Name: a mouse model of fatigue induced by peripheral irradiation
Uploaded: 2017-03-17T14:00:00.000+00:00
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笔者想感谢美国国立卫生研究院的国家心，肺和血液研究所（NHLBI）（NIH）的米歇尔·艾伦慷慨地分享她的专业知识在小鼠表型的方法和她持续不断的技术援助，以及为NHLBI的蒂莫西·亨特帮助我们开发出屏蔽装置。这项研究是由美国国立卫生研究院的护理研究和验证试验的一部分国立研究所院内研究司的支持是通过从肿瘤护理学会基金资助。

伦理学声明:本研究得到了美国国立卫生研究院（NIH）的动物护理和使用委员会。所有参与动物处理和研究成果衡量调查人员通过适当的动物护理和使用的NIH办公室和国家心脏，肺和血液研究所小鼠表型的核心培训。动物试验，住房，并在此研究中使用的环境条件各方面均符合本指南的护理和使用实验动物11。 1.住房和实验动物注:房屋雄性C57BL / 6小鼠（到达后约5周龄）分别在整个实验，并提供食物和水随意存取。所有笼保持在12:12小时亮 - 暗循环的光照阶段开始于早上6点和黑暗阶段在下午6点。 <ol><li>确定老鼠并将它们分配到各个标准通风D鼠标笼。允许恢复识别程序后24小时。 注:尾纹身被推荐作为一种识别手段，以消除耳标可能会陷入一个跑轮的可能性。纹身上每只小鼠的尾部的数字，在尾巴匹配写在小鼠的笼的数目。 </li><li>允许小鼠适应它们的笼子至少三天，轻轻处理每只小鼠的期间每天三分钟。 </li></ol> 2.运行轮驯化和基准<ol><li>引入小鼠个体VWRA笼，每个配备有连接到连续记录的电子计数器跑轮。 注:所有轮计数器通过一个USB接口连接到电脑（请参阅材料清单）。计算机软件计算车轮的转数，行驶距离，和平均速度在整个指定的总所需时间的每一个指定的时间间隔ñ。一旦录音停止，数据将自动两种文本和电子表格保存。 </li><li>通过计算机软件接口发起VWRA的记录。设定记录间隔一小时的持续时间，以至少五天。继续录制VWRA至少五天。 注:在步骤2.2的结束时，所有的小鼠应达到每日车轮运行的活动的相对一致的量。如果没有，那么识别和排除任何异常值。 </li><li>停止VWRA通过软件界面记录和老鼠返回（不运行轮笼）步骤描述1.1标准的笼子。 </li><li>小鼠随机进入任一假照控制或照射组。 </li></ol> 3.辐照注:执行对所有小鼠以下步骤两组，每天一次为三个连续天。每天在相同的顺序处理的小鼠。 <ol><li>通过腹腔注射麻醉每只小鼠氯胺酮（100毫克/千克）和赛拉嗪（10毫克/千克）的混合物。 </li><li>确认麻醉用脚趾捏和使用软膏的眼睛，防止干燥时的麻醉下。 </li><li>转移麻醉鼠标变成铅屏蔽设备。安排在屏蔽鼠标以便只有下腹部/骨盆区域露出。 注:屏蔽由两个率先"盒子"，在两者之间，使辐射照射到鼠标的一个小的，有针对性的区域狭窄的空地上（ 见图1）。 </li><li>用医用胶布鼠标尾部的固定底座在屏蔽范围内的位置。 注意:步骤3.4是可选的，但这样做可以帮助确保鼠标的位置在以下步骤不改变。 </li><li>传输屏蔽装置进入照射器，确保在屏蔽内的动物的位置被保持。 </li><li>如果鼠标是照射组，提供800 cGy的在DOS约110 cGy的/分ê率。如果鼠标是假照对照组中，离开鼠标的等效时间不活动的辐射。 注:最佳辐照设置将取决于特定的设备上。的从137铯源递送110 cGy的/分钟的剂量率是此处所用的辐照的中心的剂量率。曝光时间调节至达到800 cGy的所期望的总剂量。 </li><li>从辐射和屏蔽取出小鼠，然后将其返回到在步骤1.1中提到其原始的，标准笼。 </li><li>连续监视鼠标，直到它已经恢复了足够的意识，以保持胸骨斜卧。 </li></ol> 4.辐射性疲劳测量<ol><li>上的照射连续三天结束后的第二天，将小鼠转移到在步骤2.1中描述他们的个人VWRA笼中。 </li><li>记录VWRA，如在步骤2.2中所述，除了这里设置记录持续时间超过15天。在15天结束时，手动停止VWRA通过软件界面记录。 注意:从各记录期间的数据被自动保存为电子表格，每一个包括旋转，距离和速度在整个记录期间所有动物（列），并在所有的时间间隔（行）的测量。在实验结束时，存在由该记录软件产生两个电子表格:一个用于照射预VWRA，和一个用于辐照后VWRA。 </li></ol>

