目前的研究是由Solorz-扎克研究基金会资助的。

所有的手术均受到伦理审查和批准上巴伐利亚行政区政府（编号:55.2-1-54-2532.3-13-13和-2532-136-11）。动物是雄性C57BL / 6小鼠体重约25g。 1。动物的制备<ol><li>通过将鼠标变成室内诱导麻醉。冲洗室用5％异氟醚，直到动物失去意识。 </li><li>预混注入腹腔麻醉:芬太尼（0.05毫克/千克），咪达唑仑（5毫克/千克）和托咪定（0.5毫克/千克）。在手术过程中之前并定期检查反射。再注入初始量的三分之一每小时维持麻醉。 </li><li>从一个20 G静脉导管11做了一个管插管经口气管。插管固定在倾斜平台（30°）的动物，收回舌头弯曲镊子，可视化操作显微镜下声带和管子插入气管在灵感。 </li><li>鼠标放置在俯卧位，并检查管的正确位置用棉片或microcapnograph。 </li><li>在插管连接到呼吸面罩。通风鼠标与室内空气辅以25％的氧气以180-220次/分和200-250微升的每搏输出量的频率。 </li><li>插管管连接到microcapnograph。通过调节换气次数维持呼气末二氧化碳分压在30毫米汞柱。 </li><li>插入直肠温度探头，并将该动物上的加热垫，以保持37℃的体温。 </li><li>适用的环状pulsoximeter传感器上的右后爪。 </li><li>打开用剪刀的头骨上面的皮肤。切口应大约0.5厘米长，耳朵和眼睛之间。 </li><li>解剖与颞骨手术刀左侧颞肌。 </li><li>胶水激光多普勒血流仪（LDF）探头上左颞骨。持探针在固定位置，直到胶硬化。 </li><li>钻头的直径约1.5孔用牙钻成左颞骨。用生理盐水冷却骨，以防止热损伤。 </li><li>将ICP探头插入颅腔。推进以背部尽可能防止脑组织损伤和出血。 </li><li>如果探头是在正确的位置，固定，并用水泥密封。让水泥干燥5分钟。 </li><li>将鼠标仔细仰卧位。 </li><li>对于连续血压监测，导尿左股动脉。 </li><li>股骨导管连接到血压监测装置。 </li></ol> 2。 SAH诱导<ol><li>打开用剪刀从胸骨到下巴（2公分）的皮肤。解剖结缔组织直言，推动唾液腺一边。 </li><li>暴露左颈总动脉（CCA），并动员了。保存迷走神经，它运行在相同的结缔组织鞘为CCA。移动颅和揭露和调动使用相同的技术在ICA和ECA。 </li><li>结扎ECA尽量颅越好。 </li><li>预先安排周围的非洲经委会灯丝两个结扎。 </li><li>与microclips闭塞CCA和ICA的暂时。定位与microclip敷贴microclips。确保销子被轻轻拉起他们回到正确应用。 </li><li>切为细丝插入到非洲经委会同一个容器剪了一个洞。 </li><li>插入普理灵5-0长丝12毫米长到非洲经委会。 </li><li>有一个预先安排结扎关闭插入位点。 </li><li>从CCA和ICA的一个microclip喷头拆下microclips。 </li><li>推进灯丝用钳子插入ICA直到ICP升高。对ICP的突然崛起表明出血感应。 </li><li>立即撤销灯丝和关闭两个公关结扎ECAearranged结扎连续。这可以防止渗出的插入位点。 </li><li>缝合皮肤伤口。 </li><li>监测动物的另外20分钟的生理学参数。 </li><li>移去ICP和LDF探头和缝合皮肤伤口。 </li></ol> 3。实验结束<ol><li>用20毫升生理盐水（室温）的随后加20ml 4％PFA的PBS（4℃）transcardially灌注动物。 </li><li>解剖出脑颅骨。切开颅骨中线和轨道腔之间。然后从脑剥骨。 </li><li>评估蛛网膜下腔血液分布。 </li></ol> 4。在生存手术案例的思考（而不是在视频中所示） <ol><li>后直接麻醉诱导注射卡洛芬（4毫克/公斤皮下注射）用于术后镇痛。在术后观察期间卡洛芬（4毫克/公斤皮下）注射每24小时。 </li&gt; <li>相反创血压测量使用无创血压监测系统。 </li><li>终止注射麻醉剂拮抗皮下:纳洛酮（1.2毫克/千克），氟马西尼（0.5毫克/千克）和阿替美唑（2.5毫克/千克）。 </li><li>拔管的动物。 </li><li>反射恢复后，把动物带进预热室。保持动物在约32℃下24小时。 </li><li>动物被用于在手术后的第一个小时自主呼吸和全身情况定期检查。如果脑干受影响的动物已经呼吸困难，应实施安乐死。 </li><li>动物是他们的一般状况和体重，以及对神经系统和感觉障碍15日常检查。 </li></ol>

