这项工作是由新泽西州委员会对脑损伤的研究。

1。去骨瓣<ol><li>无菌手术部位的准备，包括一个立体的对准仪器鼠标气体麻醉头支架连接麻醉机与 O 2平齐（柏龄科学）（Kopf仪器）小鼠（Kopf仪器），允许在手术过程中持续吸入异氟醚。变暖垫保持在37 ° C下鼠标定位在手术过程中。手术显微镜光源是必要的。实验者应穿白大褂，口罩，脚下覆盖，手套和头罩。所有的工具和材料接触手术部位进行消毒。 </li><li>受伤枢纽，组成了露儿乐女，切断金属年底的20 G 1 ½"针用刀片（Becton Dickinson公司）。轮毂有轻微的偏差应削减和创建环钻（见步骤1.10）可以被用来衡量和编造一个正确的直径损伤枢纽。枢纽之一是每头牲畜的需要。枢纽将连接到颅骨，并连接到大幅面有一个约3毫米的内径开放。设备提供的压力脉冲。 </li><li>固体尼龙线（直径1.7毫米，如杂草修剪线），切成1毫米厚的磁盘使用刀片。同样，动物是需要每一个磁盘。这是用来稳定的环钻，同时进行去骨瓣（见步骤1.10）。 </li><li>老鼠可以被任何压力和年龄（我们主要使用的C57BL / 6年龄1 - 9个月）。鼠标称重，麻醉，在一个小感应室（4-5％，100％O 2的异氟醚预填充）至少1分钟。超前镇痛，buprenorphrine（0.1毫克/公斤）注射腹腔注射，鼠标被放置到一分钟室。镇痛方案应与当地动物使用及护理委员会协商确认。 </li><li>鼠标的头部上方的头发修剪尽可能接近皮肤。鼠标定位在一个立体的对准仪器的安装与设计管理挥发性气体麻醉（Kopf仪器）咬镀。异氟醚气体的水平降低到2％或效果。手术过程中呼吸速率是视觉监测。其他生理参数，如血液气体（P O 2，P的CO 2），可以测量血液的pH值或血压在手术过程中使用适当的设备。 </li><li>人工泪液润滑剂眼膏鼠标使用棉花涂药，以保持干燥的眼睛。碘伏应用于之间的眼睛和颈部70％的酒精棉花撒施皮肤。碘伏和酒精的应用，共3次重复。 </li><li>中线头皮切口是从眼睛到颈部，用手术刀（＃15刀片）和一个小斗牛犬夹的皮肤回缩（精细的科学工具＃18050-28），暴露颅骨，并提供术野清晰。斗牛犬夹子挂头骨的外侧边缘。 </li><li>局部麻醉剂布比卡因（0.025％生理盐水中）是适用于颅骨，用棉撒施和筋膜是从头骨刮牙科工具或骨刮板（例如，精细的科学工具，＃10075-16）的一角。 </li><li>永久性标记是用来标记中间前囟和lambda和颅骨之间的矢状缝和右半球（1〜2毫米，中线右）侧脊。乐泰氰基丙烯酸酯胶（乐泰德白454）下降是在一个塑料重量船和侧面抓钳（精细的科学工具，杜蒙＃6）用于浸到磁盘（见1.3以上的杂草坚实的尼龙绳）胶水，然后按头骨上的标记磁盘。一到两个滴泰加速器交付使用1ml注射器和26 3 / 8 G针引起的胶水硬化的磁盘上。测试光盘的颅骨，然后再继续坚持。 </li><li>放置在磁盘3毫米外径环钻（研究仪器店，宾夕法尼亚大学），并顺时针方向旋转，直到您已通过颅骨切开。经常检查环钻的进展，以避免过远的颅骨和违反硬脑膜的钻井。将会有一个头骨变薄周围的磁盘和颅骨瓣外围会觉得宽松时轻轻按下。将头骨的表面平行/水平牙科工具撬下的头骨和解除骨瓣。从头骨与钳分离骨。如果是有少量出血，不妥协硬脑膜，的，使用棉花撒施施加压力，直到出血停止和防止获取到硬脑膜骨粉。但是，如果有违反硬脑膜症是可见的，应当在动物实验从人道的安乐死淘汰。这一步需要足够的实践实现所需的手术技巧。 </li><li>使用镊子，保持受伤的位置在颅骨骨瓣枢纽，使枢纽偏差的头骨（即长边的枢纽在于头骨的侧脊附近）的曲率一致。同时，用木棍，用刀片切的角度，有锐利尖端，适用于各地的枢纽外边缘的超级胶水凝胶与异性的手，稳定的枢纽，直到它贴在孔直立。必须小心，不要让硬脑膜上的胶水。硬脑膜上的胶会造成的伤害衰减。 </li><li>用一个小纸杯，牙科丙烯酸甲基丙烯酸甲酯（喷气巴特勒施恩​​权限睿麟/维修树脂，丙烯酸酯液体）混合，创造一种粘性的解决方案。使用连接到适用于所有周围的损伤枢纽的水泥无针1毫升注射器。水泥应包括底部2毫米的伤害枢纽以及周围裸露的头骨。头骨的缝合线是用水泥密封，以确保从伤病中的流体丸仍然在颅腔内。 </li><li>填充无菌0.9％氯化钠（生理盐水），使用注射器和迟钝针轮毂。生理盐水将继续在恢复阶段的硬脑膜湿润。此外，如果不留充满伤害枢纽，将显示在集线器连接到头骨的泄漏，并应附加一个新的枢纽。鼠标应给予注射0.25毫升的无菌生理盐水的IP，从立体校准仪器，并放置在没有变暖的铭牌上的电线栏盖的空笼。一些hydragel放在笼底，使小鼠恢复1-2个小时。 </li></ol> 2。