Name: ferric chloride-induced thrombosis mouse model on carotid artery and mesentery vessel
Uploaded: 2015-06-29T14:00:00
Description: Watch this Scientific Journal Video about Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel at JoVE.com

فإن الكتاب أن نعترف الدعم الفني من الفرح ياو والدكتورة كارين البديل، فضلا عن تمويل من NHMRC وNHF.

تمت الموافقة على جميع التجارب التي تنطوي على الحيوانات من قبل البحوث الطبية ألفريد والمخفر جنة الأخلاقيات الحيوانية التعليم (E / 1534/2015 / B). وأجريت كافة المعالجات الجراحية تحت التخدير الكامل، ولم الحيوانات لا تواجه الألم في أي مرحلة. جميع التجارب وصفها هي عدم استرداد. </...

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وكلوريد الحديديك الناجم عن نموذج تجلط الدم هو أداة بحث ممتازة. كما هو مبين في هذه الدراسة، فمن السهل للغاية لتنفيذ وعندما تستخدم بالاقتران مع intravital المجهري أو دوبلر مقياس الجريان، فإنه يوفر جيد للرصد في الوقت الحقيقي من تشكيل خثرة. ضبط التعرض الوقت وتركيز FeCl 3، ...

دراسة الآليات التي تشارك في تطوير تجلط الدم وتقييم فعالية العقاقير المضادة للالجلطات يتطلب راسخة النماذج الحيوانية التجريبية. وكانت نماذج حيوانية كبيرة أول من استخدامها لأنها توفر السفن الكبيرة أكثر مماثلة على البشر من القوارض 1. ومع ذلك، وارتفاع تكلفة، والمرافق الكبيرة المطلوبة وصعوبة التلاعب بها وراثيا هي العوائق الرئيسية لاستخدامها والحيوانات الكبيرة تقتصر الآن على الدراسات قبل السريرية في وقت متأخر مرة واحدة أعطت الاختبارات الأولية على القوارض نتائج قاطعة 2. مع توافر واسعة من السلالات المعدلة وراثيا وخروج المغلوب وصغر حجمها أن يقلل من كمية المخدرات جرعات اللازمة لفي الجسم الحي اختبار، وتستخدم الفئران أساسا للبحث تجلط الدم. لذلك، تم وضع عدة نماذج من اضطرابات الجلطة في الفئران 3. العديد من النماذج الجلطة التي أنشئت تعطل intimطبقة من جدار الوعاء الدموي، تليها تعرض المصفوفة خارج الخلية البطانية الفرعية لتدفق الدم يحفز تشكيل جلطات الدم 4. والجلطة الدموية قد تنجم عن التعرض الكولاجين الذي يؤدي إلى تنشيط الصفائح الدموية و / أو من التعرض للعامل النسيج الذي ينشط شلال التخثر 5. ثم يتم توظيف العديد من التقنيات لتحقيق إصابة الأوعية الأولية. Pierangeli آخرون بتطوير نموذج تعطل الميكانيكية بأداة المجهرية في الوريد الفخذي 6. Kikushi وآخرون وصفت نموذج الذي يتكون في إدارة صورة مركب تفاعلي (روز البنغال) التي تتراكم في طبقة ثنائية الدهون من الخلايا البطانية التي تتبعها الإثارة محددة من جدار الوعاء الدموي في المصالح مع الضوء الأخضر (540 نانومتر) 7. ويمكن أيضا الإصابة ان يحدثها قصيرة عالية الكثافة نبضة ليزر إضاءة 8. تقنية أخرى أنشئت أولا على الشريان السباتي الفئرانيتكون في التطبيق الموضعي للكلوريد الحديديك (FeCl 3) 9. في هذه الحالة، فإن النتائج سفينة تعرية من الجذور الحرة الناتجة عن FeCl 3 الذي يسبب بيروكسيد الدهون وتدمير الخلايا البطانية 10. إصابة الحث على التعبير عن عدة جزيئات الالتصاق مما اثار التصاق الصفائح الدموية وتجميعها وكذلك الكريات البيض التوظيف. وقد ثبت أن الكريات البيض، ولا سيما العدلات، تلعب دورا حاسما في تفعيل شلال التخثر في الدم مما يؤدي إلى تجلط الدم 11. هذه الطريقة مناسبة تماما لإنتاج شلال التخثر. يجب أن المحققين أن نضع في اعتبارنا أنه في هذا النموذج الماوس، وعادة ما يسببها تجلط الدم في الأوعية صحية في حين تجلط الدم في البشر يحدث بشكل رئيسي في مثل