我们感谢约翰·韦尔先生和特里Upshall先生为他们的技术专长和援助的摄影和录像。这项工作是通过操作补助JLV从健康研究的加拿大学院和纽芬兰的研究与发展公司和心脏病及中风的加拿大加拿大合作基金会中风回收催化剂赠款的支持。 RBR是基思·格里菲斯纪念心脏及中风基金会研究生奖学金的获得者。

伦理声明:所有实验由纽芬兰的动物保健伦理委员会纪念大学根据加拿大议会关于动物饲养的指导方针批准。 1.小鼠<ol><li>用成年鼠。在这项研究中，成年雄性FVBN小鼠（n = 10）之间2-4个月的被使用。家鼠在12:12小时反向明暗周期，并提供标准啮齿动物食物和水自由采食 。 </li></ol> 2.材料所需圆柱测试<ol><li>获得一台具有透明的顶部拍摄的气瓶检验。表的尺寸是无关紧要的，顶部必须有机玻璃或玻璃，且必须有足够的空间来放置该台下面的反射镜。这允许鼠标从下面录像。使用下表镜子反射通过汽缸的图像。作为替代方案，使用倒置相机（如果可用）。该表在本协议中使用的尺寸为54 x 56×66.5厘米（wxlxh）与51 x 20英寸顶部（WXL）。 </li><li>得到的反射镜。镜子在本协议中所使用的尺寸为34 x58厘米（WXL）。 </li><li>得到透明/有机玻璃筒的鼠标来执行英寸圆柱体在这个协议中使用的尺寸为17.5厘米高，8.8厘米ID，9.5厘米外径与0.35厘米的壁厚。一个更高的汽缸可能需要更积极的小鼠品系。 </li><li>将气缸在桌面和电影在下面的镜面反射。 </li><li>一个摄影机和三脚架是必需的。记录的视频以大约650KB / s，这是每5分钟气缸视频的大约190MB。确保相机具有缩放功能，以确保在气缸涵盖的整个视野​​。 注:在本协议中使用的摄影机是索尼DCR-SR42，40X光学变焦，2000倍数码变焦，680kpix它采用标清，NTSC隔行扫描视频）。 </li><li>获得软件进行分析 - 媒体PL艾尔视频支持，播放速度调节。在这个协议中使用的媒体播放器是VLC媒体播放器V2.1.2。 </li><li>获得的计算机的操作系统能够运行的媒体播放器和监视器的。 </li><li>电子存储的视频是必需的。视频下载到外部硬盘驱动器或将其复制到DVD光盘进行长期存储。 注:在每部影片190MB，84会议将适合在一个16 GB的SD卡和168会议将适合在32GB的SD卡。由于SD介质的相对便宜，并且在一些小鼠中有多少时间需要完成20后轮的不确定性，建议使用32 GB的卡。在目前的研究中，影片是从相机复制到2TB外置硬盘驱动器，然后再复制到DVD作为备份。 </li></ol>气缸测试3.实验装置<ol><li>紧固在下表镜以45度角的桌面。别连接于桌腿此使用两个支架，以suppor吨反射镜的顶部和底部，分别。托架位置将记录在一个侧视图表（ 图1A）和表（ 图1B）的一个面上视图。 </li><li>放置气缸在桌子的中央。绘制四个等距线所在的气缸坐在桌子上用黑色标记（SHARPIE），使得筒可以解除并返回到相同的位置（ 图2）。绘制它们在透明桌面的下侧允许桌面到动物试验之间进行清洗而不溶解的标记油墨。 </li><li>连接相机和三脚架。将相机对准镜子使画面直接翻翻缸筒。确保气缸的充分内壁是可见的和通畅由基座（ 图3）。见设置的侧上视图，包括相机和镜设置的相对角度，从上方（ 图4A），并从表中的电平，包括一个鼠标饲养（ 图4B）。 </li><li>准备提示卡识别之前拍摄每个鼠标。确保卡通常包括用于每个小鼠的识别号码，时间点的测试（ 例如 ，治疗后3天），并拍摄会议日期。不包括在提示卡上的治疗组，以确保实验者被蒙蔽。 </li><li>电影标准的室内照明条件的光这个水平需要清楚地看到围绕气瓶的鼠标移动。 注:如果拍戏可以在一个红灯照相机可能就足够了黑暗，但是人们会首先需要测试的爪子触摸并拖动是否清晰定量可见。 </li></ol> 4.执行<ol><li>开始拍摄。显示适当的鼠标提示卡在镜头前。 </li><li>拍摄提示卡后，立即放下鼠标到从开顶缸。 </li><li>开始拍摄鼠标。在此期间尽量减少噪音，老鼠可能丢失，如果一震探索的兴趣。 </li><li>观察小鼠后探索缸。捕捉视频，直到鼠标执行最低二十后轮。 注意:当两个前爪失去与地面接触和鼠标站在其后腿，则发生后方。 </li><li>擦拭桌面和汽缸，每个鼠标之间取得适当的清洗液消毒和消除气味鼠标。 </li><li>冰点是当小鼠停止探索，并保持安静地坐在四肢着大约5分钟。