Name: neurodevelopmental reflex testing in neonatal rat pups
Uploaded: 2017-04-24T14:00:00.000+00:00
Duration: 9 min 35 s
Description: Watch this Scientific Journal Video about Neurodevelopmental Reflex Testing in Neonatal Rat Pups at JoVE.com

作者要感谢我们的资助机构，其中包括NeuroDevNet（卓越的国家中心），将ALVA基金会，妇女和儿童健康研究所和艾伯塔大学。

动物护理和使用委员会，健康科学阿尔伯塔大学批准了所有动物研究。 注意:虽然此协议可以适用于其他物种和品系，该协议是为Long-Evans大鼠写的。这些大鼠已经显示出具有相对于其他啮齿动物品系优越马达性能和视觉敏锐度。 25，26，用于定时怀孕，膳食补充，产妇炎症，和神经发育反射的协议如下。 1.实验动物<ol><li>当大鼠到达动物住房设施，从一天或两天的任何交互不要让他们适应新的环境。继习服，每天处理的老鼠大约五天，或者当老鼠不再显示压力的迹象。人类引起的压力可以改变测试结果和乐广告流产。 </li><li>一旦老鼠是舒适，养殖开始。放置两个女性和在双层养殖笼一个雄性大鼠（H = 38厘米，1800厘米2面积）过夜（3 PM -上午08点）。这些笼预防应激和拥挤。在早晨，用移液管，冲洗雌性大鼠用大约0.25毫升盐水阴道。将溶液转移到一个离心管中。 </li><li>两个女性和男性放回各自的传统笼养。 </li><li>查看在光学显微镜（100倍）下在1.2节中收集的溶液，以确定将大鼠经历其发情周期的阶段，以及是否精子都存在。如果有精子，记录日期为胚胎天（E1）（ 图1）。如果怀孕，给女性她自己在E14的笼子。 注意:在阴道涂片细胞是明确的，因此使用低光设置。确保冷凝器被调整到它的最低值。广告只是亮度控制调暗的光。如果亮度旋钮可用，将其设置为1。 </li></ol> 2.早期断奶仔猪注:此协议旨在最后一周怀孕，以评估饮食椰菜芽消费的治疗效果。据吴某等人成长的豆芽。 27。 <ol><li>浸泡花椰菜芽种子2 - 3小时。传播种子出在工作台面上种子sprouter盒和上发芽温暖表面设置。 </li><li>水的种子，每天两次，一次是在AM（8 - 上午09点），一次在下午（3 - 下午4点）。 </li><li>在第五天，通过一天的窗口放置豆芽（豆芽应该各有两片叶子，将成为绿色在一天）。 </li><li>在一天结束时，通过轻轻地拉动花椰菜芽出筛分箱的收获豆芽打下在平坦表面上干燥。 </li><li>一旦豆芽被完全干燥，瓦特eigh出200毫克，并装在密封的塑料袋中。 </li><li>自E14，每日饲料每妊娠大鼠200mg的干燥花椰菜芽，直到PD21（一天幼仔断奶）。 </li></ol> 3.炎症<ol><li>诱发炎症和后代繁殖白质损伤，与脂多糖（LPS）的E19和E20每12小时注入孕鼠。在注射的当天，把笼到从住房设施的实验室。允许孕鼠驯化和变得冷静至少1小时。如果老鼠显示出永久的全身性或肾损害的临床症状，将立即实施安乐死，并从研究中移除。 </li><li>称量怀孕水坝。 </li><li>溶解200微克/千克的LPS（血清型0127:B8）在100μL生理盐水。吸出溶液到装有30 G½针1mL注射器。 <ol><li>使用新针，每次注射。使溶液预热几分钟，以尽量减少不适。 </LI&gt; </ol></li><li>记录的时间和腹腔注射孕大坝。侧之间交替注射，以确保均匀分布。 注:Machholz 等。讲解了正确的克制和注射过程。 28 </li></ol> 4.发展反射测试<ol><li>在PD1（出生日期），请从大坝和记录出生体重的幼崽。将幼仔放回各自的笼子里，它们移动到动物设施，直到PD3。这确保水坝和小狗之间母体接合。 <ol><li>记录了可靠的评估复检。调整视频摄像机，以便它处于最大快门速度以一帧一帧的分析（1 / 1,000或多个）。使得其正上方或大鼠幼仔和用于每个反射所有材料旁边的摄像机位置。例如，对于后肢放置，放置相机大鼠幼崽的旁边，以保证提升和后肢放置被捕获。 </li><li>对于加速扶正，将老鼠的小狗和着陆垫上面的摄像头，以记录小狗在半空中权的能力。 </li></ol></li><li>每天记录的权重，直到实验结束。上PD3，开始神经发育反射测试（ 图4）。移动笼成一个安静的房间最少测试前1个小时，以允许适应于环境。 </li><li>在一致的时间，每天进行神经反射测试，大鼠是夜行动物。例如，上午09点之间的测试 - 每日下午12点。保持幼仔直属加热灯或在散热垫在所有时间，以维持稳定的体温为36.5℃;这个年龄段的幼鼠很容易失去的热量。用直肠温度探头测量。如果有效地完成，仔兔体温不改变，因为他们没有从大坝和枯枝落叶足够长的时间删除。注:监视热灯的温度，以确保其不超过37℃。 <ol&gt; <li>记录每一个反射的分数每一天直到肯定响应是观察。当小狗能连续两天执行任务时，会发生积极的反射反应。的积极响应的第一次出现的日期用于定量。没有进一步检测后的积极响应。因此，结束日期为每个反射是可变的。 </li></ol></li><li> 前肢抓 <ol><li>开始在PD3，进行前肢握持反射测试。放置一个钝杆针对各前爪的手掌和手动应用光压力。光压力应稍移位前爪，确保接触时和幼崽能感觉到杆。抓会作为在该棒所有数字屈曲。当两个前爪抓住棒连续2天成功收购这种反射的发生。 </li><li>分数前肢把握: 0为不抓 1用于由一个前爪成功把持（左或r飞行前爪可以在这里指定） 2，通过这两个前爪抓成功</li></ol></li><li> 后肢抓 <ol><li>开始在PD3，进行后肢握反射测试。放置一个钝杆对每个后爪的鞋底和手动应用光压力。光压力应该稍微移动后爪，确保接触时和幼崽能感觉到杆。杆成功抓取出现的绕杆数字屈曲。当两只后爪抓住棒连续2天成功收购这种反射的发生。 </li><li>分数后肢把握: 0为不抓 1成功把持由一个后爪（左或可以在这里指定右后爪） 2，通过两只后爪抓成功</li></ol></li><li> 扶正 <ol><li>开始在PD3，开始翻正反射测试。牢牢把握在仰卧位的小狗，用四只爪子直立。放开ØF中的小狗，并立即开始计时。当小狗能够翻转/翻转到所有四只爪实现扶正，并且每个爪是垂直于本体。给每个小狗最多的15秒来实现这一目标。 </li><li>分数扶正: 0仰卧（或15秒的最大分配的时间） 1侧卧（左侧或右侧可以在这里指定）或小狗的右，但在错误的姿势（或15秒的最大分配时间的能力） 2成功扶正和适当的姿势</li></ol></li><li> 配售后肢 <ol><li>开始在PD4，开始后肢放置反射试验。垂直握住小狗在空中，由躯干。轻轻中风后爪的背部用钝表面（诸如桌子的边缘）。正确的放置反射是当大鼠幼仔撤回刺激后肢，随后向下后肢在该表面上的放置。 </li><li>分数后肢PLacing反射: 0为不成就 1为一个后爪的放置（左或可以在这里指定右后爪） 2成功后肢放置于两个后爪</li></ol></li><li> 悬崖回避 <ol><li>开始在PD4，开始了悬崖回避测试。放置大鼠幼仔在平坦表面的边缘，使得所述小狗的前爪和口鼻部是在边缘。正确的结果是一种保护性反应，其中，所述大鼠幼鼠从悬崖的边缘却步。实验者的手或泡沫着陆被放置在悬崖下方，以赶上从秋季小狗。 </li><li>分数悬崖回避: 0表示无运动或脱落的边缘 1对试图摆脱悬崖走，但有四肢挂 2成功的运动从悬崖上掉</li></ol></li><li> 步态 <ol><li>开始步态对PD6评价。在15厘米的diamet的中心地点幼仔呃圈，让小狗30秒完成任务。当大鼠幼崽能够在少于30秒移动至圆的外侧既前爪进行14成功的步态。 </li><li>分数步态以秒所花费的老鼠的小狗外循环移动所需的时间。记录花费的小狗移动圈外两个前爪的时间。记录30秒，如果幼犬无法在规定时间内完成任务</li></ol></li><li> 听觉惊吓 <ol><li>开始在PD10听觉惊吓的分析。呈现巨响（钟形）直接在小狗评估惊愕反应是否存在。当小狗显示"抽搐"移动，从声音远观察到的正的惊恐反应。 </li><li>分数听觉惊吓: （或没有）为无惊恐反应 （或者是）对于正惊恐反应</li></ol></li><li> 姿势 <ol><li>开始对PD态势分析12.在非滑开表面地点幼仔，观察移动时小狗具有姿势。不成熟的姿态由移动时腹部，并相对于主体二者前爪和后爪的垂直指向的拖动反射。一个成熟的姿势被获取时小狗可以从表面抬起腹部和两个前爪和后爪，指出直的或平行于主体，移动时。 </li><li>分数姿势: 0为不运动 移动时1未成熟姿势 2为成熟的姿势而移动</li></ol></li><li> 眼开 <ol><li>开始在PD12大开眼界的分析。记录当天两眼皮开: 0为不可见的眼睛 1为一个可见的眼睛（左或右侧可以在这里指定） 2两个可见的眼睛</li></ol></li><li> 加速正位 <ol><li>开始于PD14，开始加速测试扶正。将小狗在仰卧位30.48Çentimeters上述泡沫着陆。掉落的小狗，并观察其对权利本身的能力。扶正是指当小狗能翻身俯卧位和土地上它的爪子。 </li><li>分数加速扶正: 0落在它的后面 1坠落在其一侧（左侧或右侧可以在这里指定） 2登陆它的爪子</li></ol></li></ol>注:不同类型的反射的定量可根据研究者的问题。该反射的量化可以作为一种条件反射的初步观察，外观起来的第一天，直到反射消失，花费的时间成功地完成了任务，性能速度，和/或随着时间的性能改进来完成。 13，14，29，30，31为Current研究中，外观的第一天作为一个得分。当使用多子模型，来自同一窝幼仔通常的行为类似，由于他们的基因构成， 在子宫内和产后的环境和营养的可用性。 32因此，单个小狗不能占作为n = 1，由于垫料偏压。一窝内检查幼仔可以被平均，使得每个窝表示n = 1。 32，33可替换地，同窝内的几个幼仔可以使用混合效应模型，其中考虑到幼仔同一窝内进行分析。 32，33

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神经反射测试是不正常的皮质发育和成熟的预测指标，这可能是情况下，其中明显的神经病理学并不明显意义。在神经发育测试，关键是要确保幼崽在同一时间每天检查。鼠是夜间活动，因此，如果测试是在一天中的不同时间执行他们的昼夜节律可能会改变性能。 34测试应在安静的房间内完成为大声喧哗，可以加应力的幼崽。 35只幼仔需要至少1个小时，以适应...

神经反射，或发展的里程碑，是对人类新生儿和婴儿最早使用的评估项目之一。神经反射是展示脑干和脊髓反射不由自主的和重复的动作。更高皮质网络，其特征在于演进迁移，髓鞘形成，和突触的成熟促进自愿控制和皮质抑制。在中枢神经系统演进的正常进展的改变可以破坏大脑发育，产生异常皮质布线，功能，和髓鞘形成，神经发育造成反射延迟或缺席。在神经发育残疾的高风险与人婴儿通常表现出异常的早期反射。反射异常可呈现在采集，不存在延迟，延长的存在，或再现以后的生活中，并且预测发育障碍的。 1，2因此，它模仿神经发育障碍的实验模型反射延迟是很重要的。 鼠害通常用作实验模型。出生的时候幼鼠是altricial，因此太不成熟承担具体的或复杂的运动，感觉和/或认知行为的任务。在这方面，他们的发育不成熟同时涉及他们的身体和器官的发育。老鼠是天生无毛为不能thermoregulate，是盲目的，无法行走。参照大脑发育，皮质相当成熟出生后发生。新生大鼠幼崽（出生当天称为1日龄; PD1）已经被建议以达到脑成熟水平是类似于23早产人脑 - 妊娠28周，而PD7-10幼仔相当于近长期人类的大脑。 3，4，5，6这种相关性是基于大体解剖分析，但是，如髓鞘形成和振幅整合脑电图脑成熟的其他措施也已经被描述。 5,7例如，预少突胶质细胞是主要的细胞在发展人胎脑从23 - 宫内 32周，这的成熟阶段对应于PD1-3啮齿动物。 5，8，9，10此外，髓鞘形成开始于宫内在人类中，而在大鼠幼仔它出现在周围PD7-10前脑;在新生啮齿动物脑在很大程度上仍然未髓。 11，12 Tucker 等。发现，P1大鼠的振幅整合脑电图图案为类似于一个23周gesta重刑人类胎儿，而PD7和PD10小狗是类似于一个30 - 52周和足月儿，分别。 7出于这些原因，在新生幼鼠新生儿反射测试提供了捕获个体发育和/或大脑发育受阻的机会。 下面描述反射的电池适于从由姆·福克斯和A. Lubics 13,14 WM福克斯相对于在小鼠反射的个体发育的最早研究者之一的研究。 13个这些反射包括，但不限于，四肢抓握和放置，悬崖回避，扶正，加速扶正，步态，听觉惊跳，姿势，和眼图张度。两个前肢及后肢把握（分别被称为人类掌跖把握，）由脊髓反射和从非主运动区皮质抑制变得容易。 15,16后肢放置（跖反射）反映皮质脊髓束的成熟。 16，17，18崖避免（保护反应），扶正（迷宫），以及加速扶正涉及感觉输入和电动机输出之间的集成和通信（例如，那些涉及触须和前庭系统）。 19，20，21步态体现运动。 14听觉惊跳评估声刺激和巨神经元的突触连接在细胞核脑桥网状尾。 21姿势涉及适当皮质脊髓/脊柱皮质突起，肌肉力量，和神经肌肉的神经支配。 22，23马伽马氨基丁酸受体turation可与眼图张度相关。 24重要的是要记住的是，反射反映一个更复杂的网络，在这里提供的是一般的关系是非常重要的。此外，这些反射提供在非常年轻的时候在那里更复杂的行为测试是不可行的评价神经发育的快速简便的方法。 本文的目的是提供一种可以很容易地纳入实验新生大鼠研究神经发育复检的一般准则。描述的方法是在长埃文斯新生幼鼠进行和结果的定量是基于外观的第一天。该反射测试当天被启动，并且使用的设备可以被修改以更好地适应不同的实验模型（例如用于不同菌株和物种）。通过建立ref的正常生理进展在一个特定的动物模型成熟法，调查员可以评估外部应激物，内源性的操作，和/或在新生大鼠的神经发育的治疗性干预的效果。总体而言，使用反射的脑成熟的确定是在预测围产期脑损伤有利的，并且是后面反射神经发育结局的。

<table><tbody><tr><td>&lt;em&gt;Breeding&lt;/em&gt;</td><td></td><td></td><td></td></tr><tr><td>Transfer pipettes</td><td>Fisherbrand</td><td>12-711-9AM</td><td>Used for vaginal flushes.</td></tr><tr><td>Sterile Saline</td><td>Hospira</td><td>7983254</td><td>The solution used to collect cells during vaginal flushes.</td></tr><tr><td>400 &amp;micro;L Microcentrifuge tubes</td><td>Fisherbrand</td><td>05-408-120</td><td>Used to hold the saline solution.</td></tr><tr><td>Light microscope</td><td>Leica</td><td>Leica ATC 2000</td><td>For observation of the saline solution. Can be any light microscope used in the lab.</td></tr><tr><td>Slides</td><td>Fisherbrand</td><td>12-552-5</td><td>The saline solution is placed on the slide. Can be any slides used in the lab.</td></tr><tr><td>Coverslips</td><td>Fisherbrand</td><td>12-545-F</td><td>To coverslip the slides. Can use any coverslips used in the lab.</td></tr><tr><td>&lt;em&gt;Dietary&amp;nbsp; Supplementation&lt;/em&gt;</td><td></td><td></td><td></td></tr><tr><td>Broccoli Sprouts seeds</td><td>Mumm&#039;s Sprouting Seeds</td><td></td><td>Broccoli sprouts seeds are ordered and grown in the lab.</td></tr><tr><td>Countertop Seed Sprouter Box</td><td>Mumm&#039;s Sprouting Seeds</td><td></td><td>A box is used to germinate and grow the seeds prior to harvest.</td></tr><tr><td>250 mL beaker</td><td></td><td></td><td>The beaker is used to soak the seed. Any size beaker that would fit can be used.</td></tr><tr><td>&lt;em&gt;Maternal Inflammation&lt;/em&gt;</td><td></td><td></td><td></td></tr><tr><td>Lipoplysaccharide (LPS)</td><td>Sigma</td><td>L3129</td><td>The endotoxin used to mimic maternal inflammation.</td></tr><tr><td>1 mL Syringe</td><td>BD Syringe</td><td>309659</td><td>Used to inject the pregnant rat.</td></tr><tr><td>Gauge (30 G x 1/2)</td><td>BD PrecisionGlide Needle</td><td>305106</td><td>Use the smallest needle to avoid pain and discomfort.</td></tr><tr><td>Sterile Saline (0.9% Sodium Chloride, USP)</td><td>Hospira</td><td></td><td>Saline is used to dissolve LPS.</td></tr><tr><td>&lt;em&gt;Weights&lt;/em&gt;</td><td></td><td></td><td></td></tr><tr><td>Scale</td><td>Denver Instrument</td><td></td><td>For recording the weights. Can be any scale with 2 decimal places used in the lab.</td></tr><tr><td>&lt;em&gt;Neurodevelopmental Reflexes&lt;/em&gt;</td><td></td><td></td><td></td></tr><tr><td>Thin blunt rod</td><td></td><td></td><td>Can be a paperclip or toothpick. This is for forelimb and hindlimb grasping.</td></tr><tr><td>Round filter paper</td><td>Whatman</td><td>1001 150</td><td>15 cm diameter paper used for gait analysis.</td></tr><tr><td>Timer</td><td>Fisher Scientific</td><td>06-662-51</td><td>For timing the time allocated to righting and gait.</td></tr><tr><td>Blunt surface</td><td></td><td></td><td>Can be an edge of a table. This is for hindlimb placing and cliff avoidance.</td></tr><tr><td>Foam landing</td><td></td><td></td><td>For when the pups perform accelerated righting.</td></tr><tr><td>Video recorder</td><td>Sony</td><td>VCT-D580RM</td><td>To record all reflexes tested. Must be able to record at 1/1,000 fps</td></tr><tr><td>Bell</td><td></td><td></td><td>For auditory startle.&amp;nbsp;</td></tr><tr><td>Heat lamp or pad</td><td></td><td></td><td>To maintain the body temperature of the pups underoing examination.</td></tr></tbody></table>

neurodevelopmental reflex testing in neonatal rat pups

神经发育反射测试是在临床实践中通常使用的，以评估中枢神经系统的成熟。神经反射也被称为原始反射。他们是敏感的，并与后来的结果是一致的。反射异常被描述为不存在，持久性，再现，或延迟反射，其是处于对神经发育障碍的高风险的婴儿的预测指标。神经发育障碍，如脑瘫的动物模型，通常表现出发育异常反射，如将人类婴儿进行观察。所描述的技术评估各种新生大鼠神经发育反射的。神经反射测试提供了研究者的测试方法，是不是在如此年轻的动物，否则可用。这里介绍的方法，目的是协助调查人员在审查新生大鼠的发育里程碑检测早发BR的方法AIN损伤和/或确定治疗性干预的有效性。这里介绍的方法，目的是为研究者提供的一般准则。

本实验设计的时间轴示于图2。 30种的方法和结果之前已公布。 30本研究的目的是评估膳食补充妊娠期间花椰菜芽和断奶前周期是否保护， 在子宫内暴露于LPS诱导的神经发育由延迟的后代。定时怀孕的大鼠给予生理盐水（对照组，100μL）或LPS（200微克/千克在100μL无菌生理盐水稀释）上E19和E20每12小?...

Watch this Scientific Journal Video about Neurodevelopmental Reflex Testing in Neonatal Rat Pups at JoVE.com

Neurodevelopmental Reflex Testing in Neonatal Rat Pups

行为测试是确定脑损伤后的结果的黄金标准，并可以识别发育障碍的婴儿和儿童的存在。神经反射是这些异常的早期指标。在新生儿啮齿动物很容易地完成发育反射测试的主机进行了开发和说明。

神经发育复检新生幼鼠

Neurodevelopmental reflex testing is commonly used in clinical practice to assess the maturation of the nervous system. Neurodevelopmental reflexes are ...

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Behavior

19.7K 次观看.  University of Alberta. 行为测试是确定脑损伤后的结果的黄金标准，并可以识别发育障碍的婴儿和儿童的存在。神经反射是这些异常的早期指标。在新生儿啮齿动物很容易地完成发育反射测试的主机进行了开发和说明。 

视频: Neurodevelopmental Reflex Testing in Neonatal Rat Pups

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.

The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. The purpose of this article is to describe the NNNS, provide video examples of the NNNS procedures and discuss the ways in which the exam has been used.

评估和高危新生儿的评价：新生儿重症监护病房的网络神经行为量表

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant.  The NICU Network Neurobehavioral Scale ...

科研

行为学

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, few studies have investigated the long-term effects of injury in rodent models of TBI. Shown here are behavioral measures that are well-established in TBI research for times early after injury, such as two weeks, until two months. Some of these methods have previously been used at later times after injury, up to one year, but by very few laboratories. The methods demonstrated here are a short neurological assessment to test reflexes, a Beam-Balance to test balance, a Beam-Walk to test balance and motor coordination, and a working memory version of the Morris water maze that can be sensitive to deficits in reference memory. Male rats were handled and pre-trained to neurological, balance, and motor coordination tests prior to receiving parasagittal fluid percussion injury (FPI) or sham injury. Rats can be tested on the short neurological assessment (neuroscore), the beam-balance, and the Beam-Walk multiple times, while testing on the water maze can only be done once. This difference is because rats can remember the task, thus confounding the results if repeated testing is attempted in the same animal. When testing from one to three days after injury, significant differences are detected in all three non-cognitive tasks. However, differences in the Beam-Walk task were not detectable at later time points (after 3 months). Deficits were detected at 3 months in the Beam-Balance and at 6 months in the neuroscore. Deficits in working memory were detected out to 12 months after injury, and a deficit in a reference memory first appeared at 12 months. Thus, standard behavioral tests can be useful measures of persistent behavioral deficits after FPI.

The goal of the behavioral tests presented here is to detect functional deficits in rats after traumatic brain injury. Four specific tests are presented that detect deficits in behaviors to reflect the damage to specific brain areas at times extending to one year after injury.

颅脑损伤后大鼠行为缺陷的检测

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, ...

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 Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders

Neonatal rats were administered a relatively high concentration of ethyl alcohol (11.9% v/v) during postnatal days 4-9, a time when the fetal brain undergoes rapid organizational change and is similar to accelerated brain changes that occur during the third trimester in humans. This model of fetal alcohol spectrum disorders (FASDs) produces severe brain damage, mimicking the amount and pattern of binge-drinking that occurs in some pregnant alcoholic mothers. We describe the use of trace eyeblink classical conditioning (ECC), a higher-order variant of associative learning, to assess long-term hippocampal dysfunction that is typically seen in alcohol-exposed adult offspring. At 90 days of age, rodents were surgically prepared with recording and stimulating electrodes, which measured electromyographic (EMG) blink activity from the left eyelid muscle and delivered mild shock posterior to the left eye, respectively. After a 5 day recovery period, they underwent 6 sessions of trace ECC to determine associative learning differences between alcohol-exposed and control rats. Trace ECC is one of many possible ECC procedures that can be easily modified using the same equipment and software, so that different neural systems can be assessed. ECC procedures in general, can be used as diagnostic tools for detecting neural pathology in different brain systems and different conditions that insult the brain.

Trace eyeblink classical conditioning (ECC) was used to assess hippocampal-dependent associative learning in adult rats that were administered a high concentration (11.9% v/v) of alcohol during early neonatal brain development. In general, ECC procedures are sound diagnostic tools for detecting brain dysfunction across many psychological and biomedical settings.

使用的跟踪经典条件反射，评估胎儿酒精谱系障碍大鼠模型海马功能障碍

Neonatal rats were administered a relatively high concentration of ethyl alcohol (11.9% v/v) during postnatal days 4-9, a time when the fetal brain ...

神经科学

Recording EEG in Freely Moving Neonatal Rats Using a Novel Method

EEG is a useful method to detect electrical activity in the brain. Moreover, it is a widely used diagnostic tool for various neurological conditions, such as epilepsy and neurodegenerative disorders. However, it is technically difficult to obtain EEG recordings in neonates as it requires specialized handling and great care. Here, we present a novel method to record EEG in neonatal rat pups (P8-P15). We designed a simple and reliable electrode using computer pin loci; it can be easily implanted into the skull of a rat pup to record high-quality EEG signals in the normal and epileptic brain. Pups were given an intraperitoneal (i.p.) injection of the neurotoxin kainic acid (KA) to induce epileptic seizures. The surgical implantation performed in this procedure is less expensive than other EEG procedures for neonates. This method allows one to record high-quality and stable EEG signals for more than 1 week. Furthermore, this procedure can also be applied to adult rats and mice to study epilepsy or other neurological disorders.

Here, we introduce a novel technique designed to record electroencephalography (EEG) in freely moving neonatal epileptic pups and describe its procedures, features, and applications. This method allows one to record EEG for more than 1 week.

使用新颖的方法在自由移动的新生大鼠中记录脑电图

EEG is a useful method to detect electrical activity in the brain. Moreover, it is a widely used diagnostic tool for various neurological conditions, such ...

Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury

We performed unilateral carotid artery occlusion on CD-1 mice to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of neonatal HI brain injury by studying neurobehavioral functions in these mice compared to non-operated (i.e., normal) mice. During the study, Rice-Vannucci&#39;s method was used to induce neonatal HI brain damage in postnatal day 7-10 (P7-10) mice. The HI operation was performed on the pups by unilateral carotid artery ligation and exposure to hypoxia (8% O2 and 92% N2 for 90 min). One week after the operation, the damaged brains were evaluated with the naked eye through the semi-transparent skull and were categorized into subgroups based on the absence (&#34;no cortical injury&#34; group) or presence (&#34;cortical injury&#34; group) of cortical injury, such as a lesion in the right hemisphere. On week 6, the following neurobehavioral tests were performed to evaluate the cognitive and motor functions: passive avoidance task (PAT), ladder walking test, and grip strength test. These behavioral tests are helpful in determining the effects of neonatal HI brain injury and are used in other mouse models of neurodegenerative diseases. In this study, neonatal HI brain injury mice showed motor deficits that corresponded to right hemisphere damage. The behavioral test results are relevant to the deficits observed in human neonatal HI patients, such as cerebral palsy or neonatal stroke patients. In this study, a mouse model of neonatal HI brain injury was established and showed different degrees of motor deficits and cognitive impairment compared to non-operated mice. This work provides basic information on the HI mouse model. MRI images demonstrate the different phenotypes, separated according to the severity of brain damage by motor and cognitive tests.

We performed unilateral carotid artery occlusion on postnatal day 7-10 CD-1 mouse pups to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of HI brain injury. We studied neurobehavioral functions in these mice compared to non-operated normal mice.

小鼠新生儿缺氧缺血性脑损伤模型的神经行为评估

We performed unilateral carotid artery occlusion on CD-1 mice to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of neonatal HI ...

Electrophysiological Measurement of Noxious-evoked Brain Activity in Neonates Using a Flat-tip Probe Coupled to Electroencephalography

Pain is an unpleasant sensory and emotional experience. In non-verbal patients, it is very difficult to measure pain, even with pain assessment tools. Those tools are subjective or determine secondary physiological indicators which also have certain limitations particularly when exploring the effectiveness of analgesia. As cortical processing is essential for pain perception, brain activity measures may provide a useful approach to assess pain in infants. Here we present a method to assess nociception with electrophysiological brain activity recordings optimized for the use in newborn infants. To produce highly standardized and reproducible noxious stimuli we applied mechanical stimulation with a flat-tip probe, e.g., PinPrick, which is not skin-breaking and does not cause behavioral distress. The noxious-evoked potential allows the objective measurement of nociception in non-verbal patients. This method can be used in newborn infants as early as 34 weeks of gestational age. Moreover, it could be applied in different situations such as measuring the efficacy of analgesic or anesthetic drugs.

Measuring pain in non-verbal patients is a challenge. In this study we combine EEG recording with stimulation using a flat-tip probe to detect noxious-evoked brain activity in an objective manner.

应用平板探针结合脑电图对新生儿有害诱发脑活动的电生理测量

Pain is an unpleasant sensory and emotional experience. In non-verbal patients, it is very difficult to measure pain, even with pain assessment tools. ...

Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex

The concept of objective nociceptive assessment and optimal pain management have gained increasing attention. Despite the known negative short- and long-term consequences of unresolved pain or excessive analgosedation, adequate nociceptive monitoring remains challenging in non-communicative, critically ill adults. In the intensive care unit (ICU), routine nociceptive evaluation is carried out by the attending nurse using the Behavior Pain Scale (BPS) in mechanically ventilated patients. This assessment is limited by medication use (e.g., neuromuscular blocking agents) and the inherent subjective character of nociceptive evaluation by third parties.
Here, we describe the use of two nociceptive reflex testing devices as tools for objective pain evaluation: the pupillary dilation reflex (PDR) and nociception flexion reflex (NFR). These measurement tools are non-invasive and well tolerated, providing clinicians and researchers with objective information regarding two different nociceptive processing pathways: (1)&#160;the pain-related autonomic reactivity&#160;and (2) the ascending component of the somatosensory system. The use of PDR and NFR measurements are currently limited to specialized pain clinics and research institutions because of impressions that these are technically demanding or time-consuming procedures, or even because of a lack of knowledge regarding their existence.
By focusing on the two abovementioned nociceptive reflex assessments, this study evaluated their feasibility as a physiological pain measurement method in daily practice. Pursuing novel technologies for evaluating the analgesia level in unconscious patients may further improve individual pharmacological treatment and patient related outcome measures. Therefore, future research must include large well-designed clinical trials in a real-life environment.

Pain assessment in anesthetized patients who cannot communicate with the outside world in any way remains challenging despite the development of innovative objective pain evaluation tools. In this project, the pupillary dilation reflex and the nociception flexion reflex are assessed in critically ill, mechanically ventilated adult patients.

应用 Pupillometry 和伤害性屈曲反射的可行性研究--通气 ICU 患者的客观伤害评估

The concept of objective nociceptive assessment and optimal pain management have gained increasing attention. Despite the known negative short- and ...

Developmental Enhancement in Cerebral Palsy Rats via Spinal Manipulations

Enhancing the Development and Growth of Infant Cerebral Palsy Rats Using Selective Spinal Manipulations

Cerebral palsy (CP) is a refractory pediatric disease with a high prevalence, high disability rate, and difficult treatment. A variety of treatments are currently used for CP. The treatment involves drug and non-drug therapy. Traditional Chinese medicine external therapy is a very distinctive treatment method in non-drug therapy. As one of the external therapies of traditional Chinese medicine, massage is used in treating cerebral palsy and has good efficacy, small side effects, and strong operability. As a part of TCM external therapy, selective spinal manipulation can effectively promote the growth and development of infant rats with cerebral palsy.The operation was mainly divided into four steps: first, the rubbing method was applied to the spine and both sides of the spine for 1 min. The pressing and kneading method was applied to the spine for 5 min, and the muscles on both sides of the spine for 5 min. Second, pressing and kneading the sensitive local acupoints in the spine for 2 min were performed. Thirdly, the affected limb was treated by twisting method for 1 min. Fourth, the rubbing method was applied to a midline from the forehead to the back of the brain for 1 min. This study aimed to use selective spinal manipulation to treat infant rats with cerebral palsy. The weight, Rotarod test, Foot-fault score, and growth hormone of infant rats with cerebral palsy were detected to understand the effect of selective spinal manipulation on the growth and development of infant rats with cerebral palsy. The results showed that it can promote weight gain, improve balance ability and motor function, promote growth and development of infant cerebral palsy rats, promote growth hormone secretion, and increase the temperature of sensitive parts of the back.

This study illustrates the effect of selective spinal manipulation on the growth and development of infant rats with cerebral palsy, emphasizing the specific procedure and standardized protocol. Body weight measurement, Rotarod test, Foot-fault score, other behavioral tests, and growth hormone detection were performed to evaluate the protocol.

Cerebral palsy (CP) is a refractory pediatric disease with a high prevalence, high disability rate, and difficult treatment. A variety of treatments are ...

<meta charset="utf8"></head><body>为早期产后疼痛研究创建早产大鼠模型

A Preterm Rat Model for Pain Studies

This research delves into the consequences of consistent pinprick stimulation on preterm offspring to ascertain its long-term implications for pain sensitivity. The primary objective of this protocol was to investigate the impact of neonatal pinprick stimuli on the pain threshold in the later stages of life using a preterm rat model. By establishing this model, we aim to advance the research on understanding and managing early postnatal pain associated with prematurity. The findings of this study indicate that while the baseline thresholds to mechanical stimuli remained unaffected, there was a notable increase in mechanical hypersensitivity following complete Freund's adjuvant (CFA) injection in adult rats. Interestingly, compared with male rats, female rats demonstrated heightened inflammatory hypersensitivity. Notably, maternal behavior, the weight of the litters, and the growth trajectory of the offspring remained unchanged by the stimulation. The manifestation of altered nociceptive responses in adulthood after neonatal painful stimuli could be indicative of changes in sensory processing and the functioning of glucocorticoid receptors. However, further research is needed to understand the underlying mechanisms involved and to develop interventions for the consequences of prematurity and neonatal pain in adults.

<meta charset="utf8"></head><body>用于疼痛研究的早产大鼠模型

Here, we present a concise protocol for creating a preterm rat model, facilitating research on early postnatal pain management. The method involves performing a cesarean section three days before the expected birth, extracting preterm rat pups via hysterectomy, and integrating them with the biological offspring of a surrogate dam.

用于疼痛研究的早产大鼠模型

This research delves into the consequences of consistent pinprick stimulation on preterm offspring to ascertain its long-term implications for pain ...