这项工作是支持的CDMRP“，”USUHS资助G188LE，G188MG，G188QC（HL）和USUHS创伤后应激的研究中心。

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没有利益冲突的声明。

创伤后应激障碍的诊断是基于自我报告的精神症状（DSM IV）的潜在主题。没有明确的生物标志物是目前可用于访问潜在的创伤后应激障碍患者的病理生理状态。创伤后应激障碍是一种疾病所引发危及生命的创伤性事件的主要精神症状数月甚至数年后的初始事件幸存者的生活中仍然存在。在创伤后应激障碍的患者最突出的症状持续，显示过度警觉，夸张的惊吓反应延迟14日，15日，16日和丘脑-垂体-肾上腺轴的一个明显的妥协。在人类中，这些症状仍然存在，或出现的延迟三个月，戒烟后的创伤性应激24。我们目前的创伤后应激障碍的生物标志物的研究模型，采用重复为3的连续几天（2小时届40，麻二tailshocks） - 负有不可推卸的尾巴休克模型（ITS）在大鼠体重150克的克制和尾部冲击。这个模型有被模仿在很大程度上的病理生理的创伤后应激障碍17，7，4，10。我们的实验室和其他实验室验证，其模型的应力诱导的大鼠行为和神经生物学的改变，发现PTSD的主题17，7，10，9。具体而言，这些预应力大鼠表现出（1）一个延迟和夸张的惊跳响应出现几天后应激停止，其中给定的压缩时间规模老鼠的生活一个人类相比，对应的二时五十九个月延迟症状PTSD患者（DSM-IV-TR的PTSD Criterian D / E 13），（2）提高血浆皮质酮（CORT），数（10），说明妥协的hypothalamopituitary轴（HPA），和（3）延迟体重增益后应激停止，相应的代谢调节功能障碍，创伤后应激障碍。在文献中没有任何证据，狐臭味，捕食曝光，或害怕增效的惊吓反应，exhi位这些持久性行为和neuroendocrinologic的的表型相关的创伤后应激障碍。 大鼠暴露于一个单一的应力会议（1DS）已经表现出短暂的，而不是持续性异常显示3DS大鼠17的本实验比较了惊吓反应的3DS和1DS大鼠4，7，和应激停止后10天。与以前的工作相一致，应激大鼠表现出升高的基础血浆CORT水平的第一天职位压力17。这些CORT水平CORT水平较高，在3DS大鼠应激暴露的数目比在1DS大鼠敏感。惊吓反应，的1DS大鼠表现出夸张的惊吓后第7天应激反应，，而惊吓过敏变得明显后10天应激在3DS大鼠。因此，外观的惊吓反应过度应激停止后出现到承受应力会话的数目有关。 3DS出现应激动物模型是有用的洞察与创伤后应激障碍的症状和可测量的关键行为的时间停止后的压力与表型相关的生物标志物表达的改​​变。基因组提出申请rMNChip和生物信息学工具识别不同的途径，以及基因和蛋白质生物标志物，这将极大地促进系统生物学研究和理解复杂的，多因素的神经系统疾病，包括创伤后应激障碍的分子机制提供证据的原则。 虽然我们的范式并没有深入的认知和行为方面的更复杂的创伤后应激障碍，我们注意到，改变睡眠模式，在模式1对应的入睡和保持睡眠困难和创伤后应激障碍患者11（DSM-IV-TR创伤后应激障碍的噩梦标准D 13），及逃生/逃避学习，学习的食欲任务中的ITS模型的不足之处<sup12对应于穷人的浓度和记忆障碍，创伤后应激障碍（DSM-IV-TR PTSD标准C 13）。目前的模式具有相关性的创伤后应激障碍的主要症状特点，并提供了一个很好的模式，相关的周边创伤后应激障碍的生物标志物，它可以从病人收集，与中央，机械生物标志物，这不能不6。

biomarkers in an animal model for revealing neural, hematologic, and behavioral correlates of ptsd

鉴定生物标志物的创伤后应激障碍的病理生理的演变（PTSD）是非常重要的，不仅客观的诊断，但也为治疗创伤的疗效和应变能力的评价。正在进行的研究是针对创伤后应激障碍的分子生物标志物，包括创伤后应激诱导蛋白，转录，基因组变异和遗传调制器，使用生物样品从受试者的血液，唾液，尿液，和死后脑组织。不过，这些生物标志物的相关性分子的外设或死亡后的样本，以改变大脑的功能与精神创伤后应激障碍的症状仍然没有得到解决。在这里，我们提出了一种动物模型PTSD外周血及脑中枢的生物标志物，以及行为表型，可以收集和测量，从而提供所需要的相关的中央的创伤后应激障碍的生物标志物，这是机械和pathogno单胞菌，但不能被人收集，与周边的生物标志物和行为表型，它可以。 我们的创伤后应激障碍的动物模型，采用约束和尾部冲击，重复连续三天 - 不可推卸的尾巴休克大鼠模型（ITS）。这个模型模拟的病理生理的创伤后应激障碍17，7，4，10。我们和其他人证实，它的模型诱导行为和神经生物学的改变，类似的发现PTSD的主题17，7，10，9。具体而言，这些预应力大鼠表现出（1）一个延迟和夸张的惊跳响应出现几天后应激停止，其中给定的压缩时间规模老鼠的生活一个人类相比，对应的二时五十九个月延迟症状PTSD患者（DSM-IV-TR的PTSD Criterian D / E 13），（2）提高血浆皮质酮（CORT）好几天了，表示妥协的hypothalamopituitary轴（HPA）和（3）智障博DY体重增加应激停止后，代谢调节功能障碍。 采用这种模式的实验范式是：（1）习得性无助感的范例在测量声惊吓反应（ASR）和图表的身体质量检测大鼠;（2）地区和核显微分离的大鼠脑;（ 3）酶联免疫吸附试验（ELISA）为皮质酮的血药浓度的，（4）的基因表达微阵列加相关的生物信息学工具18。这种芯片，被称为rMNChip，专注于线粒体和线粒体相关的核基因在大鼠专门解决神经元的假设是参与创伤后应激障碍的生物能。

Watch this Scientific Journal Video about Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD at JoVE.com

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

我们描述了一个大鼠模型的创伤后应激障碍（PTSD），揭示了神经内分泌功能的持久性的改变和长期延迟，夸大的恐惧反应，创伤后应激障碍患者的特征。的动物模型，和这里描述的方法，用于相关的生物标志物在脑核，这是机械的，但不能被测量的患者中，与外周血白细胞中的生物标志物，它可以是有用的。

在动物模型揭示神经，血液，创伤后应激障碍和行为相关因素的生物标志物

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for ...

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15.9K 次观看.  Uniformed Services University of the Health Sciences, Bethesda, Maryland. 我们描述了一个大鼠模型的创伤后应激障碍（PTSD），揭示了神经内分泌功能的持久性的改变和长期延迟，夸大的恐惧反应，创伤后应激障碍患者的特征。的动物模型，和这里描述的方法，用于相关的生物标志物在脑核，这是机械的，但不能被测量的患者中，与外周血白细胞中的生物标志物，它可以是有用的。