如果小鼠冻结20后轮发生之前，就可能有必要恢复试验前从气缸移除它们10-20分钟。如果小鼠不执行20后轮，它们从研究中删除。 注:根据我们的经验，老鼠从未需要被排除由于未能探索缸。 </li></ol>气缸测试5.使用评估爪拖分析<ol><li>播放视频时的0.25倍之间和0.67X正常速度的速度取决于如何快速的鼠标探索气缸。使用媒体播放器，提供了更慢的播放速度。 </li><li>量化爪子触摸的总数。爪子触摸发生时，鼠标后轮（ 图5A），触摸气缸（ 图5B）的一侧，随后与两个爪同时（ 图5C）和平台（ 图5D）卸除。爪可以或可以不具有充分手掌接触汽缸壁，但与汽缸壁部分接触必须发生。通过与气缸壁的一个或两个前爪（无论多么短暂）计数的次数鼠标进行接触而站在其后肢的后期间评估爪子触摸。 注意与汽缸壁的接触只算作一个"爪子触摸"或"爪拖"如果鼠标在后方位置 - 站立它的后肢与两个前爪离台面。如果鼠标停留在3点的姿态 - 既后肢和一个前爪在桌面上，并进入与自由爪子触壁 - 这不算是一个爪子触摸。小鼠可后部并碰触所述汽缸壁具有单个前爪和这个被算作一个爪子触摸。注:鼠标也可后移动时它身体的圆筒周围，使两个以上的联系人。这些触点相符 - 每个左前爪touch和为每个右前爪联系。 </li><li>量化爪拖动的数量。 PAW-拖动行为是正常的爪子接触不同。 <ol><li>如果爪子接触到气缸壁采用了全开放式的手掌（ 图6B），它会慢慢地从墙上掉下去，经常有轻微的震颤。运动与拖靠在汽缸壁或者在内侧或向下的方向，（ 图6C）的数字开始落下远COMPLET前伊利（ 图6D）。鼠标会再登陆四肢着地（ 图6F）之前，其未受影响的爪子（ 图6E）下马。这被认为是一个爪子拖动，并应在理货计数。 </li><li>如果爪不与一个完全开放的手掌接触汽缸壁，它将从气缸壁落下离开之前轻擦气缸壁与它的位数。同样，鼠标可能拖累它的爪子在气缸壁上，但拆卸之前不释放完全。这些都被认为PAW-拖动以及触摸和理货应该算作两个。 </li><li>爪也可沿着汽缸壁拖动而鼠标探讨了圆柱体。在这种情况下，爪将跟随鼠标的躯干的扭转，因为它拆卸（ 图7E）之前探讨左侧的原来的位置（ 图7A-D）或右。这不被认为是一个爪拖动的，因为它依赖于小鼠随机选择一个方向探索和不依赖于它的皮质半球受损。 </li></ol></li><li>每个爪子触摸总数在会话期间PAW-拖动表示为百分比爪一拖再拖。表达爪拖动为每个单独前肢爪总接触的百分比数。 </li><li>导致一爪子拖动触摸算作一个爪子拖动，同时触摸。因此，如果一个鼠标每次拖动它的爪子其爪子所述汽缸壁接触，爪拖动百分比表示为100％。 </li></ol> 6.附加的实验设计建议<ol><li>为了尽量减少多余的变量: <ol><li>测试小鼠在同一时间上的每个测试日。在其唤醒周期测试小鼠。小鼠保持在12小时反光照周期有利于性能。 </li><li>小鼠可能不愿意探索如果因噪音或小说环境强调圆柱体。在他们的动物收容室或一室老鼠的测试他们bEEN熟悉减轻压力。这可能发生，如果房间吵，如果鼠标已经推挤进入气缸之前，或由于习惯。 注意:测试应一次实验操作前进行以用作基线读数。操纵后，测试天都在实验者的判断，尽管它是应避免过度的短时间内过多暴露到气缸。 </li><li>老鼠可能会变得不愿意后6-7后暴露于气缸。对于目前的研究中，将小鼠在汽缸中总共七次，缺血前和天1，3，7，14，21和28后的手术进行测试。 注:在本研究中，我们使用了FVBN小鼠品系。我们先前测试之C57B1 / 6小鼠的气缸和观察到的爪拖动行为以下内容的ET-1的缺血性损伤的（数据未显示）。饲养时C57BL / 6小鼠比FVBN小鼠更积极和频繁跳上筒的轮缘之前爬出来。如果老鼠试图通过跳跃逃跑更高的钢瓶应该被使用。 </li></ol></li></ol> 7.内皮素-1手术及脑梗塞体积的测量<ol><li>根据此前公布的协议执行4内皮素-1手术和梗死体积的测量。为目标的前部前肢运动皮层，将每只小鼠应该接受3 ET-1注射在以下坐标:（ⅰ）0.7 anteriorposterior（AP）/1.5内侧 - 外侧（毫升）/ - 1.2背腹（DV），（ ⅱ）+0.4 AP /1.25毫升/ - 1.2 DV和（ⅲ）0.1 AP /1.75毫升/ -1.2 DV 4。 </li></ol> 8.统计分析<ol><li>建议方差双向重复测量分析（ANOVA）来分析爪拖动跨不同的时间点的影响和未受影响的爪子的百分比。 </li></ol>