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这项研究是由院内研究，护理研究的研究所，美国国立卫生研究院的支持部门。

我们已经描述了使用靶向外围照射到在小鼠中诱导的减少VWRA而不混淆发病率或死亡率的协议。重要的是，一个简单的屏蔽装置允许照射在这个协议始终如一的目标期望的区域，通过模仿患者盆腔癌接受放射治疗。相反，涉及大脑和全身照射8，9现有车型CRF，这个模型探讨了周边针对性的照射过程如何影响集中驱动的疲劳性能。在我们的代表性的结果，?...

癌症有关的疲劳（CRF）是一个令人痛心的和昂贵的条件下，往往会影响接受癌症治疗1例。疲劳既不是正比于最近的活动，也没有由其余减轻，并且它与各种相关的情绪，动机，注意力障碍的相关联，并且认知2。 CRF的生物原因是未知的，尽管它已经在许多情况下，已显示在某些情况下，血红蛋白水平和各种激素系统的功能与炎症和细胞因子水平相关联，还（参见Saligan 等人 3的生物审查CRF的研究）。 利用动物模型的对照研究必须要了解这个复杂的条件相关联的行为和生物学。而肿瘤相关4或化疗相关5,6脂肪igue已在啮齿动物模型进行了研究，CRF的病因可能是治疗特定的。为了调查有关放射治疗CRF，我们的小组最近开发的辐射性疲劳7的小鼠模型。在对比涉及脑或全身照射8,9现有的CRF的模型，该模型探讨如何在中央驱动行为的变化，如疲劳，可通过外周定位的照射过程触发。 此处描述的方法被设计成施用于患者的盆腔癌症放射疗法的模型，使用铅屏蔽定位与照射下腹部/骨盆区域。然而，通过修改铅屏蔽​​或其相对于实验动物的位置，这过程可适于建模的身体的其他部分的照射。自愿车轮运行的活动（VWRA）被用来测量疲劳状behavio- [R;因为它是一个自愿的，正常的行为10，它应该允许同时使用其他行为和生物试验。我们已经发现，外围照射足以降低VWRA小鼠而不引起明显的发病率7。与这个模型以后的实验可能有助于揭示免疫和其他生物信号的外围照射，以及在能够产生与CRF相关的赤字中枢神经系统下游的变化的影响。

<table><tbody><tr><td>C57BL/6 Mice</td><td>Charles River</td><td></td><td>Strain code 027 (http://www.criver.com/products-services/basic-research/find-a-model/c57bl-6n-mouse)</td></tr><tr><td>Ketamine HCl</td><td>Putney</td><td></td><td>100 mg/mL stock solution</td></tr><tr><td>Xylazine HCl</td><td>Lloyd Laboratories</td><td></td><td>100 mg/mL stock solution</td></tr><tr><td>Rodent Tattoo System</td><td>AIMS</td><td>ATS-3</td><td>http://animalid.com/lab-animal-identification-systems/ats-3-general-rodent-tattoo-system</td></tr><tr><td>Lead Shielding Apparatus</td><td>(custom made)</td><td></td><td>One-inch thick lead shielding arranged as two boxes with a one-inch thick gap between them for targeted irradiation</td></tr><tr><td>Plexiglass shielding container</td><td>(custom made)</td><td></td><td>Plexiglass container filled with styrofoam. Styrofoam cutouts hold the lead shielding in place.</td></tr><tr><td>GammaCell 40 Exactor</td><td>Best Theratronics</td><td></td><td>http://www.theratronics.ca/product_gamma40.html</td></tr><tr><td>RAD Disk Ultra</td><td>Best Theratronics</td><td></td><td>http://www.theratronics.ca/product_rad.html</td></tr><tr><td>Mouse Single Activity Wheel Chamber</td><td>Lafayette Instrument Company</td><td>#80820</td><td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=980</td></tr><tr><td>Activity Wheel Counter for Computer Monitoring</td><td>Lafayette Instrument Company</td><td>#86061</td><td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1052</td></tr><tr><td>Modular Cable for Wheel Counters</td><td>Lafayette Instrument Company</td><td>#86051-7</td><td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1046</td></tr><tr><td>USB Computer Interface for Activity Wheel Counters</td><td>Lafayette Instrument Company</td><td>#86056A</td><td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1047</td></tr><tr><td>Activity Wheel Monitor Software</td><td>Lafayette Instrument Company</td><td>#86065</td><td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1053</td></tr></tbody></table>

a mouse model of fatigue induced by peripheral irradiation

癌症有关的疲劳（CRF）是一个令人痛心的和昂贵的条件下，往往会影响接受癌症治疗，包括放射治疗的病人。在这里，我们描述了使用靶向外围照射到在小鼠中诱导的疲劳样行为的方法。用适当的屏蔽，照射靶向小鼠的下腹部/骨盆区域，不放过脑，以努力模型由与骨盆癌的个体接受放射治疗。我们提供的照射剂量足以诱导小鼠，通过自愿车轮运行的活性（VWRA）测定疲劳样行为，而不引起明显的病态。由于车轮跑在小鼠正常的，自愿的行为，它的使用应该有其他行为测试或生物措施很少混杂效应。因此，车轮的运行可以理解疲劳的行为和生物相关因素可以作为一种可行的测量结果。 CRF是频繁合作复杂条件的并发症，并且可能具有与既癌症和其各种处理的原因。本文介绍的方法是调查的，更普遍的促进CRF的发展辐射引起的变化，探索生物网络，可以解释像疲劳外围触发，但集中驱动行为的发展和维持有用。

小鼠的三个批通过上述协议运行。共有16假和20照射（2 400 cGy的，3×800 cGy的/天）小鼠者。照射后连续三天，照射组有显著减少VWRA相比，假（混合重复测量方差分析:照射治疗，女1,13 = 19.233，P &lt;0.001的主要作用）。效果是前七天显著照射后（简单主效应，P &lt;0.05和Bonferroni校正），与发生在第三天的最低平均VWRA距离辐射（ 图2A）之后。天25和26中，没有...

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A Mouse Model of Fatigue Induced by Peripheral Irradiation

我们描述了使用靶向外围照射到在小鼠中诱导的疲劳样行为的方法。选定的非致命辐射剂量导致自愿轮运行活动为期一周的减少。

疲劳的小鼠模型的外围照射引起

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. ...

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JoVE Journal

Cancer Research

7.8K 次观看.  National Institutes of Health. 我们描述了使用靶向外围照射到在小鼠中诱导的疲劳样行为的方法。选定的非致命辐射剂量导致自愿轮运行活动为期一周的减少。 

视频: A Mouse Model of Fatigue Induced by Peripheral Irradiation

Fluorescent Orthotopic Mouse Model of Pancreatic Cancer

Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will survive longer than five years. In order to understand and mimic the microenvironment of pancreatic tumors, we utilized a murine orthotopic model of pancreatic cancer that allows non-invasive imaging of tumor progression in real time. Pancreatic cancer cells expressing green fluorescent protein (PANC-1 GFP) were suspended in basement membrane matrix, high concentration, (e.g., Matrigel HC) with serum-free media and then injected into the tail of the pancreas via laparotomy. The cell suspension in the high concentration basement membrane matrix becomes a gel-like substance once it reaches room temperature; therefore, it gels when it comes in contact with the pancreas, creating a seal at the injection site and preventing any cell leakage. Tumor growth and metastasis to other organs are monitored in live animals by using fluorescence. It is critical to use the appropriate filters for excitation and emission of GFP. The steps for the orthotopic implantation are detailed in this article so researchers can easily replicate the procedure in nude mice. The main steps of this protocol are preparation of the cell suspension, surgical implantation, and whole body fluorescent in vivo imaging. This orthotopic model is designed to investigate the efficacy of novel therapeutics on primary and metastatic tumors.

A procedure to implant green fluorescent protein-expressing pancreatic cancer cells (PANC-1 GFP) orthotopically into the pancreas of Balb-c Ola Hsd-Fox1nu mice to assess tumor progression and metastasis is presented here.