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作者什么都没有透露。

蛛网膜下腔出血后的治疗方案是稀缺的，大多inefficacious。因此需要后出血性脑损伤的病理生理机制还有待进一步了解，以确定新的治疗靶点，开发新的治疗方法。标准化和转基因动物， 如小鼠，重现性好动物模型对于这样的调查是至关重要的。该CWP模式已经成为一种广泛使用的型号为蛛网膜下腔出血，因为它类似于人类中的病理生理密切，但是，它在小鼠的使用是由低重复性和高际变化?...

蛛网膜下腔出血是脑卒中亚型的患者最少的有利结果 ​​:出血后1个月内的患者40％死亡，幸存者很少有临床有利的结果。 绝大多数自发SAHS（80％）是由颅内动脉瘤，沿前，后交通动脉，基底动脉和大脑中动脉（MCA）2大多位于破裂引起的。 这样的动脉瘤是困难的动物模型，因此，蛛网膜下腔出血动物模型中，不是由注入的血液进行进入蛛网膜下腔/脑室或蛛网膜下腔血管腔内穿孔。 自体血注入枕大池是容易执行和可重复性的血容量可直接控制3。不幸的是，蛛网膜下腔出血病理生理机制的某些方面， 例如:血管损伤，不能由该程序进行建模。诱导SAH的另一种技术方法是一种脑池内静脉4的开口。 然而，所述管腔内CWP在MCA分支似乎是过程，模型在人类的病理生理学最密切5。该方法被开发和大鼠首先描述由Bederson等人，并在同一时间通过Veelken和同事6,7。后来腔内穿孔模型适应于小鼠8,9。灯丝被插入到颈外动脉（ECA）和通过内颈动脉（ICA）推进到颅底。在MCA的分支点处的灯丝刺穿容器和诱导出血进入蛛网膜下腔的颅底。血液然后分发到沿裂缝和血管的剩余蛛网膜下腔。出血是由血凝块形成在穿孔的部位停止了，但rebleedings，WHICH往往是不利的患者10，就可能发生。因此，血管内纤维模型在过去的几年中成为一种广泛使用的SAH模型。最经常提到的缺点灯丝穿孔模型的是，出血量不能直接控制，因此可能是可变的。这种变化可以显著由动物生理学和后出血ICP严格控制减少。 老鼠有很大的优势可用大量转基因株。然而，由于它们的小尺寸的外科手术往往比在较大的物种， 例如大鼠或兔子更加复杂。因此，对于大鼠小鼠开发的技术的按比例缩小往往不会导致所期望的结果， 例如为小鼠具有非常有限的体重和血液量的非侵入性技术血压和血液气体分析以及对血红蛋白饱和度和心脏速率监测必须施加只要有可能。因此，当前出版物的目的是描述灯丝穿孔模型的蛛网膜下腔出血小鼠和演示了如何这种模式可以在一个标准化的和高度可重复的方式进行。