诱导损伤<ol><li>打开大幅面设备连接到示波器（泰克TDS 1001B，双通道的Digi存储示波器40兆赫，500Ms.s）和放大器（创伤诱导压力传感器放大器）。确认，大幅面设备（定制设计和制造，弗吉尼亚联邦大学），并连接到它的高压油管（长41cm，体积液2ml，巴克斯特＃2C5643）用无菌水填充，无气泡。在管端的是一个男的鲁尔乐片。露儿的管乐年底关闭，提供释放的钟摆测试脉冲。催芽设备应通过提供约10个测试脉冲。确认摆给平稳信号示波器和放大器。嘈杂的信号，表明在这之前必须删除系统提供的伤害脉冲的空气。脉冲的持续时间应该是20毫秒左右。大幅面设备附带的传感器放大器校准等，为10 mV = 1.0磅每平方英寸（PSI）。一个大气压（atm）= 14.7 PSI。损伤的压力传递通常范围在0.9 - 2.1大气层产生一系列的翻正反射时间和增加肺水肿的死亡率。轻度损伤被认为是一个翻正反射消失时间为2 - 4分和0 - 5％的死亡率。中度损伤被认为是翻正反射消失时间为6 - 10分钟和10 - 20％的死亡率。如果有必要，调整摆的角度来增加或减少脉冲的强度。钟摆的起始位置的角度大约为10度。调整后的大幅面设备，一定要打开露儿的管乐年底。 </li><li>鼠标被放置在4-5％的异氟醚麻醉室（预充电），直至达到手术的麻醉平面。鼠标放在旁边的大幅面设备在一个平台上，并用无菌生理盐水填充的枢纽。大幅面设备的油管与男性露儿乐女性露儿乐装修的枢纽。动物被放置在其一侧，并一次恢复正常的呼吸模式，但之前的动物重新获得完整的意识（1〜2分钟），大幅面设备的钟摆释放造成的伤害的单脉冲。重要的是不会引起伤害，而动物麻醉，因为它可能会导致呼吸衰竭而死亡。应记录脉搏的准确压力。没有受伤，深水动物经过同样的程序与实际流体脉冲诱导损伤的例外。 </li><li>从大幅面设备的动物，应当立即删除，并在它的后面放置监察翻正反射时间。鼠标后已纠正，然后再次简要麻醉水泥和枢纽，从头骨手工。头皮，然后Vetbond组织粘合剂（3M），缝合或钉书针封闭。任何的枢纽硬脑膜或闭塞症是指出。一个闭塞的枢纽，将产生一个未知的幅度衰减损伤。动物被放置在笼子变暖垫，直到日间，然后返回其家笼。 </li></ol> 3。电机的评估，认知和组织学的成果<ol><li>莫TOR LFP造成的赤字可以由使用rotarod测试，一个综合vestibulomotor和感觉功能 21的指标。受伤前所有的动物都必须经过测试，以确定基线阅读和适应环境的老鼠的范式。小鼠是训练上的rotarod设备1小时intertrial的间隔与受伤前两天，每天3次。测量外径36毫米，旋转杆，其中有一个橡胶表面上的延迟，以平衡。速度增加超过180秒的间隔4至40 RPM。每个试用期结束时，动物脱落的rotarod。 </li><li>在不同时间点伤害（通常为1，7至21天）后，小鼠再次对rotarod设备进行测试。受伤后的rotarod测试评价是基于个人得分相对其基线延迟 22 。属于损伤小鼠的平均延迟是深水小鼠相比。 </li><li>认知功能以下大幅面可以测试一个单独设置使用小鼠Morris水迷宫（MWM），创伤后空间学习和工作内存在啮齿类动物中23的敏感指标。小鼠被驯化的范式和测试基线，使用一个可视化平台测试4天前受伤的反应。一个白色的圆形水池（直径1米），是充满了水和无毒的白色油漆。该平台是可见的墙壁上使用标志或标记，并没有视觉线索。 4项试验，鼠标被放置在对面的可视化平台的象限，并找到平台的潜伏期测量。最大试验时间为60秒和鼠标仍然放在15秒的平台上，在每次试验结束。 intertrial间隔是5分钟，在此期间，鼠标加热垫回暖。该平台是移动到一个不同的象限，每个审判和执行四个试验。 </li><li>评估学习，老鼠被训练使用一个隐藏的平台固定在4个象限之一，在不同的时间点，以下损伤（通常为1，7至21天）的MWM。黑与白的线索是放置在墙壁上。整个培训的时间找到平台记录鼠标被放置在其中的象限是伪随机变化。最大试验时间为60秒和鼠标仍然放在平台上为15秒和5分钟之间的试验温暖。小鼠受到8项试验/天，连续3天。要评估的内存保留，动物遭受了60秒探测试验的最后一次训练后的一天。在探测试验，该平台是拆下来确定所花费的时间和象限所在的平台，用于游过的距离。最后，是一个可视化平台测试，以排除可能的电机和开发受伤后的视觉赤字。 </li><li>要确定的LFP损伤的组织学后果，组织intracardial灌注0.9％氯化钠4％多聚甲醛在伤后所需的时间点是固定的。组织后缀一夜之间在4 ° C，然后cryoprotected在10％和30％的蔗糖和嵌入解决方案。冰冻连续切片切低温恒温器和使用各种immuohistochemical和组织学技术进行处理。 </li></ol> 4。代表性的成果: 大幅面设备引起的损伤是可重复的，从动物到动物，特别是足够的手术训练。要保持一致性的伤害，被监控的设备交付硬脑膜压力量。钟摆罢工一个充满水的压克力缸高压油管和鲁尔乐装修，这是连接到贴到动物的去骨瓣网站（图 1A）的伤害枢纽。对于轻度至中度的损伤，摆的角度是产生压力范 ​​围从0.9 - 2.1 ATM和示波器连接到放大器是用于可视化的压力脉冲（图 1B ）。损伤产生一系列的翻正反射时间和增加肺水肿的死亡率。轻度损伤被认为是一个翻正反射消失时间为2 - 4分和0 - 5％的死亡率。中度损伤被认为是翻正反射消失时间为6 - 10分钟和10 - 20％的死亡率。此外，受到大幅面的小鼠可能会​​出现进补的姿态，可扣押的指示。海关检获走私往往与被攻破的硬脑膜。总之，这些研究结果表明，损伤是造成神经损伤。深水动物是连接到大幅面设备，但摆不释放。 为了形象化由大幅面引起的损害，我们已认识到这两者都与损伤反应相关的细胞类型的星形胶质细胞和巨噬细胞的抗体进行免疫细胞化学。胶质纤维酸性蛋白（GFAP）染色揭示整个皮层伤害WH地区增加胶质细胞增生ereas深水小鼠不显示在下面的骨瓣相当于网站（图2A，B）的增加astrocytosis。同样，MAC1染色显示更多的巨噬细胞周围遭受假手术小鼠相比，受伤的部位。此外，还有频繁的物理伤害到皮层组织，在小鼠接受，但不是在深水小鼠（图2C，D）以LFP可见。 可以使用以下温和大幅面的行为测试，以评估双方的认知和运动的成果。 MWM是用来确定对学习和记忆的影响。深水小鼠在试验室中使用的视觉线索，迅速成为更有效的定位每随后在水迷宫训练天的平台。受到轻度LFP的小鼠需要较长时间才能找到隐藏的平台上的第一天的测试相对深水小鼠，但随后出现的学习任务的第三天（图 3A ）。这些结果表明，伤害降低率，小鼠收购的空间学习。为了确定损伤的记忆保持的影响，探测试验后的最后一次训练会议1天。受到轻度LFP表明伤势已经影响小鼠的能力召回平台用于居住（图3B）的位置的老鼠相比，深水小鼠花费更多的时间在目标象限。为了评估运动功能，小鼠对rotarod设备进行测试。受到轻度LFP的小鼠平均延迟时间较短相比下降1，第7和伤后21天（DPI）（图3C）深水小鼠。这些数据表明，损伤小鼠集成vestibulomotor和感觉功能受损。 <img alt="图1" src="/files/ftp_upload/3063/3063fig1.jpg" /> 图1。大幅面设备，并从代表在伤害获得的示波器跟踪。一）的大幅面设备的组成部分:钟摆的立场，并设置固定在预定的角度，以提供所需的力量，充满水与亚克力缸高压油管和一个男性露儿乐接头连接，放大器，和示波器。二）从示波器压力脉冲代表跟踪。峰 - 峰值为2.16伏特，表明1.47大气压的压力。 <img alt="图2" src="/files/ftp_upload/3063/3063fig2.jpg" /> 图2，增强胶质细胞增生和炎症反应，以下大幅面演示的损伤程度。冻结的横截面（20微米）通过大脑受到假手术（A，C）或大幅面损伤（B，D）伤后7天（DPI）鼠标。在震中的开颅皮层图像。 （A，B）组织的抗体，以确定星形胶质细胞染色。胶质纤维酸性蛋白（GFAP）抗体（1:400，Chemicon公司，MAB360）揭示整个皮层LFP损伤（箭头），假手术相比鼠标较高的星形胶质细胞的数量。二抗羊抗鼠594（1:1000）。 （C.四）组织是用一种抗体，以确定巨噬细胞染色。 MAC1抗体（MAC1 -α链CD11b的，BD公司，1:50），揭示更多macrophges和/或激活小胶质细胞损伤周围皮质（箭头）的网站相比，假手术。二抗羊抗鼠CY3（1:50）。比例尺=200μm的C和D，A和B，100微米<img alt="图3" src="/files/ftp_upload/3063/3063fig3.jpg" /> 图3。以下轻度大幅面的行为测试表明，在受伤的深水小鼠相比，赤字。一）受到轻度LFP的小鼠需要更长的时间来学习，比深水小鼠的MWM寻找平台的任务。深水与磷酸锂铁（AVE秒± SEM）1天34.21 ± 3.02比38.64 ± 2.63; 2天24.52 ± 2.84比27.21 ± 2.11; 3天的22.47 ± 2.00比22.08 ± 2.52（1 DPI，N = 9深水时，10 LFP） 。二）受到轻度LFP的小鼠在探测试验24小时花费更少的时间，最后一次训练后的MWM相对深水小鼠（21 DPI，N = 10）在目标象限。三）受到轻度LFP的小鼠关闭rotarod设备秋季早晚高于假小鼠（1，7，和21 DPI，N = 5假，8 LFP）。误差棒代表东南。