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量化爪拖动行为时，在气缸测试有以下要点建立:我）量化数PAW-拖动与总爪子触摸脑损伤之前，每个爪子建立一个基线;二）量化爪拖动与总爪子触摸每个爪子下面的缺血性损伤的数量;和iii）一个爪拖动并沿气缸壁的爪子的期间小鼠的躯干的横向转动的横向运动区分。 PAW-拖动是出现损伤后的前肢感觉运动皮层的新型行为。的爪式拖行为的外观因此可以用作该前肢感觉皮层已?...

神经再生战略的目标是展示两个组织修复和功能的恢复。功能恢复通常评估与测量功能缺陷，在这种情况下，涉及了与损害特定脑区域相关联的运动技能行为测试。创伤性脑损伤或脑皮层的感觉运动前肢区局部缺血损伤可以由许多行为测试来证明。一个这样的试验中，在气缸试验被广泛使用的大鼠，以评估在前肢活动1的功能缺陷。测试具有低的建立费用，仅需要一个气缸，照相机和表用透明顶部。这是很容易，因为它是基于啮齿动物的自然探索行为来管理，所以训练前和食物剥夺或奖励不是必需的。尽管有这些众多的优势，在气缸测试下，利用下面的焦点受伤的前肢s到评估小鼠前肢赤字ensorimotor皮层，这是我们归因于对鼠标行为的气瓶检验分析。前肢不对称是经典测度分析气缸测试。当放置在气缸中，啮齿动物，自然由饲养到其后肢和接触汽缸壁与他们的前肢的爪子对姿势平衡探索汽缸的壁。爪接触与壁与每个前肢的数目很容易被这种探索气缸期间拍摄啮齿类定量。当受影响的前肢的爪子，使更少的接触与墙体比未受影响前肢的爪子，表明损坏对侧感觉皮层发生前肢不对称。在大鼠中，血管收缩剂的内部皮质注射剂，内皮素（ET-1），进前肢感觉皮层引起局灶性缺血损伤，这导致行为缺陷在对侧前肢。在对侧前肢使用赤字很容易检测到的变化f中在大鼠1-3缸测试orelimb不对称。在对比然而大鼠，改变前肢不对称是可变的，在小鼠中以下可比的ET-1注射4-6不太一致。在这里，我们展示了一个新的汽缸测试前肢行为分析 - 中爪拖行为分析。我们以前曾表明，爪拖动分析是损坏的小鼠比经典前肢不对称分析前肢感觉皮层的更灵敏的测量，因此是适用于各种局灶性皮质损伤模型。 检查如何前爪接触汽缸壁以下的前肢感觉皮层缺血损伤揭示了一种新的行为在小鼠-爪拖动4。当鼠标站在其后腿探索气缸壁，然后沿筒​​壁对其中线或向下的墙面上，同时拖动其受影响（禁忌病变）发生足一爪子拖它的前爪不受影响提供靠墙的姿势支持。 PAW-拖动很少发生在未受伤的老鼠因此爪子拖动的外观是受伤的前肢感觉运动皮层4正面指标。我们先前量化以下的前肢感觉皮层ET-1的局部缺血损伤的小鼠爪拖动行为和表现出持续爪拖动行为小鼠长达两周中风后4。在这里，我们表明，爪拖动行为是持续长达四周后中风。爪的拖行为分析提供了一种新的和敏感的工具，以评估在小鼠前肢感觉运动皮层局灶性缺血性脑损伤。以其物美价廉的设置，便于管理和得分使这个简单，但非常有用的工具，以快速评估在小鼠前肢行为缺陷。

<table><tbody><tr><td>Plexi-glass cylinder</td><td></td><td></td><td>17.5 cm high, 9.5 cm outer diameter, 8.8 cm inner diameter, wall thickness 0.35 cm (or 3.5 mm)</td></tr><tr><td>viewing table</td><td></td><td></td><td>54x56x66.5 cm (width x length x height), top of table is a 51x51 cm sheet of plexiglass.</td></tr><tr><td>mirror</td><td></td><td></td><td>34x58 cm mirror</td></tr><tr><td>video camera</td><td>Sony</td><td>DCR-SR42</td><td>Video camera with onboard storage, SD functionality, 40x optical zoom</td></tr><tr><td>computer</td><td>Dell</td><td>Optiplex 760</td><td>Processor: Intel, 3.0 GHz, Memory 4.00GB (RAM)&amp;nbsp;</td></tr><tr><td>computer monitor</td><td>Samsung</td><td>S22C350H</td><td></td></tr><tr><td>Excel (Microsoft Office Professional Plus)</td><td>Microsoft</td><td>v14.0.7106.5003</td><td></td></tr><tr><td>VLC Media Player</td><td>Video LAN</td><td>v2.1.2</td><td>Media player with playback speed modulation and video support</td></tr><tr><td>External Hard Drive</td><td>Western Digital</td><td>WDBAAU0020HBK-01</td><td>2 TB</td></tr></tbody></table>

paw-dragging: a novel, sensitive analysis of the mouse cylinder test

气缸试验常规地用于预测给前肢运动皮层在啮齿类动物局灶性缺血损伤。当放置在气缸中，啮齿动物探索由饲养和触摸气缸的壁与他们的前肢的爪子对姿势支承。缺血性损伤的前肢感觉运动皮层，老鼠更多地依赖于他们的前肢不受影响的爪子导致其受影响的爪子被称为前肢不对称较少触及姿势的支持。与此相反，在小鼠脑局灶性缺血损伤未能导致前肢不对称可比一致赤字。虽然前肢不对称赤字很少观察到，老鼠也表现出了一种新的行为中风后称为"爪拖"。 PAW-拖动是鼠标沿筒壁，而不是直接从墙壁从后方拆卸到一个四条腿的立场时，推下拖动其受影响的爪子的倾向。之前我们已经表明，PAW-拖动行为是小皮质缺血性损伤的前肢运动皮层高度敏感。在这里，我们为爪拖分析了详细的方案。我们定义什么是爪子拖就是和演示如何量化爪拖行为。气缸试验是一种简单且廉价的检验管理，并且不需要预训练或食物剥夺策略。在使用爪拖动分析与汽缸测试，它填补利基预测皮质缺血性损伤如photothrombosis和内皮素-1（ET-1）诱导的缺血 - 两个模型被不断增加的流行度，并产生更小的焦距受伤比大脑中动脉闭塞。最后，测量气缸测试爪拖动行为将使功能恢复使用的转基因小鼠品系，其中前面的前肢不对称分析未能检测到一致的赤字广泛队列皮质损伤后的研究。

之前我们已经证实看来，爪子拖行为遵循局灶性缺血损伤的前肢感觉运动皮层和损坏4的正面指标。 ET-1的内皮层注射入前肢感觉皮层被用来诱导局部缺血损伤（ 图8A，B）。本研究的爪子拖动行为是否延期超过14天受伤后其潜在用途，以评估功能恢复。小鼠在当日气缸试验前的ET-1注射的手术前的时间点，并在天1，3，7，14，21和28后的损伤进行测试。在每个时间点，爪子触摸和?...

Watch this Scientific Journal Video about Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test at JoVE.com

Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test

气缸测试的经典前肢不对称分析常规地用于评估脑损伤或中风大鼠行为缺陷;但是，它无法检测一致赤字小鼠。这项研究表明，量化爪拖动行为是脑损伤的小鼠更敏感的分析。

PAW-拖动:一本小说，鼠标缸试验敏感性分析

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore ...

paw-dragging-a-novel-sensitive-analysis-of-the-mouse-cylinder-test

Universidad de Cartagena UDEC

Research

JoVE Journal

Behavior

23.3K 次观看.  Memorial University of Newfoundland. 气缸测试的经典前肢不对称分析常规地用于评估脑损伤或中风大鼠行为缺陷;但是，它无法检测一致赤字小鼠。这项研究表明，量化爪拖动行为是脑损伤的小鼠更敏感的分析。 

视频: Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test

Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease

Sensitive and reliable behavioral outcome measures are essential to the evaluation of potential therapeutic treatments in preclinical trials for many neurodegenerative diseases. In Parkinson's disease, sensorimotor tests sensitive to varying degrees of nigrostriatal dysfunction are fundamental for testing the efficacy of potential therapeutics. Reliable and quite elegant sensorimotor measures exist for rats, however many of these tests measure sensorimotor asymmetry within the rat and are not entirely suitable for the newer genetic mouse models of PD. We have put together a battery of sensorimotor tests inspired by the sensitive tests in rats and adapted for mice. The test battery highlighted in this study is chosen for a) its sensitivity in a wide variety of mouse models of PD, b) its ease in implementing into a study, and c) its low expense. These tests have proven useful in characterizing novel genetic mouse models of PD as well as in testing potential disease-modifying therapies.

In Parkinson's disease and movement disorders in general, sensitive and reliable behavioral assays are essential for testing novel potential therapeutics. Here, we describe a manageable battery of sensorimotor tests for mice that are sensitive to varying degrees of injury to the nigrostriatal system and useful for preclinical studies.

帕金森氏症小鼠模型的感觉功能评估

Sensitive and  reliable behavioral outcome measures are essential to the evaluation of  potential therapeutic treatments in preclinical trials for many  ...

科研

行为学

The Vermicelli and Capellini Handling Tests: Simple quantitative measures of dexterous forepaw function in rats and mice

Previous characterizations of rodent eating behavior have revealed that they use coordinated forepaw movements to manipulate food pieces. We have extended upon this work to develop a simple quantitative measure of forepaw dexterity that is sensitive to lateralized impairments and age-dependent changes. Rodents learn skillful forepaw and digit movements to manage thin pasta pieces, which they eagerly consume. We have previously described methods for quantifying vermicelli handling in rats and showed that the measures are very sensitive to forelimb impairments resulting from unilateral ischemic lesions, middle cerebral artery occlusions and unilateral striatal dopamine depletion [Allred, R.P., Adkins, D.L., Woodlee, M.T., Husbands, L.C., Maldonado M.A., Kane, J.R., Schallert, T. &amp; Jones, T.A. The Vermicelli Handling Test: a simple quantitative measure of dexterous forepaw function in rats. J. Neurosci. Methods 170, 229-244 (2008)]. Here we present a more detailed protocol for this test in rats and compare it with a newly developed version for mice, the Capellini Handling Test. Rats and mice are videotaped while handling short lengths of uncooked vermicelli or capellini pasta, respectively, with a camera positioned to optimize the view of paw movements. Slow motion video playback allows for the identification of forepaw adjustments, defined as any distinct removal and replacement of the paw, or of any number of digits, on the pasta piece after eating commences. Forepaw adjustments per piece are averaged over trials per each testing session. Repeated testing permits sensitive quantitative analysis of changes in forepaw dexterity over time. Protocols for pre-testing habituation and handling practice, as well as procedures for characterizing atypical handling patterns, are described. Because rats and mice perform the pasta handling tests slightly differently, species-specific differences in administration and scoring of these tests are highlighted. All animal use was in accordance with protocols approved by the University of Texas at Austin Animal Care and Use Committee.

The Vermicelli and Capellini Handling Tests of forepaw dexterity take advantage of the natural inclination of rodents to manipulate food items using skillful forepaw and digit movements. Animals are videotaped while handling short strands of uncooked dry pasta. Slow motion video playback allows for the quantification of forepaw adjustments.

粉条和Capellini处理测试：在大鼠和小鼠的灵巧的前爪功能简单的定量措施

Previous characterizations of rodent eating behavior have revealed that they use coordinated forepaw movements to manipulate food pieces. We have extended ...

神经科学

Assessing Functional Performance in the Mdx Mouse Model

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder for which no cure is available. Nevertheless, several potential pharmaceutical compounds and gene therapy approaches have progressed into clinical trials. With improvement in muscle function being the most important end point in these trials, a lot of emphasis has been placed on setting up reliable, reproducible, and easy to perform functional tests to pre clinically assess muscle function, strength, condition, and coordination in the mdx mouse model for DMD. Both invasive and noninvasive tests are available. Tests that do not exacerbate the disease can be used to determine the natural history of the disease and the effects of therapeutic interventions (e.g. forelimb grip strength test, two different hanging tests using either a wire or a grid and rotarod running). Alternatively, forced treadmill running can be used to enhance disease progression and/or assess protective effects of therapeutic interventions on disease pathology. We here describe how to perform these most commonly used functional tests in a reliable and reproducible manner. Using these protocols based on standard operating procedures enables comparison of data between different laboratories.

Assessing Functional Performance in the Mdx Mouse Model

The primary outcome measure in clinical trials for neuromuscular disorders is generally improved muscle function. Therefore, assessing the effect of potential therapeutic compounds on muscle performance pre clinically in mouse models is of great importance. We here describe several functional tests to address this.

评估在功能性能<em&gt; MDX</em&gt;小鼠模型

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder for which no cure is available. Nevertheless, several potential ...

Measuring Motor Coordination in Mice

Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such as emotionality or cognition can be assessed, however, it is vital to determine whether the motor capabilities of e.g. a mutant or lesioned mouse allow such an assessment. Performance on a maze task requiring strength and coordination, such as the Morris water maze, might well be impaired in a mouse by motor, rather than cognitive, impairments, so it is essential to selectively dissect the latter from the former. For example, sensorimotor impairments caused by NMDA antagonists have been shown to impair water maze performance2. 
Motor coordination has traditionally been assessed in mice and rats by the rotarod test, in which the animal is placed on a horizontal rod that rotates about its long axis; the animal must walk forwards to remain upright and not fall off. Both set speed and accelerating versions of the rotarod are available.
The other three tests described in this article (horizontal bar, static rods and parallel bars) all measure coordination on static apparatus. The horizontal bar also requires strength for adequate performance, particularly of the forelimbs as the mouse initially grips the bar just with the front paws. 
Adult rats do not perform well on tests such as the static rods and parallel bars (personal observations); they appear less well coordinated than mice. I have only tested male rats, however, and male mice seem generally less well coordinated than females. Mice appear to have a higher strength:weight ratio than rats; the Latin name, Mus musculus, seems entirely appropriate. The rotarod, the variations of the foot fault test12 or the Catwalk (Noldus)15 apparatus are generally used to assess motor coordination in rats.

Protocols are presented for two established motor coordination tasks, the accelerating rotarod and horizontal bar, also two tests developed in Oxford recently, the static rods and parallel bars. These tests can detect motor impairments potentially of interest in their own right, as well as being possible variables in tests of other areas of behavior.

测量小鼠运动协调

Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such ...

Low-cost Protocol of Footprint Analysis and Hanging Box Test for Mice Applied the Chronic Restraint Stress

Gait disturbance is frequently observed in patients with movement disorders. In mouse models used for movement disorders, gait analysis is important behavioral test to determine whether the mice mimic the symptoms of patients. Motor deficits are often induced by stress when no spontaneous motor phenotype is observed in the mouse models. Therefore, gait analysis followed by stress loading would be a sensitive method for evaluating the motor phenotype in mouse models. However, researchers face the requirement of an expensive apparatus to obtain quantitative results automatically from gait analysis. For stress, stress loading by simple methods without expensive apparatuses required for electric shock and forced running is desirable. Therefore, we introduce a simple and low-cost protocol consisting of footprint analysis with paper and ink, hanging box test to evaluate motor function, and stress loading defined by restraint with a conical tube. The motor deficits of mice were successfully detected by this protocol.

The low-cost protocol consisting of footprint analysis and hanging box test after restraint stress is useful for evaluating the movement disorders of mouse model.

小鼠应用慢性约束应激的低成本足迹分析和吊箱试验协议

Gait disturbance is frequently observed in patients with movement disorders. In mouse models used for movement disorders, gait analysis is important ...

Measuring Changes in Tactile Sensitivity in the Hind Paw of Mice Using an Electronic von Frey Apparatus

Measuring inflammation-induced changes in thresholds of hind paw withdrawal from mechanical pressure is a useful technique to assess changes in pain perception in rodents. Withdrawal thresholds can be measured first at baseline and then following drug, venom, injury, allergen,&#160;or otherwise evoked inflammation by applying an accurate force on very specific areas of the skin. An electronic von Frey apparatus allows precise assessment of mouse hind paw withdrawal thresholds that are not limited by the available filament sizes in contrast to classical von Frey measurements. The ease and rapidity of measurements allow for incorporation of assessment of tactile sensitivity outcomes in diverse models of rapid-onset inflammatory and neuropathic pain as multiple measurements can be taken within a short time period. Experimental measurements for individual rodent subjects can be internally controlled against individual baseline responses and exclusion criteria easily established to standardize baseline responses within and across experimental groups. Thus, measurements using an electronic von Frey apparatus represent a useful modification of the well-established classical von Frey filament-based assays for rodent mechanical allodynia that may also be applied to other nonhuman mammalian models.

Electronic von Frey measurements are an effective and improved alternative to classical von Frey filaments, as they allow rapid and precise measurement of changes in rodent mechanical withdrawal thresholds to continuously applied pressure stimuli before and after an inflammatory event.

Measuring inflammation-induced changes in thresholds of hind paw withdrawal from mechanical pressure is a useful technique to assess changes in pain ...

Assessment of Mouse Judgment Bias through an Olfactory Digging Task

Judgment biases (JB) are differences in the way that individuals in positive and negative affective/emotional states interpret ambiguous information. This phenomenon has long been observed in humans, with individuals in positive states responding to ambiguity 'optimistically' and those in negative states instead showing 'pessimism'. Researchers aiming to assess animal affect have taken advantage of these differential responses, developing tasks to assess judgment bias as an indicator of affective state. These tasks are becoming increasingly popular across diverse species and fields of research. However, for laboratory mice, the most widely used vertebrates in research and a species heavily relied upon to model affective disorders, only one JB task has been successfully validated as sensitive to changes in affective state. Here, we provide a detailed description of this novel murine JB task, and evidence of its sensitivity to mouse affect. Though refinements are still necessary, assessment of mouse JB opens the door for answering both practical questions regarding mouse welfare, and fundamental questions about the impact of affective state in translational research.

This article provides a detailed description of a novel mouse judgment bias protocol. Evidence of this olfactory digging task's sensitivity to affective state is also demonstrated and its utility across diverse research fields is discussed.

通过嗅觉挖掘任务评估小鼠判断偏差

Judgment biases (JB) are differences in the way that individuals in positive and negative affective/emotional states interpret ambiguous information. This ...

A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy

As the sheer number of transgenic mice strains grow and rodent models of pediatric disease increase, there is an expanding need for a comprehensive, standardized battery of neonatal mouse motor tests. These tests can validate injury or disease models, determine treatment efficacy and/or assess motor behaviors in new transgenic strains. This paper presents a series of neonatal motor tests to evaluate general motor function, including ambulation, hindlimb foot angle, surface righting, negative geotaxis, front- and hindlimb suspension, grasping reflex, four limb grip strength and cliff aversion. Mice between the ages of post-natal day 2 to 14 can be used. In addition, these tests can be used for a wide range of neurological and neuromuscular pathologies, including cerebral palsy, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, neurodegenerative diseases, and neuromuscular disorders. These tests can also be used to determine the effects of pharmacological agents, as well as other types of therapeutic interventions. In this paper, motor deficits were evaluated in a novel neonatal mouse model of cerebral palsy that combines hypoxia, ischemia and inflammation. Forty-eight hours after injury, five tests out of the nine showed significant motor deficits: ambulation, hindlimb angle, hindlimb suspension, four limb grip strength, and grasping reflex. These tests revealed weakness in the hindlimbs, as well as fine motor skills such as grasping, which are similar to the motor deficits seen in human cerebral palsy patients.

