该NNNS的发展是由美国国立卫生研究院资助的U10 DA 024119-01和U10HD27904和合同N01-HD-2-3159莱斯特博士的支持。文章:儿科卷125，第1号，2010年1月E90-E98。

1，初审观察<ol><li>初始状态观察。考试开始覆盖和睡在睡眠状态1或2个婴儿。 </li><li>记录婴儿的初始状态为静音或主动睡眠，昏昏欲睡，安静觉醒，活动觉醒和哭。 </li></ol> 2，习惯化<ol><li>测量响应减量的一盏灯，拨浪鼓和贝尔反复演示。 </li><li>记录试验的需要，婴儿停止响应每个刺激的数量。 </li></ol> 3折及仰卧<ol><li>拆开包装和脱衣服的婴儿，地点在仰卧位。 </li><li>姿势:记录婴儿的姿势总延长，局部屈曲，屈曲总额，或异常。 </li><li>肤色:记录肤色正常，面色苍白，紫绀或斑点。 </li><li>肤质:记录下列任何一种肤质的迹象都指出:脱落或剥落，excoriations，皮肤松弛或深CREA周围的眼睛和鼻子SES。 </li><li>机芯:记录基线运动活动非常少或无，正常或过量。 </li><li>响应递减到脚的刺激:记录试验次数所花费的婴儿停止响应按脚后跟。 </li></ol> 4，下肢反射<ol><li>将婴儿仰卧按住婴儿的腿部下方的腿放松膝盖。 </li><li>足底抓:反对的婴儿脚球按拇指。 </li><li>记录作为无反应，弱，正常或夸张。 </li><li>巴宾斯基反射:刮开婴儿的脚的侧面。 </li><li>记录作为无反应，弱，正常或夸张。 </li><li>踝阵挛:背屈婴儿的脚几次球。 </li><li>结果如无阵挛，一个，两个或更多，或持续跳动。 </li><li>重复足底抓，巴宾斯基反射和踝阵挛与另一腿。 </li><li>脚性和后坐力:保持双脚婴儿7，腿附近的脚踝，用一只手与脚之间的食指。完全弯曲臀部和膝盖，然后伸出的大腿和小腿和释放。 </li><li>以延伸为无，小，中，强记的速度和数量大腿和小腿的后坐力的记录性。 </li><li>主动腿部动作功率:抓住婴儿的脚动你的食指和中指之间的踝关节以上，并应用温和的阻力。 </li><li>记录活动的运动对抗重力为无，最小，中等或较强。 </li><li>腘窝角:抓住婴儿的足跟底部用手指。在一个流体运动带给婴儿的膝盖到他的肚子，然后伸出腿。重复与婴儿的另一条腿。 </li><li>记录形成在膝盖通过对左，右支腿的上部和下部的腿的角度。 </li></ol> 5，上肢反射和面<ol><li>围巾征:将婴儿的手臂只是胸部Õ以上NE的手。放在婴儿的躯干另一只手，以防止树干的旋转用拇指在婴儿的肘部。轻推肘在胸前，让手臂遇到脖子像一条围巾。重复与婴儿的另一只手臂。 </li><li>记录到其中的肘动作容易之前显著电阻胸部的点。 </li><li>前臂性和后坐力:同时按住婴儿的手臂手腕和完全弯曲手臂的肘部。延伸的前臂和释放一个臂在1秒和另一侧的臂部1秒后。 </li><li>前臂阻力与速度和反冲量的记录数量。 </li><li>主动手臂动作功率:抓住你的食指和中指之间的移动手的手腕和应用温和的抵抗婴幼儿的运动。 </li><li>记录活动的运动对抗重力为无，最小，中等或较强。 </li><li>生根:用一只手握住婴儿的手对他或她的胸部。用另一只手，中风的皮肤在婴儿的嘴角。 </li><li>记录响应，无，转离，弱，完全或夸张的头转投向刺激的一面。 </li><li>握的手:将食指在婴儿的手掌，然后按掌面不接触的手背。重复与婴儿的另一只手。 </li><li>记录响应，无，弱，强或长时间。 </li><li>躯干音:将一只手放在婴儿的臀部并保持婴儿的后脑勺在脖子，另一只手。解除婴幼儿几英寸婴儿床的表面上，使臀部不要接触地面。轻轻将头部向前带婴儿到坐姿弯曲婴儿的躯干。 </li><li>记录干线为无音，有些调，好音或夸张的语气语调。 </li><li>拉坐:握住婴儿的手腕/前臂用你的双手。以T他婴儿的手臂伸展，拉婴儿到一个固定的位置。 </li><li>如婴儿被拉动而坐，观察是否有肌肉抗拉伸的颈部，如果婴儿企图右头到一位置，即在躯干和平行于该主体的中线。 </li></ol> 6，直立回应<ol><li>配售:握住婴儿直立腋下和胸部周围相送。用拇指支撑婴儿的头部运动。提起婴儿，使脚的顶部抚摸，轻轻向下反对在婴儿床或桌面边缘压。重复与另一只脚。 </li><li>注意，如果脚被抬起，然后延伸到"地方"。 </li><li>步:按住婴儿直立腋下和胸部周围相送。用拇指支撑婴儿的头部运动。让脚底摸表面，如步进移动时，婴儿前进。 </li><li>记录ORD响应，没有，一些明显的或夸大的步进。如果踩着未引出，注意，如果婴儿能支持体重，腿部僵硬或双脚跨在剪短的模式。 </li><li>腹悬挂:在婴儿床，通过将手放在婴儿的胸部和腹部悬浮在空气中俯卧婴儿。 </li><li>记录婴儿的头部，四肢和躯干的最终位置。 </li><li>向内弯曲:慢慢挖掘或中风用拇指从椎骨几厘米的侧线，向下从肩部到臀部。重复在另一侧。 </li><li>树干记录响应，因为它弯曲在横向上的刺激侧为无，弱，发育完全，或夸张的凹曲线。 </li></ol> 7，婴儿俯卧<ol><li>爬行:无论是7.1和7.3进行评分从以下动作。随着婴儿俯卧，头部位置在中线和胳膊靠近头部，手心向下。如果婴儿不自发地爬行，刺激轻轻按压手掌上的脚底的反应。 </li><li>记录响应，无，弱，协调或长时间爬行，以及是否刺激应用。 </li><li>抬起头俯卧:从上面的位置，头部无，头转向，短暂提升，持续提升，或如颈部过伸过度反应的纪录提升。 </li></ol> 8，拿起婴儿<ol><li>偎在ARM:握住婴儿在你怀里抱着的地位。不要摇晃或说话的婴儿。方便只拥抱如果存在来自婴儿没有积极参与。 </li><li>偎在肩:保持婴儿在你的肩膀上拥抱位置。 </li><li>记录婴儿的能力，放松或模具，雀巢，和执着以及对相互依偎的任何阻力。 </li></ol> 9，定位/注意事项当你坐在椅子上与婴儿搁在你的大腿上管理方向的项目。有婴儿áTA略微向上倾斜。 <ol><li>无生命的视觉:保持红球约10-12英寸的婴儿的眼睛。轻摇球找到婴儿的焦距范围。然后，慢慢地水平从一个侧面移动球到对方。如果眼睛和头部跟踪到的至少一个侧面，移动球垂直于电弧，以查看是否在婴儿将继续跟踪。 </li><li>无生命的视觉和听觉:轻轻摇动红色拨浪鼓从婴儿的眼睛大约10-12英寸。慢慢地从一侧沿水平方向移动的拨浪鼓到另一个。如果眼睛和头部跟踪到的至少一个侧面，将拨浪鼓垂直于电弧，以查看是否在婴儿将继续跟踪。 </li><li>动画视觉:将你的脸12-18英寸婴儿的面前。从一侧缓缓移动到另一边。如果眼睛和头部跟踪到的至少一个侧面，将面部垂直的圆弧，以查看是否在婴儿将继续跟踪。 </li><li>阿尼姆吃了视觉和听觉:讲了软，稍微高音调的声音，你的脸12-18英寸婴儿的面前。从一侧缓缓移动到另一边。如果眼睛和头部跟踪到的至少一个侧面，将面部垂直的圆弧，以查看是否在婴儿将继续跟踪。 </li><li> 9.1，9.2，9.3和9.4，记录婴儿变成警报的能力，重点关注的对象，请用眼睛和头部水平或垂直，并协调头部和眼球运动。 </li><li>无生命的听觉:不断摇动拨浪鼓，6-12英寸从婴儿的耳朵，淡出人们的视线。重复所以有每边两个试验。 </li><li>动画听觉:柔声细语到的婴儿的耳朵与你的脸了婴儿的视线，约6-12英寸远的。重复所以有每边两个试验。 </li><li>对于9.6和9.7，记录婴儿的能力，成为警报，关闭和/或目光投向刺激。 </li></ol><pCLASS ="jove_title"&gt; 10。婴儿旋<ol><li>的头部和眼睛的进补偏差:握住婴儿直立的臂下面向您用双手交叉于胸前的拇指和周围的婴儿的背部手指。用你的手指来支撑头部的基地。转动你的躯干半圈。旋转向另一个方向。 </li><li>观察婴儿的眼睛/头部运动和有/无眼球震颤。 </li></ol> 11，婴儿仰躺在婴儿床<ol><li>防守动作:随着中线婴儿的头部，按住小布代替了婴儿的眼睛和鼻子，但不阻断鼻孔。 </li><li>婴幼儿的记录活动量，以及武器向布非有向/定向刷卡的存在。 </li><li>不对称的紧张性颈反射（ATNR）:将婴儿的脸慢慢向一侧并与所述夹爪上的肩部的位置简单地持有。等待婴儿落户，并作出姿势adjustment。重复在另一侧。 </li><li>延伸的婴儿的手臂和腿的上表面侧的记录量。 </li><li>莫罗反射:在婴儿床，拿在手中的婴儿仰卧头下一只手，另一只手托住背部和臀部。同时继续支撑头部，迅速降低婴儿。 </li><li>记录婴儿的手臂被绑架和内收。 </li></ol> 12，压力/禁欲<ol><li>考试是肯定的，如果目前在分数的压力/禁欲每个标志。 </li></ol>撮要在整个考试中，观察并记录如下:婴儿的警觉性和反应能力，总基调，电机的成熟，需要安慰性演习，觉醒程度，烦躁，自发的和诱发的活动，震颤量的质量和惊人死不休，皮肤颜色和状态不稳，占主导地位的状态，手到嘴的努力和自我平息努力。 总结成绩在NNNS的分析是基于以前建立的汇总得分1或秤计量习惯，注意，需要处理，运动，自我调节，非最佳反射，反射不对称，觉醒，高渗，低渗，兴奋，嗜睡的质量，应力/禁欲。这些量表的必要心理特性得到了很好的证明，包括跨考官的可靠性，内部一致性，判别，同时施工，同时包括规范健康的足月儿的预测效度1，6，7总结成绩也被合并到配置文件或类型学（下面描述），该分类婴儿成离散的类别。8-10