<ol>
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没有利益冲突的声明。

LFP方法，这里介绍许多neuropathalogical和行为结果的轻度至中度颅脑损伤，这就是为什么它已成为一个广泛使用的动物模型，脑外伤模型。有几个关键的步骤来考虑，以增加这种技术的有效性和可靠性。举例来说，重要的是，硬脑膜的完整性还没有在去骨瓣损害的唯一的动物受到LFP，并在研究中使用。此外，如果去骨瓣任何胶或水泥闭塞，下方去骨瓣硬脑膜不能承受流体压力的力量，应该被淘汰的动物的研究。最后，如​​果翻正反射消失的时间或死亡率是不预期的范围内，动物不应该被纳入研究。可以增加的压力脉冲的强度，产生更严重的伤害。 正如图1所示，大幅面设备的配置相对简单，损伤程度的可重复性是通过监测在示波器上的大气压力保持。示波器跟踪曲线流畅的造型，表明有流体中的无气泡，可能会干扰感应LFP伤害。测试脉冲应交付前诱导损伤，如果示波器跟踪不会出现一条光滑的曲线，气泡应删除。脉冲持续时间约20毫秒，它代表了诱导时间，在碰撞测试中模拟测量。短脉冲的伤害有可能产生更多的焦距受伤。因此，这种脉冲模式的持续时间人类的脑外伤。 以下大幅面的形态和细胞的变化，包括物理损坏的组织以及如在图2所示的星形胶质细胞和巨噬细胞的数量增加。这是公认的损伤的标志迹象之一是星形胶质细胞增生和胶质瘢痕的形成。胶质瘢痕已被证明有有利和不利影响24。同样，巨噬细胞是已知的过程中积累阶段损伤后，在各种组织的愈合过程开始时25。因此，在相对深水控制LFP样品的数量增加GFAP和MAC1阳性细胞是诱导损伤的指标。那些在深水控制细胞的特异性标志物表达的缺乏表明，单独手术操作没有消极后果，对脑组织的健康和蛋白表达的变化是特定的损伤范式。 在图3所示的温和大幅面的行为后果，包括认知和运动障碍。 MWM的研究结果表明，LFP小鼠最终学习任务，但速度比假老鼠，他们不记得任务以及训练后的一个一天。因此，即使轻度损伤小鼠效率低于善于运用外部线索的过程中，巩固和存储空间信息，必须在随后的测试中检索假小鼠。其他的海马依赖空调的恐惧反应，如认知任务已被证明在 LFP 26小鼠受损。最后，延迟较短的下降rotarod范式LFP小鼠相对深水小鼠在3个星期以下轻度损伤，是一个综合vestibulomotor和感觉功能的赤字指标。较为温和的伤害会透露的认知和运动功能更加显着的变化， 已显示27-30其他群体。 总之，磷酸锂铁是一个有效的模型对人类脑外伤，因为它符合预期的标准。 LFP提供的结构效度，它再现了病因的进程，促使人类脑外伤。具体来说，力和死亡率的幅度是类似发生在轻度和中度的运动和与汽车相关的伤害的警告，在受伤前的外科干预是唯一的动物模型。 LFP也表现在，许多在人类脑外伤观察解剖，生化，神经病理和行为影响的LFP概括面临的有效性。有后LFP局灶性和弥漫的变化检测和影响的不对称性，允许一个比较侧面损伤对侧，患侧的形态学损害。一个需要注意的是，可能只有一个半球受伤更微妙的认知和运动的影响。最后，LFP展品预测的有效性和大幅面技术的可靠性，使诱导损伤20之前或之后的各种药理学和基因操作的评价。如血压，血液的酸碱度，血液的生理参数气体将需要在测试药物，以确定一个治疗剂的作用机制的存在和缺乏衡量。然而，由于TBI的小学和中学的后果的复杂性，这是一项艰巨的任务，以确定一个单一的干预，可以减轻症状。 大幅面技术的未来可考虑使用微流体敲击采用 15流体中的一个微处理器控制，气动仪器，以消除校正钟摆交付部队的需要，并避免业务变量，如气泡。但是，标准的LFP方法许多研究者已经证明是一个可靠和简单的技术，探索潜在的损害和恢复以下脑外伤，这将导致更好的干预和治疗的分子机制。

