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。

<ol>
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X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rat+Mitochondrion-Neuron+Focused+Microarray+(rMNChip)+and+Bioinformatics+Tools+for+Rapid+Identification+of+Differential+Pathways+in+Brain+Tissues.">Rat Mitochondrion-Neuron Focused Microarray (rMNChip) and Bioinformatics Tools for Rapid Identification of Differential Pathways in Brain Tissues.</a> Int. J. Biol. Sci. 7, 308-322 (2011).</li><li>Su, D. M., Zhang, Q., Wang, X., He, P., Zhu, Y. J., Zhao, J., Rennert, O. M., Su, Y. 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A., Yang, J., Tao, L., Nguyen, H., He, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Undetectable+and+Decreased+Expression+of+KIAA1949+(Phostensin)+Encoded+on+Chromosome+6p21.33+in+Human+Breast+Cancers+Revealed+by+Transcriptome+Analysis.">Undetectable and Decreased Expression of KIAA1949 (Phostensin) Encoded on Chromosome 6p21.33 in Human Breast Cancers Revealed by Transcriptome Analysis.</a> J. Cancer. 1, 38-50 (2010).</li><li>Yehuda, R., Yang, R. K., Buchsbaum, M. S., Golier, J. 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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 ...

biomarkers-an-animal-model-for-revealing-neural-hematologic

Research

JoVE Journal

Medicine

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。

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

Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. It has been routinely simulated in animals by several techniques, including infusion of exogenous bacterial toxin (endotoxemia) or bacteria (bacteremia), as well as surgical perforation of the cecum by cecal ligation and puncture (CLP)1-3. CLP allows bacteria spillage and fecal contamination of the peritoneal cavity, mimicking the human clinical disease of perforated appendicitis or diverticulitis. The severity of sepsis, as reflected by the eventual mortality rates, can be controlled surgically by varying the size of the needle used for cecal puncture2. In animals, CLP induces similar, biphasic hemodynamic cardiovascular, metabolic, and immunological responses as observed during the clinical course of human sepsis3. Thus, the CLP model is considered as one of the most clinically relevant models for experimental sepsis1-3.
Various animal models have been used to elucidate the intricate mechanisms underlying the pathogenesis of experimental sepsis. The lethal consequence of sepsis is attributable partly to an excessive accumulation of early cytokines (such as TNF, IL-1 and IFN-&gamma;)4-6 and late proinflammatory mediators (e.g., HMGB1)7. Compared with early proinflammatory cytokines, late-acting mediators have a wider therapeutic window for clinical applications. For instance, delayed administration of HMGB1-neutralizing antibodies beginning 24 hours after CLP, still rescued mice from lethality8,9, establishing HMGB1 as a late mediator of lethal sepsis. The discovery of HMGB1 as a late-acting mediator has initiated a new field of investigation for the development of sepsis therapies using Traditional Chinese Herbal Medicine. In this paper, we describe a procedure of CLP-induced sepsis, and its usage in screening herbal medicine for HMGB1-targeting therapies.

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection, and can be simulated by a surgical technique termed cecal ligation and puncture (CLP). Here we describe a method to use CLP-induced animal model to screen medicinal herbs for therapeutic agents.

脓毒症动物模型，用于评估新型草药疗法

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. It has been routinely simulated in animals by several ...

科研

医学

An Isolated Working Heart System for Large Animal Models

Since its introduction in the late 19th century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart model, have been invaluable tools for studying cardiovascular function and disease1-15. Although the Langendorff heart preparation can be used for any mammalian heart, most studies involving this apparatus use small animal models (e.g., mouse, rat, and rabbit) due to the increased complexity of systems for larger mammals1,3,11. One major difficulty is ensuring a constant coronary perfusion pressure over a range of different heart sizes &#8211; a key component of any experiment utilizing this device1,11. By replacing the classic hydrostatic afterload column with a centrifugal pump, the Langendorff working heart apparatus described below allows for easy adjustment and tight regulation of perfusion pressures, meaning the same set-up can be used for various species or heart sizes. Furthermore, this configuration can also seamlessly switch between constant pressure or constant flow during reperfusion, depending on the user&#8217;s preferences. The open nature of this setup, despite making temperature regulation more difficult than other designs, allows for easy collection of effluent and ventricular pressure-volume data.

Most studies involving the Langendorff apparatus use small animal models due to the increased complexity of systems for larger mammals. We describe a Langendorff system for large animal models that allows for use across a range of species, including humans, and relatively easy data acquisition.

一个孤立的工作心脏系统的大型动物模型

Since its introduction in the late 19th century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart ...