胰腺癌的荧光原位小鼠模型

Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will ...

科研

癌症研究

Evaluating the Role of Mitochondrial Function in Cancer-related Fatigue

Fatigue is a common and debilitating condition that affects most cancer patients. To date, fatigue remains poorly characterized with no diagnostic test to objectively measure the severity of this condition. Here we describe an optimized method for assessing mitochondrial function of PBMCs collected from fatigued cancer patients. Using a compact extracellular flux system and sequential injection of respiratory inhibitors, we examined PBMC mitochondrial functional status by measuring basal mitochondrial respiration, spare respiratory capacity, and energy phenotype, which describes the preferred energy pathway to respond to stress. Fresh PBMCs are readily available in the clinical setting using standard phlebotomy. The entire assay described in this protocol can be completed in less than 4 hours without the involvement of complex biochemical techniques. Additionally, we describe a normalization method that is necessary for obtaining reproducible data. The simple procedure and normalization methods presented allow for repeated sample collection from the same patient and generation of reproducible data that can be compared between time points to evaluate potential treatment effects.

Our goal was to develop a practical protocol to evaluate mitochondrial dysfunction associated with fatigue in cancer patients. This innovative protocol is optimized for clinical use involving only standard phlebotomy and basic laboratory procedures.

线粒体功能在癌症相关疲劳中的作用评价

Fatigue is a common and debilitating condition that affects most cancer patients. To date, fatigue remains poorly characterized with no diagnostic test to ...

The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of current interventions to adequately treat fatigue in all patients leaves a need for new treatment options. Despite the therapeutic need and importance of preclinical research in helping identify promising novel treatments, few preclinical assays of fatigue are available. Moreover, the most common preclinical assay used to assess fatigue-like behavior, voluntary wheel running, is not suitable for use with some strains of mice, may not be sensitive to drugs that reduce fatigue, and has relatively low throughput. The current protocol describes a novel, non-voluntary preclinical assay of fatigue-like behavior, the treadmill fatigue test, and provides evidence of its efficacy in detecting fatigue-like behavior in mice treated with a chemotherapy drug known to cause fatigue in humans and fatigue-like behavior in animals. This assay may be a beneficial alternative to wheel running, as fatigue-like behavior and potential interventions can be assessed in a greater number of mice over a shorter time frame, thus permitting faster discovery of new therapeutic options.

Fatigue is a common, undertreated and frequently poorly-understood symptom in many diseases and disorders. New preclinical assays of fatigue may help to improve current understanding and future treatment of fatigue. To that end, the current protocol provides a novel means of measuring fatigue-like behavior in the mouse.

跑步机疲劳试验:疲劳类似的行为，为鼠标操作简单，高通量检测

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of ...

行为学

Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition

The functional characterization of adult-born neurons remains a significant challenge. Approaches to inhibit adult neurogenesis via invasive viral delivery or transgenic animals have potential confounds that make interpretation of results from these studies difficult. New radiological tools are emerging, however, that allow one to noninvasively investigate the function of select groups of adult-born neurons through accurate and precise anatomical targeting in small animals. Focal ionizing radiation inhibits the birth and differentiation of new neurons, and allows targeting of specific neural progenitor regions. In order to illuminate the potential functional role that adult hypothalamic neurogenesis plays in the regulation of physiological processes, we developed a noninvasive focal irradiation technique to selectively inhibit the birth of adult-born neurons in the hypothalamic median eminence. We describe a method for Computer tomography-guided focal irradiation (CFIR) delivery to enable precise and accurate anatomical targeting in small animals. CFIR uses three-dimensional volumetric image guidance for localization and targeting of the radiation dose, minimizes radiation exposure to nontargeted brain regions, and allows for conformal dose distribution with sharp beam boundaries. This protocol allows one to ask questions regarding the function of adult-born neurons, but also opens areas to questions in areas of radiobiology, tumor biology, and immunology. These radiological tools will facilitate the translation of discoveries at the bench to the bedside.

The function of adult-born mammalian neurons remains an active area of investigation. Ionizing radiation inhibits the birth of new neurons. Using computer tomography-guided focal irradiation (CFIR), three-dimensional anatomical targeting of specific neural progenitor populations can now be used to assess the functional role of adult neurogenesis.