<ul><li>对小鼠的立体定向对齐仪器（Kopf仪器） </li><li>鼠标气体麻醉头支架（Kopf仪器） </li><li>麻醉机与O 2平齐（柏龄科学） </li><li>麻醉机与O2的flush（柏龄科学） </li><li> Buprenorphrine（韦伯斯特动物供应） </li><li>刷新Lacri润滑油眼膏（费舍尔） </li><li>布比卡因/ Marcaine（韦伯斯特动物供应） </li><li>碘伏溶液（费舍尔） </li><li> 20 G 1 ½"针（碧迪） </li><li>手术刀刀片（＃15）和持有人（碧迪） </li><li>斗牛夹具（精细科学工具） </li><li>牙科工具或骨刮板（精细科学的工具） </li><li>边抓钳杜蒙＃6（精细科学的工具） </li><li> 3mm的外径环钻（宾夕法尼亚大学的研究仪器店） </li><li>固体尼龙线（直径1.7毫米，如杂草修剪线） </li><li>超级胶水凝胶</li><li>乐泰氰基丙烯酸酯胶（乐泰444德白）（汉高公司） </li><li>李连杰丙烯酸酯液体（巴特勒施恩​​） </li><li>烫睿麟/维修树脂（巴特勒施恩​​） </li><li>存储示波器TDS 1001B，40兆赫，500MS / S（泰克） </li><li>创伤诱导压力传感器放大器（定制设计和制造，弗吉尼亚联邦大学） </li><li>大幅面设备（定制设计和制造，弗吉尼亚联邦大学） </li><li>高压油管，长41cm，体积2毫升（巴克斯特） </li><li> 3M Vetbond组织粘合剂（费舍尔） </li></ul>

lateral fluid percussion: model of traumatic brain injury in mice

创伤性脑损伤（TBI）的研究取得了新的动力，由于头部受伤的意识不断提高，导致发病率和死亡率。根据性质上的原发性损伤，脑外伤，复杂和异构的次要后果的结果，这是 1,2再生过程。原发性损伤可诱导大脑直接挫伤，颅骨骨折或由于运动 3,4脑组织造成位移的剪切和拉伸。由此产生的血肿和割伤导致血管反应3,5，和白质的形态和功能的损害，导致弥漫性轴索损伤6-8。附加在大脑中常见的继发性改变，水肿和颅内压增高 9 。继脑外伤有涉及释放兴奋性神经递质，免疫介质和氧自由基10-12，最终导致长期神经系统残疾13,14的生理生化途径的微观改变。因此，选择合适的动物模型，脑外伤，目前类似的细胞和分子事件，在人类和啮齿类动物的脑外伤是学习的内在机制，损伤与修复的关键。 已开发各种脑外伤的实验模型复制在人类身上观察到的脑外伤方面，其中包括三个具体型号，广泛适用于啮齿类动物适应:液压冲击，皮质的影响和体重下降/ 冲击加速度1。液压冲击装置运用到完整的硬脑膜一个短暂的流体压力脉冲通过骨瓣产生伤害。脉冲是一个惊人的水库流体活塞摆。敲击产生短暂的位移和变形的神经组织 1,15 。相反，皮质撞击伤可通过机械能完整的硬脑膜下气压 16,17刚性撞击。体重下降/碰撞模型的特点是由一个一个具体的大规模封闭颅骨18杆的秋天。其中脑外伤模型，磷酸锂铁是最常用的模型来评价混合局灶性和弥漫性脑损伤 19 。它是可重复的和标准化，让损伤参数的操纵。 LFP概括受伤观察在人类身上，从而使临床相关，允许探索新型疗法用于临床的翻译20。 我们描述了详细的协议来执行小鼠LFP程序。造成的伤害是轻度至中度，如大脑皮质，海马和胼胝体最脆弱的地区，的。海马和电机的学习任务是探索以下LFP。

Watch this Scientific Journal Video about Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice at JoVE.com

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

横向流体冲击（LFP），一个建立在小鼠的脑外伤模型，是证明。 LFP满足动物模型的三个主要标准:有效性，可靠性和临床相关性。轮毂固定的程序，包括外科开颅手术，其次是诱导损伤，造成局灶性和弥漫性损伤，是描述。

侧向液压冲击:创伤性脑损伤小鼠模型

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and ...