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约5〜10％的儿童人口有发育障碍，54 NNNS可以在高风险的异常发育结果确定婴儿，是一个重要的临床工具，可让医疗研究人员和医疗人员，以确定这些婴儿并制定干预方案优化这些婴儿的发展，尽早。 该NNNS是一种非侵入性的新生儿评估工具，已被证明是一个大范围的人群，包括风险发育较差预后，治疗，发展性照护品质，在新生儿重症监护病房，表观遗传变化和变异性正常新生儿神经行为的敏感。该考试具有预测效度，不仅医疗成果，如脑性麻痹，神经系统异常，并与大脑疾病的风险，而且还发展成果，如智力和运动功能，行为问题，学校准备和智商的。 </p&gt; 美国小儿科学会呼吁下一个积极的筛查结果转介到早期干预和特殊教育。不需要的诊断对于这样的转介。55 NNNS协议指定与不良预后，可作为预防性干预措施，以减轻或缓解这些赤字目标的行为相关的神经行为缺陷。该NNNS轮廓使我们能够识别，从婴儿谁已经处于危险之中，这是婴儿的风险最高，并且可以提供更好的使用越来越有限资源的大池。

有一种在新生婴儿的神经行为诚信评估长期利益。从科学的角度来看，新生儿神经行为的研究可以告诉后来的行为结果的发育起源的模型。从实际情况来看，早期发现婴幼儿发育较差结局将邀请预防性干预措施，可以改善或减轻长期发展赤字的严重程度的研究。 新生儿重症监护病房的网络神经行为量表（NNNS）1被开发作为高风险的婴儿进行评估，并用于研究和临床实践。这些婴儿谁在风险增加，因为胎儿发育过程中侮辱，如物质暴露或早产或因素，如贫穷，营养不良或缺乏产前护理，可以对宫腔内环境的不利影响和对穷人的发展成果ffect发育中的胎儿。但是，它的配方是基于发展的角度，强调规范性神经行为及其变化，以及风险状况脱轨的影响。因此，NNNS是为了有广泛的适用性。它评估了全系列的婴幼儿神经行为表现，包括神经系统的完整性，行为功能和应力/禁欲的迹象。神经系统组件包括主动和被动的语气，原始反射，并反映婴儿的中枢神经系统和成熟的诚信项目。2，3的新生儿行为评估量表（NBAS）改编的行为组件项目。4应力/禁欲组件的清单&#39;是&#39;或器官系统的基础上芬尼根5和行为迹象的高危婴儿人群如早产儿的观察工作组织&#39;不&#39;的项目。这些神经行为的数据项都被概念框组织的行为状态，因为对他们行为的调节作用，并因为他们自己和他们的动态指标中枢神经系统的完整性（睡眠困扰）。由包括古典反射，语气，姿势，社会和自我监管能力，以及压力和退缩，和国家组织的迹象评估，该NNNS检查是各种行为的敏感高危儿现在和可可用于各种婴儿和用于改变胎龄的婴儿。 考试应在一个开放的婴儿床/ isolette进行对病情稳定的婴儿。这可能是不适合婴幼儿少于28〜32周的胎龄;年龄上限也各不相同，为46周，合理的上限（对于概念性的年龄校正后， 即周胎龄自诞生加上周）。 在NNNS，物品被施用在packagES每个包的焦点或位置的改变开始。施用的顺序是相对不变的。在这里，我们提出了考试之后，在视频显示的协议的内容摘要。在预审观察婴儿睡着了，容易，脱衣服和盖。初始状态是用由Prechtl描述的传统的1-6标准进行评分。2的响应减项（驯化）施用与婴儿在状态1或2，且编码对秤，包括对标准时，婴儿将停止响应（"关闭"）和标准时，该项目被终止了。在不折和仰卧，婴儿的姿势，皮肤颜色和运动，观察和计分尺度，包括在适当情况下，正常，低响应和超响应的标准。皮肤纹理也打进了特定条件的存在。七下肢反射，九上肢反射，四立柱三易RESPonses都给予婴儿的状态3，4或5，其中包括经典的反射，语气和角度的测量，计分尺度也包括在适当情况下，正常，低响应和超响应的标准。婴幼儿，在国家4或5，拾取和拥抱，并分别拿下了偎在手臂和肩膀。这六个方向的项目，然后给予婴儿仍处于状态4或5，对考官的腿上。的处理程序使用，以保持婴儿的方向包时的状态4或5的类型与方向反应得分相处。婴儿被抱起的前庭项目，回到了婴儿床的最后一组反射和观察后考试期间。