<table border="1">
	<tbody>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td>Equipment</td>
		</tr>
		<tr>
			<td>operation microscope</td>
			<td>Leica</td>
			<td>KL2500</td>
			<td></td>
		</tr>
		<tr>
			<td>isoflurane vaporizer</td>
			<td>Harvard Instruments</td>
			<td>Continuous Flow Vaporizer</td>
			<td></td>
		</tr>
		<tr>
			<td>respirator</td>
			<td>Hugo Sachs</td>
			<td>Minivent 845</td>
			<td></td>
		</tr>
		<tr>
			<td>microcapnograph</td>
			<td>Hugo Sachs</td>
			<td>Type 340</td>
			<td></td>
		</tr>
		<tr>
			<td>temperature controller</td>
			<td>FHC</td>
			<td>DC Temperature Controller</td>
			<td></td>
		</tr>
		<tr>
			<td>dental drill</td>
			<td>Paggen</td>
			<td>Labset- N</td>
			<td></td>
		</tr>
		<tr>
			<td>ICP monitor</td>
			<td>Codman</td>
			<td>ICP monitor</td>
			<td></td>
		</tr>
		<tr>
			<td>blood pressure monitor</td>
			<td>AD Instruments</td>
			<td>Bridge Amp FE221</td>
			<td></td>
		</tr>
		<tr>
			<td>syringe pump</td>
			<td>World Precision Instruments</td>
			<td>SP101IZ</td>
			<td></td>
		</tr>
		<tr>
			<td>pulsoximeter</td>
			<td>Kent Scientific</td>
			<td>MouseSTAT</td>
			<td></td>
		</tr>
		<tr>
			<td>LDF</td>
			<td>Perimed</td>
			<td>Periflux 5000</td>
			<td></td>
		</tr>
		<tr>
			<td>analog data monitor</td>
			<td>AD Instruments</td>
			<td>Power Lab 16/35</td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td>Material</td>
		</tr>
		<tr>
			<td>cement for ICP probe fixation</td>
			<td>Speiko</td>
			<td>Carboxylate cement</td>
			<td></td>
		</tr>
		<tr>
			<td>glue for LDF probe fixation</td>
			<td>Bob Smith Industries</td>
			<td>Cyanoacrylate glue (Maxi Cure and Insta Set)</td>
			<td></td>
		</tr>
		<tr>
			<td>venous catheter</td>
			<td>Johnson &#38; Johnson</td>
			<td>Jelco winged i.v. catheter; REF 4076</td>
			<td>modified intubation tube</td>
		</tr>
		<tr>
			<td>tubing for femoral catheter</td>
			<td>Smiths Medical</td>
			<td>Fine Bore Polythene Tubing; ID 0.28 mm OD 0.61 mm; REF 800/100/100</td>
			<td>cut to 30 cm length</td>
		</tr>
		<tr>
			<td>filament for vessel perforation</td>
			<td>Ethicon</td>
			<td>Prolene 5-0</td>
			<td>cut to 12 mm length</td>
		</tr>
		<tr>
			<td>surgical equipment</td>
			<td>Fine Scientific Instruments</td>
			<td>forceps medical #5, vessel scissors 8 cm, microclip 4 mm jaw</td>
			<td></td>
		</tr>
	</tbody>
</table>

a murine model of subarachnoid hemorrhage

在这个视频发布蛛网膜下腔出血（SAH）的标准化小鼠模型。出血是由威利斯穿孔（CWP）的血管内圆和诱发颅内压（ICP）监测证实。从而在周围动脉循环蛛网膜下腔空间和小脑裂隙均匀血液分布的实现。体温升高，全身血压，心脏速率和血红蛋白饱和度:动物生理学是通过气管插管，机械通气，并连续在线监测的各种生理和心血管参数维护。由此，脑灌注压可以紧密监视导致淤血较少可变容积。这允许一个更好的标准化小鼠血管内丝穿孔，使整个模型高度重复性。因此，它是现成的野生型和遗传学药理和病理生理研究LY基因小鼠。

死亡一旦手术技术掌握过程不会引起任何术中死亡。出血也可在几乎所有的动物来实现。术后死亡率为30-40％，与大多数动物死在术后第1天（ 图5）。 SAH后ICP值出血前的ICP约为4毫米汞柱。在ICP的急剧增加高达120毫米汞柱出血的效果。 ICP值，然后在5分钟内，大约30毫米汞柱（ 图1）稳定。在24小时出血ICP备后仍有?...

Watch this Scientific Journal Video about A Murine Model of Subarachnoid Hemorrhage at JoVE.com

A Murine Model of Subarachnoid Hemorrhage

蛛网膜下腔出血的威利斯穿孔腔内圆一个标准化的小鼠模型进行描述。血管穿孔和蛛网膜下腔出血是由颅内压监测监控。除了各种重要的参数被记录和控制，以保持生理条件。

蛛网膜下腔出血的小鼠模型

In this video publication a standardized mouse model of subarachnoid  hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of  Willis ...

a-murine-model-of-subarachnoid-hemorrhage

Research

JoVE Journal

Medicine

19.5K 次观看.  University of Munich Medical Center. 蛛网膜下腔出血的威利斯穿孔腔内圆一个标准化的小鼠模型进行描述。血管穿孔和蛛网膜下腔出血是由颅内压监测监控。除了各种重要的参数被记录和控制，以保持生理条件。 

视频: A Murine Model of Subarachnoid Hemorrhage

A Low Mortality Rat Model to Assess Delayed Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage

Objective: To characterize and establish a reproducible model that demonstrates delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) in rats, in order to identify the initiating events, pathophysiological changes and potential targets for treatment.
Methods: Twenty-eight male Sprague-Dawley rats (250 - 300 g) were arbitrarily assigned to one of two groups - SAH or saline control. Rat subarachnoid hemorrhage in the SAH group (n=15) was induced by double injection of autologous blood, 48 hr apart, into the cisterna magna. Similarly, normal saline (n=13) was injected into the cisterna magna of the saline control group. Rats were sacrificed on day five after the second blood injection and the brains were preserved for histological analysis. The degree of vasospasm was measured using sections of the basilar artery, by measuring the internal luminal cross sectional area using NIH Image-J software. The significance was tested using Tukey/Kramer's statistical analysis.
Results: After analysis of histological sections, basilar artery luminal cross sectional area were smaller in the SAH than in the saline group, consistent with cerebral vasospasm in the former group. In the SAH group, basilar artery internal area (.056 &mu;m &plusmn; 3) were significantly smaller from vasospasm five days after the second blood injection (seven days after the initial blood injection), compared to the saline control group with internal area (.069 &plusmn; 3; p=0.004). There were no mortalities from cerebral vasospasm.
Conclusion: The rat double SAH model induces a mild, survivable, basilar artery vasospasm that can be used to study the pathophysiological mechanisms of cerebral vasospasm in a small animal model. A low and acceptable mortality rate is a significant criterion to be satisfied for an ideal SAH animal model so that the mechanisms of vasospasm can be elucidated 7, 8. Further modifications of the model can be made to adjust for increased severity of vasospasm and neurological exams.

Aneurysmal subarachnoid hemorrhage (SAH) is bleeding that occurs into the subarachnoid space when an aneurysm ruptures. While the morbidity and mortality from this event has been on a decline due to improved treatment approaches, the risk of vasospasm after subarachnoid hemorrhage continues to be the same as it was several years ago. The importance of establishing a comprehensive and reproducible animal model to identify initiating events of cerebral vasospasm has been the focus of research since the first use of rats in an experimental vasospasm model in 1979 by Barry et al. Early work in rats demonstrated that a single injection of autologous blood into the cisterna magna led to acute (within minutes) but not delayed cerebral vasospasm 3, 6, 14. Here we characterize a low mortality SAH rat model that results in reproducible delayed vasospasm.

死亡率低大鼠模型的实验性蛛网膜下腔出血后迟发性脑血管痉挛评估

Objective: To characterize and establish a reproducible model that demonstrates delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) ...

科研

医学

Murine Model of Wound Healing

Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. Impaired wound healing, which occurs in diabetic patients for example, can lead to severe unfavorable outcomes such as amputation. There is, therefore, an increasing impetus to develop novel agents that promote wound repair. The testing of these has been limited to large animal models such as swine, which are often impractical. Mice represent the ideal preclinical model, as they are economical and amenable to genetic manipulation, which allows for mechanistic investigation. However, wound healing in a mouse is fundamentally different to that of humans as it primarily occurs via contraction. Our murine model overcomes this by incorporating a splint around the wound. By splinting the wound, the repair process is then dependent on epithelialization, cellular proliferation and angiogenesis, which closely mirror the biological processes of human wound healing. Whilst requiring consistency and care, this murine model does not involve complicated surgical techniques and allows for the robust testing of promising agents that may, for example, promote angiogenesis or inhibit inflammation. Furthermore, each mouse acts as its own control as two wounds are prepared, enabling the application of both the test compound and the vehicle control on the same animal. In conclusion, we demonstrate a practical, easy-to-learn, and robust model of wound healing, which is comparable to that of humans.

A murine model of cutaneous wound healing that can be used to assess therapeutic compounds in physiological and pathophysiological settings.

伤口愈合的小鼠模型

Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. ...