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40.4K 次观看.  University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School. 横向流体冲击（LFP），一个建立在小鼠的脑外伤模型，是证明。 LFP满足动物模型的三个主要标准:有效性，可靠性和临床相关性。轮毂固定的程序，包括外科开颅手术，其次是诱导损伤，造成局灶性和弥漫性损伤，是描述。

视频: Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

A Method to Inflict Closed Head Traumatic Brain Injury in Drosophila

Traumatic brain injury (TBI) affects millions of people each year, causing impairment of physical, cognitive, and behavioral functions and death. Studies using Drosophila have contributed important breakthroughs in understanding neurological processes. Thus, with the goal of understanding the cellular and molecular basis of TBI pathologies in humans, we developed the High Impact Trauma (HIT) device to inflict closed head TBI in flies. Flies subjected to the HIT device display phenotypes consistent with human TBI such as temporary incapacitation and progressive neurodegeneration. The HIT device uses a spring-based mechanism to propel flies against the wall of a vial, causing mechanical damage to the fly brain. The device is inexpensive and easy to construct, its operation is simple and rapid, and it produces reproducible results. Consequently, the HIT device can be combined with existing experimental tools and techniques for flies to address fundamental questions about TBI that can lead to the development of diagnostics and treatments for TBI. In particular, the HIT device can be used to perform large-scale genetic screens to understand the genetic basis of TBI pathologies.

A Method to Inflict Closed Head Traumatic Brain Injury in Drosophila

Here we describe a method to inflict closed head traumatic brain injury (TBI) in Drosophila. This method provides a gateway to investigate the cellular and molecular mechanisms that underlie TBI pathologies using the vast array of experimental tools and techniques available for flies.

方法对敌人造成闭合性颅脑创伤性脑损伤<em&gt;果蝇</em

Traumatic brain injury (TBI) affects millions of people each year, causing impairment of physical, cognitive, and behavioral functions and death. Studies ...

科研

神经科学

Imaging Neural Activity in the Primary Somatosensory Cortex Using Thy1-GCaMP6s Transgenic Mice

The mammalian brain exhibits marked symmetry across the sagittal plane. However, detailed description of neural dynamics in symmetric brain regions in adult mammalian animals remains elusive. In this study, we describe an experimental procedure for measuring calcium dynamics through dual optical windows above bilateral primary somatosensory corticies (S1) in Thy1-GCaMP6s transgenic mice using 2-photon (2P) microscopy. This method enables recordings and quantifications of neural activity in bilateral mouse brain regions one at a time in the same experiment for a prolonged period in vivo. Key aspects of this method, which can be completed within an hour, include minimally invasive surgery procedures for creating dual optical windows, and the use of 2P imaging. Although we only demonstrate the technique in the S1 area, the method can be applied to other regions of the living brain facilitating the elucidation of structural and functional complexities of brain neural networks.

Imaging Neural Activity in the Primary Somatosensory Cortex Using Thy1-GCaMP6s Transgenic Mice

We describe an experimental procedure for measuring neuronal activity through dual optical windows above bilateral primary somatosensory corticies (S1) in Thy1-GCaMP6s transgenic mice using 2-photon (2P) microscopy in vivo.

胸腺1-gmcmp6 转基因小鼠在原代体血源皮质中的成像神经活性

The mammalian brain exhibits marked symmetry across the sagittal plane. However, detailed description of neural dynamics in symmetric brain regions in ...

Automated Gait Analysis in Mice with Chronic Constriction Injury

The von Frey test is a classical method that has been widely used to examine the sensory function of neuropathic pain animals. However, it has some disadvantages such as subjective data and the requirement of a skilled, experienced experimenter. To date, a variety of modifications have improved the von Frey method, but it still has a few limitations. Recent reports have suggested that gait analysis produces more accurate and objective data from the neuropathic animals. This protocol demonstrates how to perform the automated gait analysis to determine the degree of neuropathic pain in mice. After several days of acclimation, the mice were allowed to walk freely on the glass floor to illuminate footprints. Then, quantification of the footprints and gait were performed through video clips with automatic analysis of various walking parameters, such as area of paw print, swing time, angle of paw, etc.
The main purpose of this study is to describe the methodology of automated gait analysis and briefly compare it with data from the classical sensory test using von Frey filament.

The precise assessment of pain response in a neuropathic animal model is critical to investigate the pathophysiology of pain diseases and develop new analgesics. We present a sensitive and objective method to determine the sensory function of the rodent hind paw by an automated gait analysis system.

慢性压迫性损伤小鼠步态的自动分析

The von Frey test is a classical method that has been widely used to examine the sensory function of neuropathic pain animals. However, it has some ...