المريضة. سفن تصلب الشرايين. حيث أن هذا النموذج هو بسيط جدا لتنفيذ وفعال أيضا في الفئران، هو الآن في وضع تخثر تستخدم في الغالبلتر بالنسبة للحيوان صغير الدراسات المجراة. بالإضافة إلى ذلك، هذه التقنية توفر إمكانية للحث على تشكيل الجلطات في مجموعة متنوعة من السفن. يمكن السفن المستهدفة هي الشرايين أو الأوردة كبيرة قطرها (الشريان السباتي، الفخذ، الوريد الأجوف) أو القطر الصغير (مساريق، المشمرة) 12-14. وفي الآونة الأخيرة، تم استخدامه أيضا في الشريان الدماغي الأوسط القريبة لتطوير نموذج من السكتة الدماغية 15. تشكيل الجلطة يمكن ملاحظة مباشرة من قبل intravital المجهري بعد وضع العلامات الفلورية من الصفائح الدموية وكريات الدم البيضاء أو مراقبتها عن طريق قياس انخفاض تدفق الدم مع التحقيق في درجة الحرارة أو 12،16،17 دوبلر التحقيق. ويمكن بعد ذلك التحقيق العديد من المعلمات مثل الوقت انسداد، والوقت تشكيل خثرة أو حجم الجلطة. الفروق الفسيولوجية بين السفن التحقيق في نتيجة الاختلافات الكبيرة في الجلطات التي تم الحصول عليها. وبالتالي، والمحققين عادة ما تختار السفينة المستهدفة وفقا لمعايير يريدون measuإعادة و / أو المرض وضع يريدون التحقيق. عادة، ونموذج على الشريان السباتي هو أكثر ملاءمة للبحث عن atherothrombosis المتعلقة احتشاء عضلة القلب أو السكتة الدماغية في حين أن الدراسات على الوريد الأجوف هي أكثر ملاءمة للبحث عن الخثار الوريدي العميق. سهولة الحصول على سفن مختلفة يحدد أيضا الطريقة المستخدمة لقياس النمو الجلطة. على سبيل المثال، والأوعية المساريقي من السهل للوصول إلى صنع هذا النموذج مناسبة تماما لمراقبة مجهرية حيوي داخلي ودراسة ديناميات تشكيل خثرة. الشريان السباتي هو يصعب الوصول إليها ولكن أكبر مما قياس تدفق الدم وتوفر نموذجا ممتازا لدراسة تخثر انسداد. قدمت كلوريد الحديديك نموذج تجلط الدم الناجم عن التقدم الهائل في فهم هذه الحالة المرضية. وقد تم استخدامه في العديد من الدراسات التي تركز على دور عامل فون ويلبراند في تشكيل الجلطة 18،19. جنبا إلى جنب مع مودى الجينيتقنيات fication، وقد سمح ذلك تحديد العديد من الجينات المحددة المعنية في اضطرابات الجلطات. العمراني وآخرون. وقد أظهرت مثلا أن في المغلوب من الجين JAK2 V617F يرتبط مع تشكيل المتسارع للجلطة غير مستقرة 20. تشانغ وآخرون. وقد حققت في تورط الفسيولوجية للمستقبلات P2Y12 الصفائح الدموية وأظهرت أن الفئران المعدلة وراثيا overexpressing على وجه التحديد هذا المستقبل في الصفائح الدموية فقط، عرض تشكيل خثرة أسرع وأكثر استقرارا في الشريان المساريقي أصيب FeCl 3 21. كما تم التحقيق في الدور الحاسم للمنشط البلازمينوجين الأنسجة من نوع (TPA) ويوروكيناز من نوع المنشط plasminogen (ميكرو) في عملية تدهور الليفين في هذه الطريقة 22. وعلاوة على ذلك هذا النموذج يوفر أيضا وسيلة بسيطة ودقيقة لاختبار القدرات الحال للفبرين العديد من الأدوية الجديدة في الجسم الحي. على سبيل المثال، قد استخدمت وانغ وآخرون. هذا النموذج لعشرالبريد التحقق من صحة ما قبل السريرية من رواية المؤتلف منشط البلازمينوجين تستهدف تنشيط الصفائح الدموية 23. كما مكنت هذه الطريقة التحقق من البروتينات العلاجية معزولة عن اللعابية من القراد، الخفافيش مصاصي الدماء، والبعوض أو من السم من الثعابين مع تحديد معين من الهدف 24-27. هذه الأمثلة تدل على براعة نموذج كلوريد الحديديك. في هذه المقالة، ونحن نركز على طريقتين ودراسة كلوريد الحديديك التي يسببها تجلط الدم على اثنين من نوع سفينة مختلفة. سفينة المساريقي والشريان السباتي.