Bioluminescence Imaging of an Immunocompetent Animal Model for Glioblastoma

In contrast to commonly reported human glioma xenograft animal models, GL261 murine glioma xenografts recapitulate nearly all relevant clinical and histopathologic features of the human disease. When GL261 cells are implanted intracranially in syngeneic C57BL/6 mice, the model has the added advantage of maintaining an intact immune microenvironment. Stable expression of luciferase in GL261 cells allows non-invasive cost effective bioluminescence monitoring of intracranial tumor growth. We have recently demonstrated that luciferase expression in GL261 cells does not affect the tumor growth properties, tumor cell immunomodulatory cytokine expression, infiltration of immune cells into the tumor, or overall survival of animals bearing the intracranial tumor. Therefore, it appears that the GL261 luciferase glioma model can be useful in the study of novel chemotherapeutic and immunotherapeutic modalities. Here we report the technique for generating stable luciferase expression in GL261 cells and how to study the in vitro and in vivo growth of the tumor cells by bioluminescence imaging.

GL261 glioma cells provide a useful immunocompetent animal model of glioblastoma. The goals of this protocol are to demonstrate proper techniques for monitoring intracranial tumor growth using in vivo bioluminescence imaging, and to verify the utility of luciferase-modified GL261 cells for studying tumor immunology and immunotherapeutic approaches for treating glioblastoma.

免疫活性动物模型胶质母细胞瘤的生物发光成像

In contrast to commonly reported human glioma xenograft animal models, GL261 murine glioma xenografts recapitulate nearly all relevant clinical and ...

A Repetitive Concussive Head Injury Model in Mice

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of knowledge on the injury and its effects. To develop a better understanding of concussions, animals are often used because they provide a controlled, rigorous, and efficient model. Studies have adapted traditional animal models to perform mTBI to stimulate mild injury severity by changing the injury parameters. These models have been used because they can produce morphologically similar brain injuries to the clinical condition and provide a spectrum of injury severities. However, they are limited in their ability to present the identical features of injuries in patients. Using a traditional impact system, a repetitive concussive injury (rCHI) model can induce mild to moderate human-like concussion. The injury degree can be determined by measuring the period of loss of consciousness (LOC) with a sign of a transient termination of breathing. The rCHI model is beneficial to use for its accuracy and simplicity in determining mTBI effects and potential treatments.

Concussion presents the most common type of traumatic brain injury. Therefore, a repetitive concussive animal model, which replicates the important features of an injury in patients, may provide a means to study concussion in a rigorous, controlled, and efficient manner.

重复震荡颅脑损伤模型小鼠

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of ...

An Anesthesia, Surgery, and Harvest Method for the Evaluation of Transpedicular Screws Using an In Vivo Porcine Lumbar Spine Model

Pedicle screw fixation is the gold standard for the treatment of spinal diseases. However, many studies have reported the issue of loosening pedicle screws after spinal surgery, which is a serious concern. To address this problem, diverse types of pedicle screws have been examined to identify those with good fixation strength and osseointegration in spine bone. The porcine spine is a good alternative for the human spine in the evaluation of pedicle screws due to the anatomical size, mechanical characteristics, and cost. Although several studies have reported that pedicle screws are efficient in the porcine model, no study has described detailed protocols for the evaluation of a pedicle screw using the porcine model. Here, we describe a detailed method for evaluating transpedicular screws using an in vivo porcine lumbar spine model. The technical details for anesthesia, spine surgery, and harvest provided here will facilitate with the evaluation of the transpedicular screw fixation model.

An Anesthesia, Surgery, and Harvest Method for the Evaluation of Transpedicular Screws Using an In Vivo Porcine Lumbar Spine Model

Here, we introduce a method to evaluate transpedicular screws by using an in vivo porcine lumbar spine model.

用于评估椎弓根螺钉的麻醉，手术和收获方法<em&gt;体内</em&gt;猪腰椎模型

Pedicle screw fixation is the gold standard for the treatment of spinal diseases. However, many studies have reported the issue of loosening pedicle ...

A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but regardless of the approach, an in vivo model is needed to test each treatment. The pig is one of the most used large animal models for cardiovascular disease. Its heart is very similar in anatomy and function to that of a human. The ameroid placement technique creates an ischemic area of the heart, which has many useful applications in studying myocardial infarction. This model has been used for surgical research, pharmaceutical studies, imaging techniques, and cell therapies.
There are several ways of inducing an ischemic area in the heart. Each has its advantages and disadvantages, but the placement of an ameroid constrictor remains the most widely used technique. The main advantages to using the ameroid are its prevalence in existing research, its availability in various sizes to accommodate the anatomy and size of the vessel to be constricted, the surgery is a relatively simple procedure, and the post-operative monitoring is minimal, since there are no external devices to maintain. This paper provides a detailed overview of the proper technique for the placement of the ameroid constrictor.

