生儿小鼠脊髓压迫损伤模型

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal ...