Name: a novel approach to assess motor outcome of deep brain stimulation effects in the hemiparkinsonian rat: staircase and cylinder test
Uploaded: 2016-05-31T13:00:00.000+00:00
Duration: 7 min 14 s
Description: Watch this Scientific Journal Video about A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test at JoVE.com

This work was supported by Interdisziplin&#228;res Zentrum f&#252;r Klinische Forschung (IZKF), University Clinics W&#252;rzburg, Germany (project N-215).

动物实验是由维尔茨堡大学和下弗兰肯行政区的法律国家机关按照动物保护准则和欧洲共同体委员会的指导方针（:55.2-2531.01十一分之七十六批准文号）批准。所有作出了努力，尽量减少使用动物的疼痛或不适。 注:18别处描述进行植入电极。 1.气缸试验（图2） <ol><li>通过用0.1％的醋酸溶液清洗筒准备一个透明的塑料玻璃圆筒（19厘米的高度:40厘米，直径）。 </li><li>与试验的日期和各组大鼠的识别号码准备卡。 </li><li>将两个镜子的背后汽缸90°角。 </li><li>将相机放置在圆筒的前部，使得照相机和气缸之间的距离允许爪子的良好视图。 </li><li>放置在运输箱的老鼠。 注意:动物应通过在测试之前，以避免应力实验者处理。 </li><li>从运家笼老鼠使用运输箱筒。 </li><li>放置老鼠的气缸（ 图3）英寸<ol><li>总是在一天的同一时间执行所有行为试验，以避免在活动的昼夜的差别。如果动物连接到由电缆的刺激发生器确保电缆在实验过程中不扭曲。 </li></ol></li><li>按下相机的"记录"按钮。显示用实验和大鼠的识别号码到摄像机的实际日期的卡。开始录制。 </li><li>五分钟后，取出从气缸动物，并把它放回使用运输箱的家笼。 </li><li>清洁用0.1％乙酸溶液中的圆柱体。 </li><li>通过计算左和右爪壁接触（百分比爪子使用），以及为r评估从记录的视频爪使用耳环（上后爪站在有或没有支撑在汽缸壁）。气缸试验也可通过适当的软件自动进行评价。 注:一个健康的老鼠同时使用爪子一样。帕金森病的老鼠使用的影响，由于病变程度较轻爪子。 </li></ol> 2.楼梯测试（图4） <ol><li>采集阶段<ol><li>训练的前一天熟悉的动物在楼梯测试中使用的颗粒。 <ol><li>可选:要增加动物的动机使用限制饮食（10-15 g标准的实验室食物的在自由摄食16级的90％，以保持体重）。然而，这不是强制性的，以实现正的训练效果。这项研究是没有食物限制进行。 </li></ol></li><li>制备透明塑料玻璃楼梯盒（高度34.5厘米，长35.5厘米，宽:12厘米和窄室6厘米）由清洁框用0.1％的交流客位酸溶液。注意:楼梯盒是一个两室盒与一个凸起的平台，并在狭窄隔室2楼梯。在狭窄的隔间楼梯左侧步骤只能与左爪到达，仅与右爪的正确步骤。 注意:标准梯箱包括两个隔室的盖子，如果它是用于实验经由电缆刺激大鼠，使用高盒子无盖。 </li><li>拆下楼梯，填补八个45毫克颗粒每一步井。 </li><li>将楼梯，并把另外八个小球高涨的平台上。 </li><li>放置在运输箱的老鼠。 </li><li>从运家笼老鼠使用运输箱楼梯框。 </li><li>放置在楼梯框大鼠（ 图5）。 </li><li>五分钟后，取出从楼梯盒子动物，并把它放回使用运输箱的家笼。 </li><li>注多少颗粒从平台和（最终）从右边和左边的楼梯食用。 </li><li>通过填写上有八个45毫克颗粒每一步井笔芯的楼梯。 </li><li>清洁用0.1％乙酸溶液中的楼梯框并将附加粒料在平台上。 </li><li>重复此过程（获取阶段），连续三天。 注意:所述的对雄性Sprague Dawley大鼠进行所有的实验。不同的培训模块的持续时间可以在不同的应变，性别和厂商的老鼠不同。 </li></ol></li><li>自由选择测试<ol><li>清洁用0.1％乙酸溶液中的楼梯框。 </li><li>拆下楼梯，填补八个45毫克颗粒每一步井。 </li><li>放置在运输箱的老鼠。 </li><li>从运家笼老鼠使用运输箱楼梯框。 </li><li>放置在楼梯框中的老鼠。 </li><li>五分钟后，从楼梯取出动物案例盒，把它放回使用运输箱的家笼。 注意:有多少小球从右侧和左侧的楼梯食用。 </li><li>注意:如果动物仍然有抓小球的问题，增加更多的一些平台，让他们可以很容易达成。 </li><li>通过填写上有八个45毫克颗粒每一步井笔芯的楼梯。 </li><li>与下一个动物0.1％的醋酸溶液清洗楼梯框。 </li><li>重复此过程（自由选择阶段）连续三天。 注:提供的结果是由无模块之间的休息时间进行训练获得。有些团体喜欢休息日进行整合，以支持训练过程。 </li></ol></li><li>强迫选择测试<ol><li>清洁用0.1％乙酸溶液中的楼梯框。 </li><li>除去楼梯和具有八个（模块前三天）或四个（连续THR填补左侧楼梯每个步骤的孔模块）45毫克颗粒EE天。 <ol><li>就在旁边，在那里将发生减值进行强制选择题。 注意:我们在右半球进行帕金森病变，因此选择培训左爪子。 </li></ol></li><li>放置在运输箱的老鼠。 </li><li>从运家笼老鼠使用运输箱楼梯框。 </li><li>放置在楼梯框中的老鼠。 </li><li>五分钟后，取出从楼梯盒子动物，并把它放回使用运输箱的家笼。 </li><li>注意有多少沉淀左楼梯吃掉。 </li><li>通过填写上有八个或四个45毫克的颗粒（颗粒的数量取决于训练日）的每一步井笔芯的楼梯。 </li><li>与下一个动物0.1％的醋酸溶液清洗楼梯框。 </li><li>重复此过程（迫选阶段）连续六天。 </li></ol></li><li>数据采集<ol> &lt;利&gt;作为用于强迫选择模块（在，每四个小球以及左侧楼梯）连续两天的说明来执行该实验。计算的成功率（吃掉粒料数目），为两天的平均值。 </li></ol></li></ol>

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The authors declare that they have no competing financial interests.

本文介绍了气缸和楼梯测试详细的培训方案。后者的目的是评估复杂抓行为和精细运动运动由于大鼠16,17熟练深远。结果测量被表示为试验，这是一种客观测量期间吃掉粒料数目。该协议可以在大鼠模型被用于帕金森病和其它运动疾病模型。气缸测试涉及一个简单的方法来评估大鼠爪子的使用。它无需培训，并且可以在一个高度标准化的方式从录像带被使用，由盲评价。我们选择有几个原...

底丘脑核（STN）的脑深部刺激为帕金森氏病1和其他运动障碍的有效治疗选择。基本的机制仍然知之甚少和多因素的，但是一个重要特点是神经元网络活动通过在刺激电极2-4的附近轴突重复去极化调制。高频（&gt; 100赫兹）刺激，需要在大多数脑目标和DBS的最适应症的有益效果。从其他纤维，其通过刺激体积覆盖并且其中无意共激活深部脑刺激导致的副作用对...有用不同的功能，例如锥体束。因此，人们希望开发刺激参数，其中优先激活有益神经元素，同时避免副作用元件5,6的共激活。虽然神经生理学可以提供这种精细呕吐DBS的NG选项，科学发展在过去二十年中已经微乎其微，因为编程策略主要是被用在患者的"试错"评估和限用市售DBS设备有限编程选项，而不是使用神经生理学的洞察力并确定实验设置，系统地探索完整的参数空间。 为了克服DBS研究平移路障，我们提出了一个协议，在筛查临床探索之前帕金森的啮齿动物模型替代刺激参数。单方面帕金森氏大鼠疾病用6-羟多巴胺注射仿照到右内侧前脑束7,8。由此产生的病变，进一步描述为帕金森病，低剂量注射阿朴吗啡旋转后成绩评价阿朴吗啡试验进行评估和确认验尸由酪氨酸羟化酶immunohistochemistry。该方法是容易应用和高重现性的，而轴承的低死亡率和发病率。由此产生的运动障碍是非常离散7,8;这些动物都在自发的探索和把握复杂的行为表现出9,10对侧左爪子轻微受损。 评估的脑深部刺激协议测试需要其允许测量电机性能的快速和可靠的变化和可重复随着时间的推移与不同神经刺激的设置的有效性。一些研究小组已经提出了不同的激励方法和不同的测试，以评估在大鼠11高度可变和不一致的结果11-14的运动功能。这迫使我们选择了一套具有高测试预测效度和互补性。此外，对于脑深部刺激条件下，电机结果的评估，测试被看好这可以通过ANI进行MALS通过电缆连接到所述刺激发生器。为了这些目的，我们建立了我们的测试电池由一个测试用爪子不对称和对技术达到一个测试的。研究设计在图1中示出。 自发爪子使用我们执行通过Shallert 15，其是垂直勘探期间爪子使用广泛使用的测试中描述的气缸试验。动物没有训练是必需的。对于更复杂的抓行为的评估，我们根据蒙托亚16建立的楼梯测试。我们的协议是根据Kloth 17修改。将大鼠训练中从测试盒到达粒料一段十二天。训练期间后的试验可以应用于通过计数描述为食用粒料数目的成功率来测量复杂把持行为。本文介绍了在楼梯框中细致的培训，以及两者的性能BEH在天真，帕金森病和脑深部刺激条件avioral测试。

<table><tbody><tr><td>Staircase box without lid</td><td>Glas Keil, Germany</td><td></td><td>custom made</td></tr><tr><td>Cylinder box</td><td>Glas Keil, Germany</td><td></td><td>custom made</td></tr><tr><td>Dustless precision pellets, 45 mg</td><td>Bio Serv</td><td>F0021</td><td></td></tr></tbody></table>

a novel approach to assess motor outcome of deep brain stimulation effects in the hemiparkinsonian rat: staircase and cylinder test

底丘脑核的脑深部刺激为帕金森氏病的有效治疗选择。在我们的实验室，我们建立了一个协议，帕金森病（单侧损毁）大鼠筛选不同的神经刺激的模式。它包括通过在电缆结合外部神经刺激的24小时周期结束时注入6-羟基多巴胺（6-OHDA）入右内侧前脑束，植入慢性刺激电极插入底丘脑核和评估马达结果创建单方面帕金森病变。刺激用恒定电流刺激进行。的振幅低于副作用个体阈值为20％。马达结果评估是由气缸测试自发爪子使用的评估根据Shallert和熟练达到在根据蒙托亚楼梯测试评估完成。该协议中详细描述了楼梯框中训练中，Cylinder测试，以及在帕金森病大鼠同时使用的。使用两个测试是必要的，因为在楼梯测试似乎是精细运动技能障碍更敏感并且显示出更高的敏感性神经刺激期间改变。单方面帕金森模型和两个行为测试的组合允许不同的刺激参数的以标准化方式的评估。

所有动物都进行了多巴胺病变和电极位置的验尸组织学检验。只用在STN内正确的电极放置（ 图6）和完整多巴胺病变（&gt;在黑质多巴胺能神经元的90％的损失）动物被纳入结果部分（ 图7）。 损伤的条件下进行的圆柱体试验表明，损伤左爪子使用从约50％（天真的，健康的老鼠）减少到15.11％（平均）?...

Watch this Scientific Journal Video about A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test at JoVE.com

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

一种新的方法，以评估在帕金森病大鼠脑深部电刺激效应的运动结果:楼梯和缸测试

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

a-novel-approach-to-assess-motor-outcome-deep-brain-stimulation

Research

JoVE Journal

Behavior

14.6K 次观看.  University Hospital Wuerzburg. Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

视频: A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and 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

Assessing Forelimb Function after Unilateral Cervical SCI using Novel Tasks: Limb Step-alternation, Postural Instability and Pasta Handling

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI.

Three new behavioral tests (forelimb step-alternation, postural instability test, pasta handling test) for evaluating forelimb function after cervical spinal cord injury in rodents are described.

采用新型任务评估前肢功能单侧颈脊髓损伤后：肢体步交替，姿势不稳和面食处理

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority ...

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

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 by rearing and touching the walls of the cylinder with their forelimb paws for postural support. Following ischemic injury to the forelimb sensorimotor cortex, rats rely more heavily on their unaffected forelimb paw for postural support resulting in fewer touches with their affected paw which is termed forelimb asymmetry. In contrast, focal ischemic damage in the mouse brain fails to result in comparable consistent deficits in forelimb asymmetry. While forelimb asymmetry deficits are infrequently observed, mice do demonstrate a novel behaviour post stroke termed &#8220;paw-dragging&#8221;. Paw-dragging is the tendency for a mouse to drag its affected paw along the cylinder wall rather than directly push off from the wall when dismounting from a rear to a four-legged stance. We have previously demonstrated that paw-dragging behaviour is highly sensitive to small cortical ischemic injuries to the forelimb motor cortex. Here we provide a detailed protocol for paw-dragging analysis. We define what a paw-drag is and demonstrate how to quantify paw-dragging behaviour. The cylinder test is a simple and inexpensive test to administer and does not require pre-training or food deprivation strategies. In using paw-dragging analysis with the cylinder test, it fills a niche for predicting cortical ischemic injuries such as photothrombosis and Endothelin-1 (ET-1)-induced ischemia &#8211; two models that are ever-increasing in popularity and produce smaller focal injuries than middle cerebral artery occlusion. Finally, measuring paw-dragging behaviour in the cylinder test will allow studies of functional recovery after cortical injury using a wide cohort of transgenic mouse strains where previous forelimb asymmetry analysis has failed to detect consistent deficits.

Classical forelimb asymmetry analysis of the cylinder test is routinely used to assess behavioural deficits in rats following brain injury or stroke; however, it fails to detect consistent deficits in mice. This study demonstrates that quantifying paw-dragging behaviour is a more sensitive analysis of brain injury in mice.

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 ...

Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion

Behavioral assays are commonly used for the assessment of sensorimotor impairment in the central nervous system (CNS). The most sophisticated methods for quantifying locomotor deficits in rodents is to measure minute disturbances of unconstrained gait overground (e.g., manual BBB score or automated CatWalk). However, cortical inputs are not required for the generation of basic locomotion produced by the spinal central pattern generator (CPG). Thus, unconstrained walking tasks test locomotor deficits due to motor cortical impairment only indirectly. In this study, we propose a novel, precise foot-placement locomotor task that evaluates cortical inputs to the spinal CPG. An instrumented peg-way was used to impose symmetrical and asymmetrical locomotor tasks mimicking lateralized movement deficits. We demonstrate that shifts from equidistant inter-stride lengths of 20% produce changes in the forelimb stance phase characteristics during locomotion with preferred stride length. Furthermore, we propose that the asymmetric walkway allows for measurements of behavioral outcomes produced by cortical control signals. These measures are relevant for the assessment of impairment after cortical damage.

Here, we present a protocol to quantify precise stepping in rodents. Cortical and the spinal central pattern generator signals are required for precise foot-placement during obstructed locomotion. We report here the novel constrained walking task that directly examines precise stepping behavior.

非对称走道:一种新的行为检测方法的研究不对称步态

Behavioral assays are commonly used for the assessment of sensorimotor impairment in the central nervous system (CNS). The most sophisticated methods for ...

A Novel Single Animal Motor Function Tracking System Using Simple, Readily Available Software

We have recently demonstrated that implanting intracortical microelectrodes in the motor corteces of rats&#160;results in immediate and lasting motor deficits. Motor impairments were manually quantified through an open field grid test to measure the gross motor function and through a ladder test to measure the fine motor function. Here, we discuss a technique for the automated quantification of the video-recorded tests using our custom Capadona Behavioral Video Analysis System: Grid and Ladder Test, or BVAS. Leveraging simple and readily available coding software (see the Table of Materials), this program allows for the tracking of a single animal on both the open field grid and the ladder tests. In open field grid tracking, the code thresholds the video for intensity, tracks the position of the rat over the 3 min duration of the grid test, and analyzes the path. It then computes and returns measurements for the total distance traveled, the maximum velocity achieved, the number of left- and right-handed turns, and the total number of grid lines crossed by the rat. In ladder tracking, the code again thresholds the video for intensity, tracks the movement of the rat across the ladder, and returns calculated measurements including the time it took the rat to cross the ladder, the number of paw slips occurring below the plane of the ladder rungs, and the incidence of failures due to stagnation or reversals. We envision that the BVAS developed here can be employed for the analysis of motor function in a variety of applications, including many injury or disease models.

The current study aimed to automate the quantification of motor deficits in rats. The initial evaluation model assesses motor loss resulting from an intracortical microelectrode implantation in the motor cortex. We report on the development and use of a tracking algorithm using easily adaptable, simple, and readily available coding software.

一种新的单动物运动功能跟踪系统, 使用简单、易于使用的软件

We have recently demonstrated that implanting intracortical microelectrodes in the motor corteces of rats&#160;results in immediate and lasting motor ...

Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and dementia. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can lead to some Parkinson&#8217;s-like symptoms by destroying dopaminergic neurons in the substantia nigra of the brain. It has been thus used to establish PD models in various animal studies. Here, mice receive MPTP injections (20 mg/kg/day) for seven days and the behavioral tests are performed on the eighth day. This model is adapted efficiently in the study of PD. The behavioral tests here include the cylinder test and the open field test. The cylinder experiment is used to detect the animals&#8217; ability to lift their front paws when put into a different environment. As the PD model mice show arching&#8212;the mouse arches its back&#8212;the number of paw liftings decrease. This test is easy to execute. The open field test is used to detect the amount of time the mice spend on running, walking, and remaining immobile. We analyze animals&#8217; movements in open field using software and obtain data. Lastly, we use L-DOPA, one of the most commonly used PD drugs, as one example to show how to apply this model to the study of PD drugs. Our results indicate that MPTP neurotoxicity induces motor deficit which can be mitigated by L-DOPA.

We describe establishment of a murine model for Parkinson's disease using MPTP, and behavioral assessments using cylinder and open field tests to measure motor function. We then use L-DOPA as one example to show how to apply this model in the study of PD drugs.

小鼠 mptp 诱导的帕金森病模型中自发性运动的行为评估

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and ...

Unilateral Pyramidotomy of the Corticospinal Tract in Rats for Assessment of Neuroplasticity-inducing Therapies

The corticospinal tract (CST) can be completely severed unilaterally in the medullary pyramids of the rodent brainstem. The CST is a motor tract that has great importance for distal muscle control in humans and, to a lesser extent, in rodents. A unilateral cut of one pyramid results in loss of CST innervation of the spinal cord mainly on the contralateral side of the spinal cord leading to transient motor disability in the forelimbs and sustained loss of dexterity. Ipsilateral projections of the corticospinal tract are minor. We have refined our surgical method to increase the chances of lesion completeness. We describe postsurgical care. Deficits on the Montoya staircase pellet reaching test and the horizontal ladder test shown here are detected up to 8 weeks postinjury. Deficits on the cylinder rearing test are only detected transiently. Therefore, the cylinder test may only be suitable for detection of short term recovery. We show how, electrophysiologically and anatomically, one may assess lesions and plastic changes. We also describe how to analyse fibers from the uninjured CST sprouting across the midline into the deprived areas. It is challenging to obtain &#62;90% complete lesions consistently due to the proximity to the basilar artery in the medulla oblongata and survival rates can be low. Alternative surgical approaches and behavioural testing are described in this protocol. The pyramidotomy model is a good tool for assessing neuroplasticity-inducing treatments, which increase sprouting of intact fibers after injury.

The corticospinal tract, one of the major sensorimotor tracts, can be lesioned unilaterally in the rodent brainstem in order to test neuroplasticity-inducing therapies for the central nervous system. This surgical procedure (&#8220;pyramidotomy&#8221;) and postoperative assessments are described in this protocol.

皮质脊髓束的大鼠单侧锥体束的神经可塑性诱导疗法的评估

The corticospinal tract (CST) can be completely severed unilaterally in the medullary pyramids of the rodent brainstem. The CST is a motor tract that has ...

神经科学

Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk factor for AD, stroke has also been implicated as a risk factor and an exacerbating factor. The co-morbidity of stroke and AD results in worsened stroke-related motor control and AD-related cognitive deficits when compared to each condition alone. To model the combined condition of stroke and AD, a novel transgenic rat model of AD, with a mutated form of amyloid precursor protein (a key protein involved in the development of AD) incorporated into its DNA, is given a small unilateral striatal stroke.
For a model with the combination of both stroke and AD, behavioral tests that assess stroke-related motor control, locomotion and AD-related cognitive function must be implemented. The cylinder task involves a cost-efficient, multipurpose apparatus that assesses spontaneous forelimb motor use. In this task, a rat is placed in a cylindrical apparatus, where the rat will spontaneously rear and contact the wall of the cylinder with its forelimbs. These contacts are considered forelimb motor use and quantified during video analysis after testing. Another cost-efficient motor task implemented is the beam-walk task, which assesses forelimb control, hindlimb control and locomotion. This task involves a rat walking across a wooden beam allowing for the assessment of limb motor control through analysis of forelimb slips, hindlimb slips and falls. Assessment of learning and memory is completed with Morris water maze for this behavioral paradigm. The protocol starts with spatial learning, whereby the rat locates a stationary hidden platform. After spatial learning, the platform is removed and both short-term and long-term spatial reference memory is assessed. All three of these tasks are sensitive to behavioral differences and completed within 28 days for this model, making this paradigm time-efficient and cost-efficient.

To investigate the co-morbid Alzheimer&#39;s disease (AD) and stroke condition in a novel model, three behavior tasks are described that assess both motor control and cognitive behaviors. These tasks include the beam-walk task, cylinder task and Morris water maze.

汽车和海马依赖空间学习和记忆参考评估与中风阿尔茨海默氏病的转基因大鼠模型

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk ...

医学

Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes demonstrate the ability to record action potentials from individual or small groups of neurons. Such recorded signals have successfully been used to allow patients to interface with or control&#160;computers, robotic limbs, and their own limbs. However, previous animal studies have shown that a microelectrode implantation in the brain not only damages the surrounding tissue but can also result in functional deficits. Here, we discuss a series of behavioral tests to quantify potential motor impairments following the implantation of intracortical microelectrodes into the motor cortex of a rat. The methods for open field grid, ladder crossing, and grip strength testing provide valuable information regarding the potential complications resulting from a microelectrode implantation. The results of the behavioral testing are correlated with endpoint histology, providing additional information on the pathological outcomes and impacts of this procedure on the adjacent tissue.

We have shown that a microelectrode implantation in the motor cortex of rats causes immediate and lasting motor deficits. The methods proposed herein outline a microelectrode implantation surgery and three rodent behavioral tasks to elucidate potential changes in the fine or gross motor function due to implantation-caused damage to the motor cortex.

大鼠运动皮质微电极植入所致功能缺损的啮齿动物行为检测

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes ...

生物工程

The Mouse Stroke Unit Protocol with Standardized Neurological Scoring for Translational Mouse Stroke Studies

The filament model of middle artery occlusion (fMCAo) is perhaps the most translational mouse stroke model, allowing for controlled ischemia with intravascular reperfusion/recanalization. However, it lacks alignment with current clinical advances for stroke care (e.g., Stroke Units), usually employs subjective or vague neurological scoring among laboratories, and exhibits high acute-phase mortality. Here, we address these limitations with validated video-guided protocols. We present the mouse Stroke Unit (mSU) protocol with instructional videos and a decision algorithm (Risk Stratification Score), bridging the gap between clinical and mouse stroke modeling. To increase accuracy and sensitivity of stroke neurological scoring, we present for the first time a video-standardized format of the focal Experimental Stroke Scale (fESS) and prove its value up to 6 months post-stroke. Additionally, protocols for mice Ladder-rung test, as well as the known Cylinder test, for unbiased, quantitative assessment of limbs&#180; motor function are presented. Results highlight mSU&#39;s translational efficacy. Focal ESS (fESS) excels over other known scales in detecting focal stroke deficits, capturing recovery, and maintaining sensitivity for up to 6 months post-stroke. Ladder-rung and Cylinder tests objectively quantify and monitor fore- and hind-limb motor deficits, long-term. In summary, integrating mSU, fESS, and motor function tests provides a robust framework for clinically relevant stroke investigations. Our protocols improve the translational value in mouse stroke research.

This article presents a protocol for executing the highly translational and independently proven mouse Stroke Unit (mSU) concept in large-stroke mice. It also provides a standardized protocol for executing the focal experimental stroke scale in mice, which evaluates stroke focal deficits detected even long-term.