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.

研究概况及临床的NNNS的应用 研究 在这里，我们提供了使用在多种婴幼儿人口的NNNS用于研究发表的研究报告的摘要。婴儿出生前暴露于各种各样的物质一直显示在NNNS性能较差。滥用非法和合法药物包括可卡因，11，12阿片类药物，甲基苯丙胺11，13，14大麻，15酒精，11和烟草。16-18这两个烟草产前和产后暴露于二手烟都与贫穷NNNS成绩和种族。 19婴幼儿时的NNNS视觉注意产前可卡因和鸦片剂曝光显示低呼吸性窦性心律不齐20的考试也是更微妙产前暴露，如双酚A，邻苯二甲酸盐和化学品生产合成相关材料的使用敏感ALS在正常人群中21 其他产前暴露研究是治疗的研究。谁需要药物治疗的NAS（新生儿戒断综合征或戒断症状）的婴儿表现出对NNNS比那些没有的NAS更加失调的行为22，对NAS治疗阿片类药物苯巴比妥23婴幼儿有较好的NNNS分数比那些单纯的阿片类药物治疗。24妊娠合并丁丙诺啡与美沙酮海洛因中的NNNS表现在对因治疗婴幼儿的NAS更好成瘾的母亲，23日，怀孕期间母亲24抑郁症常常被与五羟色胺再摄取抑制剂（SRI类），导致在NNNS阴性结果。 25因此，NNNS能够检测不仅强（ 如阿片类药物）药物的效果，但微妙的特效药物为好，鉴别，婴儿谁从这些开发的NAS谁不会，谁的婴儿表现出温和的撤出利科（SRI类）标志，以及在正常的环境中的化学物质的影响。 早产儿的医疗问题导致在考试中受损的神经行为26即使在没有医疗问题，早产儿，足月胎龄已与足月儿相比，在NNNS赤字27在脑成像研究中，早产儿降低局部脑容积显示赤字的NNNS。在NICU（新生儿重症监护室）28更好的发展提高了护理早产儿的NNNS发展的结果，当他们从医院出院。29此外，NNNS早产儿很快发现新生儿重症监护病房出院前有更积极的时候有更多的家庭为中心的护理，发育护理和家长的满意度，减少孕产妇抑郁症和亲职压力，30 NNNS可能在实施护理的发展模式，在新生儿重症监护病房是有用的，并确定荷兰国际集团的婴儿谁可能是高风险的可怜的发育结果，即使没有医疗问题。后者是由NNNS的长期预测效度的支持。 该NNNS的长期预测效度据报道，在一些研究。早产儿，在NNNS性能已经涉及到智力和运动的结果，18个月和31电机状态在24个月和28脑性麻痹的后期开发和受损的运动功能。32在药物暴露的婴儿33运动评分的NNNS预测电机的结果，在18个月。在路径模型，产前物质暴露与差NNNS神经行为这是反过来，3岁和7 34与行为问题 NNNS摘要分数可以被转换成型材，然后可以用于长期预测。每个婴儿被分配到基于互斥配置文件或类别他们的得分在整个汇总分数。 图1A的模式显示，由于在总结成绩表示为标准分数（标准差为单位）的因素，如产前物质暴露与早产儿从1200多个婴儿处于危险之中的一个样本确定了五个文件。在配置文件5 8例呈异常模式。这些婴儿患有需要大量的处理，调节很差很差的注意，他们被高度调动和兴奋的，充满动感的质量差和大量的压力迹象。 如图1B，婴儿曲线5更可能对贝利量表显示2和4年半的异常，对儿童行为量表（CBCL）的行为问题，在入学准备（DIAL-R）和低智商赤字。 NNNS轮廓也被用来预测低风险样品9中发育结果，并与胎盘基因的表观遗传变化。10这些研究提出利用NNNS确定哪些婴儿风险最高的预后较差，发展早期干预措施足以防止或减少后的赤字的严重程度的可能性。 <img alt="图1" fo:content-width="6in" src="/files/ftp_upload/3368/3368fig1highres.jpg" width="600" /> 图1。在其他高危人群的研究中，NNNS已被证明是胎儿宫内生长受限35心脏手术，在谁怀孕，25和未成年母亲的婴儿期间使用可卡因的母亲36产妇抑郁敏感。37 <a href="https://www.jove.com/files/ftp_upload/3368/3368fig1highres.jpg" target="_blank">，请点击这里查看本图的放大版本。</a> 虽然我们已经能够产前因素链接到新生儿神经行为我们不知道的我chanisms负责这些效果。一种可能性是通过外遗传机制，如DNA甲基化是调节基因表达。例如，糖皮质激素受体基因在胎盘由于DNA甲基化降低的活性可以增加胎儿暴露于皮质醇和改变新生儿神经行为。在最近的工作中，NNNS成绩已涉及到表观遗传学改变的几个候选基因在胎盘，10，38-40，以及全基因组的表观遗传效应。41生长受限42和产妇抑郁症在怀孕43期间也与后生改建胎盘的基因，从而影响NNNS分数。这些研究提供了深入了解与新生儿神经行为的分子机制，可以有长远影响的行为发展30，44，45，包括精神健康疾病的发展。46,47 该NNNS也被用于无线个正常的，健康的婴幼儿，研究方法学问题7，48，描述在该人群中的新生儿神经行为的可变性的范围内。6,7这些研究提供了规范的数据与其他群体进行比较。他们也很关键，因为它们表明，正常健康的婴儿是不是一个同质群体;他们的神经行为的组织受多项因素影响的环境中通常不会有风险。在其他规范的样本，考试已用相对于胎行为，49和婴儿气质。50,51因此，虽然NNNS被设计为高风险婴儿也似乎是在低风险人群神经行为变化敏感以及。 临床应用 在临床上，如医院的托儿所，新生儿随访门诊，药物治疗方案和早期干预方案，在NNNS检查可用于帮助婴幼儿的管理和发展护理计划，并告知具体的优势和高风险婴儿脆弱的照顾者。我院（妇女和罗得岛医院的婴儿），并越来越多地在其他医院，考试是标准治疗，在新生儿重症监护病房和一些医院，包括我们的一部分，使用的评估标准照顾婴儿进行新生儿戒断综合征是由于部分在怀孕期间孕妇使用阿片类药物。该NNNS的护理的重要性已通过Sullivan 等 52很好地描述他们指出，新生儿评估已成为需要特别是在新生儿重症监护病房中增加视力和复杂的护理更为关键。有建议的NNNS总结成绩临床解释可用，34以及各种格式的报告临床观察。摘要分数可以计算和百分分数相比较和/或在临床叙述与RECO描述mmendations治疗。初步NNNS意见为开发一种症状为主的护理计划，以帮助婴幼儿的管理和授权照顾者的育儿能力的基准。考试提供了与父母观察婴儿的能力和需求，在制定发展干预计划的专业合作伙伴的绝佳机会。因此，随着NNNS咨询是一个合作的过程，是由婴儿的神经行为功能驱动。由于婴幼儿的医疗和神经行为状态是不断变化的，最好是在重复的NNNS检查，随着时间的推移，或谘询会在定期安排一系列工作要做。因为他们更好地准备把婴儿回家时，他们体会到婴幼儿的长处和弱点靠近放电时间考试可以是特别有帮助的家庭。这有助于他们读婴儿的暗示和信号，支持了他们的信心，养育和发展中的父幼关系有所帮助。此时考试也很有告知出院准备与跟进诊所，社区儿科医生和早期干预计划的建议。53

Watch this Scientific Journal Video about Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale at JoVE.com

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

新生儿重症监护病房的网络神经行为量表（NNNS）的开发作为高风险的婴儿进行评估。这篇文章的目的是描述NNNS，提供的NNNS程序，视频的例子，并讨论其中的考试已使用的方式。

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 ...

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Research

JoVE Journal

Behavior

85.6K 次观看.  Brown University. 新生儿重症监护病房的网络神经行为量表（NNNS）的开发作为高风险的婴儿进行评估。这篇文章的目的是描述NNNS，提供的NNNS程序，视频的例子，并讨论其中的考试已使用的方式。 

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

Stereotactic Injection of MicroRNA-expressing Lentiviruses to the Mouse Hippocampus CA1 Region and Assessment of the Behavioral Outcome

MicroRNAs (miRNAs) are small regulatory single-stranded RNA molecules around 22 nucleotides long that may each target numerous mRNA transcripts and dim an entire gene expression pathway by inducing destruction and/or inhibiting translation of these targets. Several miRNAs play key roles in maintaining neuronal structure and function and in higher-level brain functions, and methods are sought for manipulating their levels for exploring these functions. Here, we present a direct in vivo method for examining the cognitive consequences of enforced miRNAs excess in mice by stereotactic injection of miRNA-encoding virus particles. Specifically, the current protocol involves injection into the hippocampal CA1 region, which contributes to mammalian memory consolidation, learning, and stress responses, and offers a convenient injection site. The coordinates are measured according to the mouse bregma and virus perfusion is digitally controlled and kept very slow. After injection, the surgery wound is sealed and the animals recover. Lentiviruses encoding silencers of the corresponding mRNA targets serve to implicate the specific miRNA/target interaction responsible for the observed effect, with na&iuml;ve mice, mice injected with saline and mice injected with "empty" lentivirus vectors as controls. One month post-injection, the animals are examined in the Morris Water Maze (MWM) for assessing their navigation learning and memory abilities. The MWM is a round tank filled with colored water with a small platform submerged 1 cm below the water surface. Steady visual cues around the tank allow for spatial navigation (sound and the earth's magnetic field may also assist the animals in navigating). Video camera monitoring enables measuring the route of swim and the time to find and amount the platform. The mouse is first taught that mounting the hidden platform offers an escape from the enforced swimming; it is then tested for using this escape and finally, the platform is removed and probe tests examine if the mouse remembers its previous location. Repeated tests over several consecutive days highlight improved performance of tested mice at shorter latencies to find and mount the platform, and as more direct routes to reach the platform or its location. Failure to show such improvement represents impaired learning and memory and/or anxiety, which may then be tested specifically (e.g. in the elevated plus maze). This approach enables validation of specific miRNAs and target transcripts in the studied cognitive and/or stress-related processes.

MicroRNAs have significant roles in brain structure and function. Here we describe a method to enforce hippocampal miRNA over-expression using stereotactic injection of an engineered miRNA-expressing lentivirus. This approach can serve as a relatively rapid way to assess the in vivo effects of over-expressed miRNAs in specific brain regions.

立体定向注射的microRNA表达慢病毒的小鼠海马CA1区和行为结果的评估

MicroRNAs (miRNAs) are small regulatory single-stranded RNA molecules around 22 nucleotides long that may each target numerous mRNA transcripts and dim an ...

科研

行为学

Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic Na&#239;ve Adolescents at High Risk for Psychosis

Growing evidence suggests that movement abnormalities are a core feature of psychosis. One marker of movement abnormality, dyskinesia, is a result of impaired neuromodulation of dopamine in fronto-striatal pathways. The traditional methods for identifying movement abnormalities include observer-based reports and force stability gauges. The drawbacks of these methods are long training times for raters, experimenter bias, large site differences in instrumental apparatus, and suboptimal reliability. Taking these drawbacks into account has guided the development of better&#160;standardized and more efficient procedures to examine movement abnormalities through handwriting analysis software and tablet. Individuals at&#160;risk for psychosis showed significantly more dysfluent pen movements (a proximal measure for dyskinesia) in a handwriting task. Handwriting kinematics offers a great advance over previous methods of assessing dyskinesia, which could clearly be beneficial for understanding the etiology of psychosis.

Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic Na&amp;#239;ve Adolescents at High Risk for Psychosis

Handwriting analysis software significantly improves upon existing instruments measuring movement disorders. Individuals at&#160;risk for psychosis and healthy controls completed handwriting tasks to test for dyskinesia. Results suggest that youth at&#160;risk for psychosis exhibit dyskinesia and that handwriting analysis could significantly contribute to wider dissemination of early identification efforts

笔迹分析显示抗精神病药朴素青少年自发运动障碍的高风险精神病

Growing evidence suggests that movement abnormalities are a core feature of psychosis. One marker of movement abnormality, dyskinesia, is a result of ...

Development of a Virtual Reality Assessment of Everyday Living Skills

Cognitive impairments affect the majority of patients with schizophrenia and these impairments predict poor long term psychosocial outcomes.&#160; Treatment studies aimed at cognitive impairment in patients with schizophrenia not only require demonstration of improvements on cognitive tests, but also evidence that any cognitive changes lead to clinically meaningful improvements.&#160; Measures of &#8220;functional capacity&#8221; index the extent to which individuals have the potential to perform skills required for real world functioning. &#160;Current data do not support the recommendation of any single instrument for measurement of functional capacity.&#160; The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is a novel, interactive gaming based measure of functional capacity that uses a realistic simulated environment to recreate routine activities of daily living. Studies are currently underway to evaluate and establish the VRFCAT&#8217;s sensitivity, reliability, validity, and practicality.&#160;This new measure of functional capacity is practical, relevant, easy to use, and has several features that improve validity and sensitivity of measurement of function in clinical trials of patients with CNS disorders.

A challenge for proving treatment efficacy for cognitive impairments in schizophrenia is finding the optimizing measurement of skills related to everyday functioning.&#160; The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is an interactive gaming based computerized measure aimed at skills associated with everyday functioning, including baseline impairments and treatment related changes.

每天生活技能的虚拟现实评估的发展

Cognitive impairments affect the majority of patients with schizophrenia and these impairments predict poor long term psychosocial outcomes.&#160; ...

Behavioral Assessment of the Aging Mouse Vestibular System

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of studies show changes in balance phenotype with age in rodents, very few isolate the vestibular contribution to balance under either normal conditions or during senescence. We use two standard behavioral tests to characterize the balance performance of mice at defined age points over the lifespan: the rotarod test and the inclined balance beam test. Importantly though, a custom built rotator is also used to stimulate the vestibular system of mice (without inducing overt signs of motion sickness). These two tests have been used to show that changes in vestibular mediated-balance performance are present over the murine lifespan. Preliminary results show that both the rotarod test and the modified balance beam test can be used to identify changes in balance performance during aging as an alternative to more difficult and invasive techniques such as vestibulo-ocular (VOR) measurements.

Motor control and balance performance are known to deteriorate with age. This paper presents a number of standard noninvasive behavioral tests with the addition of a simple rotary stimulus to challenge the vestibular system and show changes in balance performance in a murine model of aging.

衰老小鼠前庭系统的行为评估

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of ...

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

鼠类精神运动警觉测试（rPVT）:一个在大鼠和小鼠的神经行为评估性能的方法

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

Systematic Assessment of Well-Being in Mice for Procedures Using General Anesthesia

In keeping with the 3R Principle (Replacement, Reduction, Refinement) developed by Russel and Burch, scientific research should use alternatives to animal experimentation whenever possible. When there is no alternative to animal experimentation, the total number of laboratory animals used should be the minimum needed to obtain valuable data. Moreover, appropriate refinement measures should be applied to minimize pain, suffering, and distress accompanying the experimental procedure. The categories used to classify the degree of pain, suffering, and distress are non-recovery, mild, moderate, or severe (EU Directive 2010/63). To determine which categories apply in individual cases, it is crucial to use scientifically sound tools.
The well-being-assessment protocol presented here is designed for procedures during which general anesthesia is used. The protocol focuses on home cage activity, the Mouse Grimace Scale, and luxury behaviors such as burrowing and nest building behavior as indicators of well-being. It also uses the free exploratory paradigm for trait anxiety-related behavior. Fecal corticosterone metabolites as indicators of acute stress are measured over the 24-h post-anesthetic period.
The protocol provides scientifically solid information on the well-being of mice following general anesthesia. Due to its simplicity, the protocol can easily be adapted and integrated in a planned study. Although it does not provide a scale to classify distress in categories according to the EU Directive 2010/63, it can help researchers estimate the degree of severity of a procedure using scientifically sound data. It provides a way to improve the assessment of well-being in a scientific, animal-centered manner.

We developed a protocol to assess well-being in mice during procedures using general anesthesia. A series of behavioral parameters indicating levels of well-being as well as glucocorticoid metabolites were analyzed. The protocol can serve as a general aid to estimate the degree of severity in a scientific, animal-centered manner.

全身麻醉下小鼠幸福度的系统评价

In keeping with the 3R Principle (Replacement, Reduction, Refinement) developed by Russel and Burch, scientific research should use alternatives to animal ...

An Instrumented Pull Test to Characterize Postural Responses

Impairment of postural reflexes, termed postural instability, is a common and disabling deficit in Parkinson's disease. To assess postural reflexes, clinicians typically employ the pull test to grade corrective responses to a backward perturbation at the shoulders. However, the pull test is prone to issues with reliability and scaling (score/4). Here, we present an instrumented version of the pull test to more precisely quantify postural responses. Akin to the clinical test, pulls are manually administered except pull force is also recorded. Displacements of the trunk and feet are captured by a semi-portable motion tracking system. Raw data represent distance traveled (in millimeter units), making subsequent interpretation and analysis intuitive. The instrumented pull test also detects variabilities influencing pull test administration, such as pull force, thereby identifying and quantifying potential confounds that can be accounted for by statistical techniques. The instrumented pull test could have application in studies seeking to capture early abnormalities in postural responses, track postural instability over time, and detect responses to therapy.

Impairment of postural reflexes, termed postural instability, is difficult to quantify. Clinical assessments such as the pull test suffer issues with reliability and scaling. Here, we present an instrumented version of the pull test to objectively characterize postural responses.

一种表征姿势反应的仪器拉力测试

Impairment of postural reflexes, termed postural instability, is a common and disabling deficit in Parkinson's disease. To assess postural reflexes, ...

Impact of High-intensity Interval Exercise and Moderate-Intensity Continuous Exercise on the Cardiac Troponin T Level at an Early Stage of Training

An elevation in cardiac troponin T (cTnT), as a highly specific biomarker of cardiomyocyte damage, after moderate-intensity continuous exercise (MCE) has been described. The exercise-induced cTnT response distorts the diagnostic role of the cTnT assay. Although high-intensity interval exercise (HIE) is growing in popularity and concerns remain about its safety, available data related to cTnT release after HIE is limited, which hampers the use of HIE as a health intervention. Here, we present three representative HIE protocols [traditional HIE (repeated 4 min cycling at 90% V&#775;O2max interspersed with 3 min rest, 200 kJ/session); sprint interval exercise (SIE, repeated 1 min cycling at 120% V&#775;O2max interspersed with 1.5 min rest, 200 kJ/session); and repeated sprint exercise (RSE, 40 x 6 s all-out sprints interspersed with 9 s rest)] and one representative MCE protocol (continuous cycling exercise at an intensity of 60% V&#775;O2max, 200 kJ/session). Forty-seven sedentary, overweight young women were randomly assigned to one of four groups (HIE, SIE, RSE, and MCE). Six bouts of respective exercise were performed by every single group, with each being 48 h apart. Meanwhile, for four groups, the duration of the entire testing period was identical, being 10 days. Before and after the first and final exercise bouts, an assessment was conducted of cTnT. The current study provides a frame of reference giving a clear picture of how a specific exercise session affects the circulating cTnT concentration at the early stage of training. The information may assist with clinical interpretations of post-exercise cTnT elevation and guide the prescription of exercise, especially for HIE.

Here, we present protocols of high-intensity interval and moderate-intensity continuous exercise to observe the response of circulating cardiac troponin T (cTnT) concentration to acute exercise over 10 days. The information may assist with clinical interpretations of post-exercise cTnT elevation and guide the prescription of exercise.

高强度间歇锻炼和中强度连续运动对心脏肌钙蛋白T级在训练早期阶段的影响

An elevation in cardiac troponin T (cTnT), as a highly specific biomarker of cardiomyocyte damage, after moderate-intensity continuous exercise (MCE) has ...

Assessment of Midline Lingual Point-Pressure Somatosensation Using Von Frey Hair Monofilaments

Detection and discrimination threshold estimates for oral point pressure are assessed using Von Frey Hair monofilaments. Consistent with previously published protocols, threshold estimates are determined using a two-interval forced choice (2-IFC) paradigm with a three down/one up approach. Detection threshold estimates determine the mean force in which a participant can identify the presence of pressure. During the detection threshold procedure, the participant is instructed to choose which of two sequentially presented observation intervals contained the tactile test stimulus. If the participant performs three correct detections in a row (i.e., 3 &#39;hits&#39;), the researcher decreases the stimulus to the next lower target force level. With one incorrect detection (a &#39;miss&#39;), the researcher increases the force delivered to the next higher level. This threshold estimation approach is known as a 3-down/1-up adaptive staircase. Reponses are recorded on a paper ballot, and a participant&#39;s estimated threshold is defined as the geometric mean of five reversals. During the discrimination threshold procedure, the participant is asked to make a choice between two serially presented stimuli as to which is the &#34;harder&#34; or &#34;stronger&#34; pressure. The same scoring of &#39;hits&#39;, &#39;misses&#39;, and stopping points are used. Detection and discrimination testing for oral point pressure at tongue midline takes approximately 20 min to complete. Using these commercially-available clinical tools, individual touch sensation profiles for the midline tongue can be achieved in a relatively time and cost effective means.

This work describes a standard method to assess tactile sensation at the midline of the tongue tip. Using Von Frey Hair (VFH) monofilaments, this protocol provides estimates of detection and discrimination threshold estimates for oral point pressure (OPP).

使用冯·弗雷头发蒙飞丝的中线语言点-压力感觉的评估

Detection and discrimination threshold estimates for oral point pressure are assessed using Von Frey Hair monofilaments. Consistent with previously ...

Assessment of Memory Function in Pilocarpine-induced Epileptic Mice

Cognitive impairment is one of the most common comorbidities in temporal lobe epilepsy. To recapitulate epilepsy-associated cognitive decline in an animal model of epilepsy, we generated pilocarpine-treated chronic epileptic mice. We present a protocol for three different behavioral tests using these epileptic mice: novel object location (NL), novel object recognition (NO), and pattern separation (PS) tests to evaluate learning and memory for places, objects, and contexts, respectively. We explain how to set the behavioral apparatus and provide experimental procedures for the NL, NO, and PS tests following an open field test that measures the animals&#8217; basal locomotor activities. We also describe the technical advantages of the NL, NO, and PS tests with respect to other behavioral tests for assessing memory function in epileptic mice. Finally, we discuss possible causes and solutions for epileptic mice failing to make 30 s of good contact with the objects during the familiarization sessions, which is a critical step for successful memory tests. Thus, this protocol provides detailed information about how to assess epilepsy-associated memory impairments using mice. The NL, NO, and PS tests are simple, efficient assays that are appropriate for the evaluation of different kinds of memory in epileptic mice.

This article presents experimental procedures for assessing memory impairments in pilocarpine-induced epileptic mice. This protocol can be used to study the pathophysiologic mechanisms of epilepsy-associated cognitive decline, which is one of the most common comorbidities in epilepsy.

皮洛卡平诱导癫痫小鼠记忆功能评估

Cognitive impairment is one of the most common comorbidities in temporal lobe epilepsy. To recapitulate epilepsy-associated cognitive decline in an animal ...