成人下丘脑神经发生局灶性放射性抑制功能审讯

The functional characterization of adult-born neurons remains a significant challenge. Approaches to inhibit adult neurogenesis via invasive viral ...

神经科学

Establishment of a Robust and Reproducible Model of Radiation-Induced Skin and Muscle Fibrosis

Radiation-induced skin fibrosis (RISF) can result from a plethora of scenarios including cancer therapy, accidental exposure, or acts of terrorism. Radioactive beams can penetrate through the skin and affect the structures in their path including skin, muscles, and internal organs. Skin is the first structure to get exposed to radiation and is susceptible to develop chronic fibrosis, which is challenging to treat. Currently, limited treatment options show moderate efficacy in mitigating radiation-related skin fibrosis. A key factor hindering the development of effective countermeasures is the absence of a convenient and robust model that could allow for translation of the experimental findings to humans. Here, a robust and reproducible murine hind limb skin fibrosis model has been established for prophylactic and therapeutic evaluation of possible agents for functional and molecular recovery.
The right hind limb was irradiated using a single dose of 40 (Gray) Gy to induce skin fibrosis. Subjects developed edema and dermatitis in the early stages proceeded by visible skin constriction. Irradiated limbs showed a significantly reduced limb range of motion in the following weeks. In late stages, acute side effects subsided, yet chronic fibrosis persisted. A gait index was performed as an additional functional assay, which demonstrated the development of functional impairment. These non-invasive methods demonstrated reliable measurements for tracing fibrosis progression, which is supported by histological analyses. The radiation dose, application, and post-irradiation analyses employed in this model offer a vigorous and reproducible method for studying radiation-induced skin fibrosis and testing the efficacy of therapeutical agents.

Here we present a protocol to induce radiation-induced skin fibrosis in the hind limb of mice and perform post-irradiation measurements of chronic impairment via limb excursion and gait index analyses to evaluate the functional outcome. The model elucidates radiation-related skin fibrosis mechanisms and is useful in subclinical therapeutic studies.

Radiation-induced skin fibrosis (RISF) can result from a plethora of scenarios including cancer therapy, accidental exposure, or acts of terrorism. ...

Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model

Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and negatively impact patient quality of life and long term survival. Advances in the understanding of the biological pathways associated with normal tissue toxicities have allowed for the development of interventional drugs, however, current response studies are limited by a lack of quantitative metrics for assessing the severity of skin reactions. Here we present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe the instrumentation design of the DOS system as well as the inversion algorithm for extracting the optical parameters. Finally, to demonstrate clinical utility, we present representative data from a pre-clinical mouse model of radiation induced erythema and compare the results with a commonly employed visual scoring. The described DOS method offers an objective, high through-put evaluation of skin toxicity via functional response that is translatable to the clinical setting.

We present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe DOS instrumentation design, optical parameters extraction algorithms and the animal handling procedures required to yield representative data from a pre-clinical mouse model of radiation induced erythema.

弥漫性光学光谱治疗急性电离辐射引起的皮肤毒性的定量评价使用小鼠模型

Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and ...

医学

A Rat Model of Central Fatigue Using a Modified Multiple Platform Method

In this article, we introduced a rat model of central fatigue using the modified multiple platform method (MMPM). The Multiple Platform box was designed as a water tank with narrow platforms on the bottom. The model rats were put into the tank and stood on the platforms for 14 h (18:00 - 8:00) per day for a consecutive 21 days, with a blank control group set for contrast. At the end of modeling, rats in the model group showed an obvious fatigued appearance. To assess the model, we performed several behavioral tests, including the open field test (OFT), the elevated plus maze (EPM) test, and the exhaustive swimming (ES) test. The results showed that anxiety, spatial cognition impairment, poor muscle performance, and declined voluntary activity presented in model rats confirm the diagnosis of&#160;central fatigue. Changes of the central neurotransmitters also verified the result. In conclusion, the model successfully simulated central fatigue, and future study with the model may help reveal the pathological mechanism of the disease.

Here, we present a protocol to introduce a rat model of central fatigue using the modified multiple platform method (MMPM).

基于改进多平台法的大鼠中心疲劳模型

In this article, we introduced a rat model of central fatigue using the modified multiple platform method (MMPM). The Multiple Platform box was designed ...