A Novel In Vitro Model of Blast Traumatic Brain Injury

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the detonation of explosive devices, however, the mechanisms that underlie the brain damage resulting from blast overpressure exposure are not entirely understood and are believed to be unique to this type of brain injury. Preclinical models are crucial tools that contribute to better understand blast-induced brain injury. A novel in vitro blast TBI model was developed using an open-ended shock tube to simulate real-life open-field blast waves modelled by the Friedlander waveform. C57BL/6N mouse organotypic hippocampal slice cultures were exposed to single shock waves and the development of injury was characterized up to 72 h using propidium iodide, a well-established fluorescent marker of cell damage that only penetrates cells with compromised cellular membranes. Propidium iodide fluorescence was significantly higher in the slices exposed to a blast wave when compared with sham slices throughout the duration of the protocol. The brain tissue injury is very reproducible and proportional to the peak overpressure of the shock wave applied.

A Novel In Vitro Model of Blast Traumatic Brain Injury

This paper describes a novel model of primary blast traumatic brain injury. A compressed-air driven shock tube is used to expose in vitro mouse hippocampal slice cultures to a single shock wave. This is a simple and rapid protocol generating a reproducible brain tissue injury with a high throughput.

一种新的脑外伤体损伤模型

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the ...

Effects of Blast-induced Neurotrauma on Pressurized Rodent Middle Cerebral Arteries

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral vascular effects. Impact (i.e., non-blast) traumatic brain injury (TBI) is known to decrease pressure autoregulation in the cerebral vasculature in both humans and experimental animals. The hypothesis that blast-induced traumatic brain injury (bTBI), like impact TBI, results in impaired cerebral vascular reactivity was tested by measuring myogenic dilatory responses to reduced intravascular pressure in rodent middle cerebral arterial (MCA) segments from rats subjected to mild bTBI using an Advanced Blast Simulator (ABS) shock tube. Adult, male Sprague-Dawley rats were anesthetized, intubated, ventilated and prepared for Sham bTBI (identical manipulation and anesthesia except for blast injury) or mild bTBI. Rats were randomly assigned to receive Sham bTBI or mild bTBI followed by sacrifice 30 or 60 min post-injury. Immediately after bTBI, righting reflex (RR) suppression times were assessed, euthanasia at the time points post-injury was completed, the brain was harvested and the individual MCA segments were collected, mounted and pressurized. As the intraluminal pressure perfused through the arterial segments was reduced in 20 mmHg increments from 100 to 20 mmHg, MCA diameters were measured and recorded. With decreasing intraluminal pressure, MCA diameters steadily increased significantly above baseline in the Sham bTBI groups while MCA dilator responses were significantly reduced (p &#60; 0.05) in both bTBI groups as evidenced by the impaired, smaller MCA diameters recorded for the bTBI groups. In addition, RR suppression in the bTBI groups was significantly (p &#60; 0.05) higher than in the Sham bTBI groups. MCA&#39;s collected from the Sham bTBI groups exhibited typical vasodilatory properties to decreases in intraluminal pressure while MCA&#39;s collected following bTBI exhibited significantly impaired myogenic vasodilatory responses to reduced pressure that persisted for at least 60 min after bTBI.

Here, we present a protocol to describe methods for ex vivo vascular reactivity determination following a primary blast traumatic brain injury (bTBI) using isolated, pressurized, rodent middle cerebral arterial (MCA) segments. bTBI induction is accomplished using a shock tube, also known as an Advanced Blast Simulator (ABS) device.

爆炸性神经损伤对压生啮鼠中脑动脉的影响

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral ...

Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also demonstrate that traumatic brain injuries cause changes to the gut microbiota. However, mechanisms underlying the bidirectional regulation of the brain-gut axis remain unknown. Currently, few models exist for studying the changes in gut microbiota after traumatic brain injury. Therefore, the presented study combines protocols for inducing traumatic brain injury using a lateral fluid percussion device and analysis of caecum samples following injury for investigating alterations in the gut microbiome. Alterations of the gut microbiota composition after traumatic brain injury are determined using 16S-rDNA sequencing. This protocol provides an effective method for studying the relationships between enteric microorganisms and traumatic brain injury.

Presented here is a protocol to induce diffuse traumatic brain injury using a lateral fluid percussion device followed by the collection of the caecum content for gut microbiome analysis.

研究小鼠创伤性脑损伤后凯库姆微生物群的改动

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also ...