A New Murine Model of Endovascular Aortic Aneurysm Repair

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of Abdominal aortic aneurysm (AAA) pathophysiology. There is no abdominal aortic aneurysm endograft exclusion model cheap and reproducible, which would allow deep investigations of AAA before and after treatment. We hereby describe how to induce, and then to exclude with a covered coronary stentgraft an abdominal aortic aneurysm in a rat. The well known elastase induced AAA model was first reported in 19901 in a rat, then described in mice2. Elastin degradation leads to dilation of the aorta with inflammatory infiltration of the abdominal wall and intra luminal thrombus, matching with human AAA. Endovascular exclusion with small covered stentgraft is then performed, excluding any interactions between circulating blood and the aneurysm thrombus. Appropriate exclusion and stentgraft patency is confirmed before euthanasia by an angiography thought the left carotid artery. Partial control of elastase diffusion makes aneurysm shape different for each animal. It is difficult to create an aneurysm, which will allow an appropriate length of aorta below the aneurysm for an easy stentgraft introduction, and with adequate proximal and distal neck to prevent endoleaks. Lots of failure can result to stentgraft introduction which sometimes lead to aorta tear with pain and troubles to stitch it, and endothelial damage with post op aorta thrombosis. Giving aspirin to rats before stentgraft implantation decreases failure rate without major hemorrhage. Clamping time activates neutrophils, endothelium and platelets, and may interfere with biological analysis.

Histological and biochemical modifications after aneurysm endograft exclusion are still unclear. We describe a new model of endograft implantation on a murine aneurysm. Through thrombus analysis with and without persistant circulating blood stream interface, and new endovascular biomaterials evaluation, this model will help to better understand endovascular aneurysm exclusion pathobiology.

一种新的小鼠模型主动脉瘤腔内修复

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of ...

Intrastriatal Injection of Autologous Blood or Clostridial Collagenase as Murine Models of Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a common form of cerebrovascular disease and is associated with significant morbidity and mortality. Lack of effective treatment and failure of large clinical trials aimed at hemostasis and clot removal demonstrate the need for further mechanism-driven investigation of ICH. This research may be performed through the framework provided by preclinical models. Two murine models in popular use include intrastriatal (basal ganglia) injection of either autologous whole blood or clostridial collagenase. Since, each model represents distinctly different pathophysiological features related to ICH, use of a particular model may be selected based on what aspect of the disease is to be studied. For example, autologous blood injection most accurately represents the brain&#39;s response to the presence of intraparenchymal blood, and may most closely replicate lobar hemorrhage. Clostridial collagenase injection most accurately represents the small vessel rupture and hematoma evolution characteristic of deep hemorrhages. Thus, each model results in different hematoma formation, neuroinflammatory response, cerebral edema development, and neurobehavioral outcomes. Robustness of a purported therapeutic intervention can be best assessed using both models. In this protocol, induction of ICH using both models, immediate post-operative demonstration of injury, and early post-operative care techniques are demonstrated. Both models result in reproducible injuries, hematoma volumes, and neurobehavioral deficits. Because of the heterogeneity of human ICH, multiple preclinical models are needed to thoroughly explore pathophysiologic mechanisms and test potential therapeutic strategies.

Preclinical models of intracerebral hemorrhage are utilized to mimic certain aspects of clinical disease. Thus, mechanisms of injury and potential therapeutic strategies may be explored. In this protocol, two models of intracerebral hemorrhage are described, intrastriatal (basal ganglia) injections of autologous blood or collagenase.

自体血液或梭菌胶原酶脑内注射为脑出血的小鼠模型

Intracerebral hemorrhage (ICH) is a common form of cerebrovascular disease and is associated with significant morbidity and mortality. Lack of effective ...

A Preclinical Murine Model of Hepatic Metastases

Numerous murine models have been developed to study human cancers and advance the understanding of cancer treatment and development. Here, a preclinical, murine pancreatic tumor model of hepatic metastases via a hemispleen injection of syngeneic murine pancreatic tumor cells is described. This model mimics many of the clinical conditions in patients with metastatic disease to the liver. Mice consistently develop metastases in the liver allowing for investigation of the metastatic process, experimental therapy testing, and tumor immunology research.

A preclinical, murine model of hepatic metastases performed via a hemispleen injection technique.

肝转移的临床前小鼠模型

Numerous murine models have been developed to study human cancers and advance the understanding of cancer treatment and development. Here, a preclinical, ...

The Rabbit Blood-shunt Model for the Study of Acute and Late Sequelae of Subarachnoid Hemorrhage: Technical Aspects

Early brain injury and delayed cerebral vasospasm both contribute to unfavorable outcomes after subarachnoid hemorrhage (SAH). Reproducible and controllable animal models that simulate both conditions are presently uncommon. Therefore, new models are needed in order to mimic human pathophysiological conditions resulting from SAH.
This report describes the technical nuances of a rabbit blood-shunt SAH model that enables control of intracerebral pressure (ICP). An extracorporeal shunt is placed between the arterial system and the subarachnoid space, which enables examiner-independent SAH in a closed cranium. Step-by-step procedural instructions and necessary equipment are described, as well as technical considerations to produce the model with minimal mortality and morbidity. Important details required for successful surgical creation of this robust, simple and consistent ICP-controlled SAH rabbit model are described.