A Preclinical Model of Exertional Heat Stroke in Mice

Heat stroke is the most severe manifestation of heat-related illnesses. Classic heat stroke (CHS), also known as passive heat stroke, occurs at rest, whereas exertional heat stroke (EHS) occurs during physical activity. EHS differs from CHS in etiology, clinical presentation, and sequelae of multi-organ dysfunction. Until recently, only models of CHS have been well established. This protocol aims to provide guidelines for a refined preclinical mouse model of EHS that is free from major limiting factors such as the use of anesthesia, restraint, rectal probes, or electric shock. Male and female C57Bl/6 mice, instrumented with core temperature (Tc) telemetric probes were utilized in this model. For familiarization with the running mode, mice undergo 3 weeks of training using both voluntary and forced running wheels. Thereafter, mice run on a forced wheel inside a climatic chamber set at 37.5 &#176;C and 40%-50% relative humidity (RH) until displaying symptom limitation (e.g., loss of consciousness) at Tc of 42.1-42.5 &#176;C, although suitable results can be obtained at chamber temperatures between 34.5-39.5 &#176;C and humidity between 30%-90%. Depending on the desired severity, mice are removed from the chamber immediately for recovery in ambient temperature or remain in the heated chamber for a longer duration, inducing a more severe exposure and a higher incidence of mortality. Results are compared with sham-matched exercise controls (EXC) and/or na&#239;ve controls (NC). The model mirrors many of the pathophysiological outcomes observed in human EHS, including loss of consciousness, severe hyperthermia, multi-organ damage as well as inflammatory cytokine release, and acute phase responses of the immune system. This model is ideal for hypothesis-driven research to test preventative and therapeutic strategies that may delay the onset of EHS or reduce the multi-organ damage that characterizes this manifestation.

The protocol describes the development of a standardized, repeatable, preclinical model of exertional heat stroke (EHS) in mice free from adverse external stimuli such as electric shock. The model provides a platform for mechanistic, preventative, and therapeutic studies.

小鼠劳力性中暑的临床前模型

Heat stroke is the most severe manifestation of heat-related illnesses. Classic heat stroke (CHS), also known as passive heat stroke, occurs at rest, ...

Shocktube 方法模拟小鼠高度重复的低水平爆炸

Modeling Highly Repetitive Low-level Blast Exposure in Mice

Exposure to explosive blasts is a significant risk factor for brain trauma among exposed persons. Although the effects of large blasts on the brain are well understood, the effects of smaller blasts such as those that occur during military training are less understood. This small, low-level blast exposure also varies highly according to military occupation and training tempo, with some units experiencing few exposures over the course of several years whereas others experience hundreds within a few weeks. Animal models are an important tool in identifying both the injury mechanisms and long-term clinical health risks following low-level blast exposure. Models capable of recapitulating this wide range of exposures are necessary to inform acute and chronic injury outcomes across these disparate risk profiles.
Although outcomes following a few low-level blast exposures are easily modeled for mechanistic study, chronic exposures that occur over a career may be better modeled by blast injury paradigms with repeated exposures that occur frequently over weeks and months. Shown here are methods for modeling highly repetitive low-level blast exposure in mice. The procedures are based on established and widely used pneumatic shocktube models of open-field blast exposure that can be scaled to adjust the overpressure parameters and the number or interval of the exposures. These methods can then be used to either enable mechanistic investigations or recapitulate the routine blast exposures of clinical groups under study.

作者聚焦:破译小鼠低水平爆炸暴露的长期影响

Presented here are methods for producing repeated low-intensity blast exposures using mice.

对小鼠高度重复的低水平爆炸暴露进行建模

Exposure to explosive blasts is a significant risk factor for brain trauma among exposed persons. Although the effects of large blasts on the brain are ...

疲劳的小鼠模型的外围照射引起

摘要

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此视频中的章节

胰腺癌的荧光原位小鼠模型

线粒体功能在癌症相关疲劳中的作用评价

跑步机疲劳试验:疲劳类似的行为，为鼠标操作简单，高通量检测

成人下丘脑神经发生局灶性放射性抑制功能审讯

Establishment of a Robust and Reproducible Model of Radiation-Induced Skin and Muscle Fibrosis

弥漫性光学光谱治疗急性电离辐射引起的皮肤毒性的定量评价使用小鼠模型

基于改进多平台法的大鼠中心疲劳模型

小鼠劳力性中暑的临床前模型

对小鼠高度重复的低水平爆炸暴露进行建模

对小鼠高度重复的低水平爆炸暴露进行建模