The purpose of this protocol is to demonstrate the placement of a delayed constricting device (an ameroid constrictor) around a coronary artery in a swine model. This device creates an ischemic area of the heart that is useful for studying new diagnostic imaging techniques and new methods of treatment.

应用 Ameroid 的猪慢性心肌缺血模型

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but ...

Assessment of Plasma Coagulation on Liver Tissue in a Large Animal Model In Vivo

Plasma coagulation as a form of electrocautery is used in liver surgery for decades to seal the large liver cut surface after major hepatectomy to prevent hemorrhages at a later stage. The exact effects of plasma coagulation on liver tissue are only poorly examined. In our porcine model, the coagulation effects can be examined close to the clinical application. A combined laser Doppler flowmeter and spectrophotometer documents microcirculation changes during coagulation at 8 mm tissue depth noninvasively, providing quantifiable information about hemostasis beyond the subjective clinical impression. The temperature at coagulation site is assessed with an infrared thermometer prior and post coagulation and with a thermographic camera during coagulation, a measurement of the gas beam temperature is not possible due to the upper threshold of the devices. The depth of coagulation is measured microscopically on hematoxylin/eosin stained sections after calibration with an object micrometer and gives an exact information about the power setting-coagulation depth-relation. The sealing effect is examined on the bile ducts as it is not possible for a plasma coagulator to seal larger blood vessels. Burst pressure experiments are carried out on explanted organs to rule out blood pressure related effects.

Assessment of Plasma Coagulation on Liver Tissue in a Large Animal Model In Vivo

Here we present a protocol to experimentally assess plasma coagulation in liver tissue in vivo. In a porcine model, microcirculation is examined by laser Doppler, coagulation depth is measured histologically, temperature at coagulation site by infrared thermometer and thermographic camera, and duct sealing effect is documented by burst pressure experiments.

大动物模型肝组织血浆凝固的评价

Plasma coagulation as a form of electrocautery is used in liver surgery for decades to seal the large liver cut surface after major hepatectomy to prevent ...

Intra-Operative Neural Monitoring of Thyroid Surgery in a Porcine Model

Intraoperative injury to the recurrent laryngeal nerve (RLN) can cause vocal cord paralysis, which interferes with speech and can potentially interfere with breathing. In recent years, intraoperative neural monitoring (IONM) has been widely adapted as an adjunct technique to localize the RLN, detect RLN injury, and predict vocal cord function during the operations. Many studies have also used animal models to investigate new applications of IONM technology and to develop reliable strategies for preventing intraoperative RLN injury. The aim of this article is to introduce a standard protocol for using a porcine model in IONM research. The article demonstrates the procedures for inducing general anesthesia, performing tracheal intubation, and experimental design to investigate the electrophysiological characteristics of RLN injuries. Applications of this protocol can improve overall efficacy in implementing the 3R principle (replacement, reduction and refinement) in porcine IONM studies.

This study aims to develop a standard protocol of intra-operative neural monitoring of thyroid surgery in a porcine model. Here, we present a protocol to demonstrate general anesthesia, to compare different types of electrodes, and to investigate the electrophysiological characteristics of the normal and injured recurrent laryngeal nerves.

猪手术模型对甲状腺手术的手术内神经监测

Intraoperative injury to the recurrent laryngeal nerve (RLN) can cause vocal cord paralysis, which interferes with speech and can potentially interfere ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

用线 Myography 测定小鼠肠系膜动脉的等轴收缩力

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

Manufacture of a Multi-Purpose Low-Cost Animal Bench-Model for Teaching Tracheostomy

Tracheostomy is one of the most frequent procedures, performed through various techniques in the intensive care unit and emergency situations. Despite this, there is a lack of training on this procedure that affects its outcome, which is also dependent on operator's dexterity. Here, we take the specific training and simulation into consideration. This article aims to describe every step of the manufacture of a new multi-purpose low-cost animal bench-model, with the support of video and images, and to obtain an opinion about the quality of this model by administering a questionnaire to professionals with experience in the procedures. 
Ten experts in the technique were enrolled. The model scored an average of 3.45/5 for its anatomical realism; 4.75/5 for its usefulness as a training tool for simulation courses and assessments. The time necessary to build the model was 15 minutes, and the cost amounted to 10&#8364;. The animal bench-model was considered a very useful simulator for tracheostomy training and assessments. Therefore, it could be used as a tool for medical courses and residencies.

This article illustrates every step of the manufacture of a new multi-purpose low-cost animal bench-model for subglottic airway access management. All the procedures are shown in the video. The model's realism and its suitability for training the given clinical maneuvers were assessed by independent senior otolaryngologists and anesthesiologists.

一种用于气管造口术教学的多功能低成本动物模型的制作

Tracheostomy is one of the most frequent procedures, performed through various techniques in the intensive care unit and emergency situations. Despite ...