The experimental intracranial pressure-controlled blood shunt subarachnoid hemorrhage (SAH) model in the rabbit combines the standard procedures &#8212; subclavian artery cannulation and transcutaneous cisterna magna puncture, which enables close mimicking of human pathophysiological conditions after SAH. We present step-by-step instructions and discuss key surgical points for successful experimental SAH creation.

蛛网膜下腔出血急性和后遗症的研究兔血分流型号:技术问题

Early brain injury and delayed cerebral vasospasm both contribute to unfavorable outcomes after subarachnoid hemorrhage (SAH). Reproducible and ...

A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction

Obstruction of the kidney may affect native or transplanted kidneys and results in kidney injury and scarring. Presented here is a model of obstructive nephropathy induced by unilateral ureteric obstruction (UUO), which can either be irreversible (UUO) or reversible (R-UUO). In the irreversible UUO model, the ureter may be obstructed for variable periods of time in order to induce increasingly severe renal inflammation and interstitial fibrotic scarring. In the reversible R-UUO model the ureter is obstructed to induce hydronephrosis, tubular dilation and inflammation. After a suitable period of time the ureteric obstruction is then surgically reversed by anastomosis of the severed previously obstructed ureter to the bladder in order to allow complete decompression of the kidney and restoration of urinary flow to the bladder. The irreversible UUO model has been used to investigate various aspects of renal inflammation and scarring including the pathogenesis of disease and the testing of potential anti-inflammatory or anti-fibrotic therapies. The more challenging model of R-UUO has been used by some investigators and does offer significant research potential as it allows the study of inflammatory and immune processes and tissue remodeling in an injured and scarred kidney following the removal of the injurious stimulus. As a result, the R-UUO model offers investigators the opportunity to explore the resolution of kidney inflammation together with key aspects of tissue repair. These experimental models are of relevance to human disease as patients often present with obstruction of the renal tract that requires decompression and are commonly left with significant residual kidney impairment that has no current treatment options and may lead to eventual end stage kidney failure.

The murine model of irreversible unilateral ureteric obstruction (UUO) is presented together with the model of reversible UUO in which the ureteric obstruction is relieved by anastomosis of the severed ureter into the bladder. These models enable the study of renal inflammation and scarring as well as tissue remodeling.

的不可逆和可逆单侧输尿管梗阻小鼠模型

Obstruction of the kidney may affect native or transplanted kidneys and results in kidney injury and scarring. Presented here is a model of obstructive ...

Pre-clinical Orthotopic Murine Model of Human Prostate Cancer

To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model.

Prostate cancer is the second most common cause of cancer-related deaths in the United States. An orthotopic cancer model provides a useful approach to understand the biology of prostate cancer and to evaluate the efficacy of therapeutic regimens. This protocol describes detailed steps necessary to establish an orthotopic prostate cancer mouse model.

人前列腺癌的临床前原位小鼠模型

To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information ...

Integrated Compensatory Responses in a Human Model of Hemorrhage

Hemorrhage is the leading cause of trauma-related deaths, partly because early diagnosis of the severity of blood loss is difficult. Assessment of hemorrhaging patients is difficult because current clinical tools provide measures of vital signs that remain stable during the early stages of bleeding due to compensatory mechanisms. Consequently, there is a need to understand and measure the total integration of mechanisms that compensate for reduced circulating blood volume and how they change during ongoing progressive hemorrhage. The body&#39;s reserve to compensate for reduced circulating blood volume is called the &#39;compensatory reserve&#39;. The compensatory reserve can be accurately evaluated with real-time measurements of changes in the features of the arterial waveform measured with the use of a high-powered computer. Lower Body Negative Pressure (LBNP) has been shown to simulate many of the physiological responses in humans associated with hemorrhage, and is used to study the compensatory response to hemorrhage. The purpose of this study is to demonstrate how compensatory reserve is assessed during progressive reductions in central blood volume with LBNP as a simulation of hemorrhage.

The purpose of this protocol is to demonstrate the techniques for measuring compensatory responses to reduced central blood volume using lower body negative pressure as a noninvasive experimental model of human hemorrhage which can be used to quantify the total integration of compensatory mechanisms to blood volume deficit in humans.

在出血的人体模型集成的代偿反应

Hemorrhage is the leading cause of trauma-related deaths, partly because early diagnosis of the severity of blood loss is difficult. Assessment of ...

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 ...