Presented is a concise battery of mouse neonatal motor tests. Using these tests, neonatal motor deficits can be demonstrated in a variety of neonatal motor disorders. By having a standardized set of tests, results from different studies can be compared, allowing for better and accurate reporting between groups.

汽车测试的脑瘫新生儿小鼠模型电池

As the sheer number of transgenic mice strains grow and rodent models of pediatric disease increase, there is an expanding need for a comprehensive, ...

医学

The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse

A major symptom of patients with osteoarthritis (OA) is pain that&#160;is triggered by peripheral as well as central changes within the pain pathways. The current treatments for OA pain such as NSAIDS or opiates are neither sufficiently effective nor devoid of detrimental side effects. Animal models of OA are being developed to improve our understanding of OA-related pain mechanisms and define novel pharmacological targets for therapy. Currently available models of OA in rodents include surgical and chemical interventions into one knee joint. The monoiodoacetate (MIA) model has become a standard for modelling joint disruption in OA in both rats and mice. The model, which is easier to perform in the rat, involves injection of MIA into a knee joint that induces rapid pain-like responses in the ipsilateral limb, the level of which can be controlled by injection of different doses. Intra-articular injection of MIA disrupts chondrocyte glycolysis by inhibiting glyceraldehyde-3-phosphatase dehydrogenase and results in chondrocyte death, neovascularization, subchondral bone necrosis and collapse, as well as inflammation. The morphological changes of the articular cartilage and bone disruption are reflective of some aspects of patient pathology. Along with joint damage, MIA injection induces referred mechanical sensitivity in the ipsilateral hind paw and weight bearing deficits that are measurable and quantifiable. These behavioral changes resemble some of the symptoms reported by the patient population, thereby validating the MIA injection in the knee as a useful and relevant pre-clinical model of OA pain.
The aim of this article is to describe the methodology of intra-articular injections of MIA and the behavioral recordings of the associated development of hypersensitivity with a mind to highlight the necessary steps to give consistent and reliable recordings.

Osteoarthritis (OA), or degenerative joint disease, is a debilitating condition associated with pain that remains only partially controlled by available analgesics. Animal models are being developed to improve our understanding of OA-related pain mechanisms. Here we describe the methodology for the monoiodoacetate model of OA pain in the mouse.

骨关节炎疼痛的鼠标Monoiodoacetate模式

A major symptom of patients with osteoarthritis (OA) is pain that&#160;is triggered by peripheral as well as central changes within the pain pathways. The ...

Mechanical Conflict-Avoidance Assay to Measure Pain Behavior in Mice

Pain comprises of both sensory (nociceptive) and affective (unpleasant) dimensions. In preclinical models, pain has traditionally been assessed using reflexive tests that allow inferences regarding pain's nociceptive component but provide little information about the affective or motivational component of pain. Developing tests that capture these components of pain are therefore translationally important. Hence, researchers need to use non-reflexive behavioral assays to study pain perception at that level. Mechanical conflict-avoidance (MCA) is an established voluntary non-reflexive behavior assay, for studying motivational responses to a noxious mechanical stimulus in a 3 chamber paradigm. A change in a mouse's location preference, when faced with competing noxious stimuli, is used to infer the perceived unpleasantness of bright light versus tactile stimulation of the paws. This protocol outlines a modified version of the MCA assay which pain researchers can use to understand affective-motivational responses in a variety of mouse pain models. Though not specifically described here, our example MCA data use the intraplantar complete Freund's adjuvant (CFA), spared nerve injury (SNI), and a fracture/casting model as pain models to illustrate the MCA procedure.

The mechanical conflict-avoidance assay is used as a non-reflexive readout of pain sensitivity in mice which can be used to better understand affective-motivational responses in a variety of mouse pain models.

机械冲突避免测定测量小鼠疼痛行为

Pain comprises of both sensory (nociceptive) and affective (unpleasant) dimensions. In preclinical models, pain has traditionally been assessed using ...