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous variability and heterogeneity (age, gender, type of trauma, other possible pathologies, etc.), animal models play a key role in unraveling factors that are limitations in clinical research. They provide a standardized and controlled setting to investigate the biological mechanisms of injury and repair following TBI. However, not all animal models mimic the diffuse and subtle nature of mTBI effectively. For example, the commonly used controlled cortical impact (CCI) and lateral fluid percussion injury (LFPI) models make use of a craniotomy to expose the brain and induce widespread focal trauma, which are not commonly seen in mTBI. Therefore, these experimental models are not valid to mimic mTBI. Thus, an appropriate model should be used to investigate mTBI. The Marmarou weight drop model for rats induces similar microstructural alterations and cognitive impairments as seen in patients who sustain mild trauma; therefore, this model was selected for this protocol. Conventional computed tomography and magnetic resonance imaging (MRI) scans commonly show no damage following a mild injury, because mTBI induces often only subtle and diffuse injuries. With diffusion weighted MRI, it is possible to investigate microstructural properties of brain tissue, which can provide more insight into the microscopic alterations following mild trauma. Therefore, the goal of this study is to obtain quantitative information of a selected region-of-interest (i.e., hippocampus) to follow up disease progression after obtaining a mild and diffuse brain injury.

The overall goal of this procedure is to obtain quantitative microstructural information of the hippocampus in a rat with mild traumatic brain injury. This is done using an advanced diffusion-weighted magnetic resonance imaging protocol and region-of-interest based analysis of parametric diffusion maps.

轻度创伤性脑损伤大鼠海马学的高级扩散成像

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous ...

Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the United States. In fact, TBI is a contributing factor to over a third of all injury-related mortality. Nonetheless, the cellular and molecular mechanisms underlying the pathophysiology of TBI are poorly understood. Thus, preclinical models of TBI capable of replicating the injury mechanisms pertinent to TBI in human patients are a critical research need. The controlled cortical impact (CCI) model of TBI utilizes a mechanical device to directly impact the exposed cortex. While no model can full recapitulate the disparate injury patterns and heterogeneous nature of TBI in human patients, CCI is capable of inducing a wide range of clinically applicable TBI. Furthermore, CCI is easily standardized allowing investigators to compare results across experiments as well as across investigative groups. The following protocol is a detailed description of applying a severe CCI with a commercially available impacting device in a murine model of TBI.

Here we describe a protocol for the induction of murine traumatic brain injury via an open-head controlled cortical impact.

创伤性脑损伤诱导受控皮质冲击的母模型

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the ...

Low-intensity Blast Wave Model for Preclinical Assessment of Closed-head Mild Traumatic Brain Injury in Rodents

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of medical visits in the United States. There are currently no FDA-approved treatments available for TBI. The increased incidence of military-related, blast-induced TBI further accentuates the urgent need for effective TBI treatments. Therefore, new preclinical TBI animal models that recapitulate aspects of human blast-related TBI will greatly advance the research efforts into the neurobiological and pathophysiological processes underlying mild to moderate TBI as well as the development of novel therapeutic strategies for TBI.
Here we present a reliable, reproducible model for the investigation of the molecular, cellular, and behavioral effects of mild to moderate blast-induced TBI. We describe a step-by-step protocol for closed-head, blast-induced mild TBI in rodents using a bench-top setup consisting of a gas-driven shock tube equipped with piezoelectric pressure sensors to ensure consistent test conditions. The benefits of the setup that we have established are its relative low-cost, ease of installation, ease of use and high-throughput capacity. Further advantages of this non-invasive TBI model include the scalability of the blast peak overpressure and the generation of controlled reproducible outcomes. The reproducibility and relevance of this TBI model has been evaluated in a number of downstream applications, including neurobiological, neuropathological, neurophysiological and behavioral analyses, supporting the use of this model for the characterization of processes underlying the etiology of mild to moderate TBI.

We present here a protocol of a blast wave model for rodents to investigate neurobiological and pathophysiological effects of mild to moderate traumatic brain injury. We established a gas-driven, bench-top setup equipped with pressure sensors allowing for reliable and reproducible generation of blast-induced mild to moderate traumatic brain injury.

低强度冲击波模型用于啮齿动物闭头轻度创伤性脑损伤的临床前评估

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of ...

Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and understanding the mechanisms of how a TBI alters brain function. The availability of multiple animal models of TBI is necessary to model the different aspects and severities of TBI seen in people. This manuscript describes the use of a midline closed head injury (CHI) to develop a mouse model of mild TBI. The model is considered mild because it does not produce structural brain lesions based on neuroimaging or gross neuronal loss. However, a single impact creates enough pathology that cognitive impairment is measurable at least 1 month after injury. A step-by-step protocol to induce a CHI in mice using a stereotaxically guided electromagnetic impactor is defined in the paper. The benefits of the mild midline CHI model include the reproducibility of the injury-induced changes with low mortality. The model has been temporally characterized up to 1 year after the injury for neuroimaging, neurochemical, neuropathological, and behavioral changes. The model is complementary to open skull models of controlled cortical impact using the same impactor device. Thus, labs can model both mild diffuse TBI and focal moderate-to-severe TBI with the same impactor.

The protocol describes mild traumatic brain injury in a mouse model. In particular, a step-by-step protocol to induce a mild midline closed head injury and the characterization of the animal model is fully explained.

小鼠轻度创伤性脑损伤的电磁控制闭头模型

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and ...