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	<tbody>
		<tr>
			<td>Whatman chromatography paper</td>
			<td>GE Healthcare</td>
			<td>3030917</td>
			<td></td>
		</tr>
		<tr>
			<td>Iron (III) chloride 40 % (w/v)</td>
			<td>VWR</td>
			<td>24212.298</td>
			<td></td>
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		<tr>
			<td>Rhodamine 6G</td>
			<td>Sigma</td>
			<td>R4127</td>
			<td></td>
		</tr>
		<tr>
			<td>Inverted microscope&#160;</td>
			<td>Olympus</td>
			<td>IX81</td>
			<td></td>
		</tr>
		<tr>
			<td>Digital black-and-white camera&#160;</td>
			<td>Olympus</td>
			<td>XM10</td>
			<td></td>
		</tr>
		<tr>
			<td>Doppler flowmeter</td>
			<td>Transonic</td>
			<td>TS420</td>
			<td></td>
		</tr>
		<tr>
			<td>Nano-doppler flow probe</td>
			<td>Transonic</td>
			<td>0.5 PBS</td>
			<td></td>
		</tr>
		<tr>
			<td>Ketamine</td>
			<td>Hospira&#160;</td>
			<td>0409-2051-05</td>
			<td></td>
		</tr>
		<tr>
			<td>Xylazine (Rampun)</td>
			<td>Bayer</td>
			<td>75313&#160;</td>
			<td></td>
		</tr>
		<tr>
			<td>Petri dish</td>
			<td>Sarstedt</td>
			<td>82.1472</td>
			<td></td>
		</tr>
		<tr>
			<td>Insulin syringe (29 G)</td>
			<td>BD Ultra-Fine</td>
			<td>326103</td>
			<td></td>
		</tr>
		<tr>
			<td>Cotton tipped applicators</td>
			<td>BSN medical</td>
			<td>211827A</td>
			<td></td>
		</tr>
		<tr>
			<td>Dynek dysilk sutures</td>
			<td>Dynek Pty Ltd</td>
			<td>CS30100</td>
			<td></td>
		</tr>
		<tr>
			<td>Dulbecco&#39;s phosphate buffer saline (PBS)</td>
			<td>Gibco life technologies</td>
			<td>21600-069</td>
			<td></td>
		</tr>
		<tr>
			<td>Heating pad</td>
			<td>Kirchner</td>
			<td>T60</td>
			<td></td>
		</tr>
	</tbody>
</table>

ferric chloride-induced thrombosis mouse model on carotid artery and mesentery vessel

Severe thrombosis and its ischemic consequences such as myocardial infarction, pulmonary embolism and stroke are major worldwide health issues. The ferric chloride injury is now a well-established technique to rapidly and accurately induce the formation of thrombi in exposed veins or artery of small and large diameter. This model has played a key role in the study of the pathophysiology of thrombosis, in the discovery and validation of novel antithrombotic drugs and in the understanding of the mechanism of action of these new agents. Here, the implementation of this technique on a mesenteric vessel and carotid artery in mice is presented. The method describes how to label circulating leukocytes and platelets with a fluorescent dye and to observe, by intravital microscopy on the exposed mesentery, their accumulation at the injured vessel wall which leads to the formation of a thrombus. On the carotid artery, the occlusion caused by the clot formation is measured by monitoring the blood flow with a Doppler probe.

والفلورسنت المراقبة intravital المجهري للمساريق سوف تكشف عن تراكم رودامين 6G وصفت الصفائح الدموية وكريات الدم البيضاء على طول جدار الوعاء الدموي أصيب FeCl 3. ويتم رصد تشكيل التدريجي لخثرة جزئية في وعاء مساريق 200 ميكرون (الشكل 1). A خثرة يظهر ببطء وبشكل واضح التع?...

Watch this Scientific Journal Video about Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel at JoVE.com

Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel

The FeCl3 induced thrombosis model in mice is described herein. A method to monitor thrombus growth by intravital microscopy observation on a mesenteric vessel and by blood flow measurement in the carotid artery is presented.

الحديديك تخثر نموذج الفأر على الشريان السباتي ومساريق السفينة التي يسببها كلوريد

Severe thrombosis and its ischemic consequences such as myocardial infarction, pulmonary embolism and stroke are major worldwide health issues. The ferric ...

ferric-chloride-induced-thrombosis-mouse-model-on-carotid-artery

Research

JoVE Journal

Medicine

A Model of Disturbed Flow-Induced Atherosclerosis in Mouse Carotid Artery by Partial Ligation and a Simple Method of RNA Isolation from Carotid Endothelium

Despite the well-known close association, direct evidence linking disturbed flow to atherogenesis has been lacking. We have recently used a modified version of carotid partial ligation methods [1,2] to show that it acutely induces low and oscillatory flow conditions, two key characteristics of disturbed flow, in the mouse common carotid artery. Using this model, we have provided direct evidence that disturbed flow indeed leads to rapid and robust atherosclerosis development in Apolipoprotein E knockout mouse [3]. We also developed a method of endothelial RNA preparation with high purity from the mouse carotid intima [3]. Using this mouse model and method, we found that partial ligation causes endothelial dysfunction in a week, followed by robust and rapid atheroma formation in two weeks in a hyperlipidemic mouse model along with features of complex lesion formation such as intraplaque neovascularization by four weeks. This rapid in vivo model and the endothelial RNA preparation method could be used to determine molecular mechanisms underlying flow-dependent regulation of vascular biology and diseases. Also, it could be used to test various therapeutic interventions targeting endothelial dysfunction and atherosclerosis in considerably reduced study duration.

This describes a partial carotid ligation surgery, which causes disturbed flow conditions and subsequent atherosclerosis development (in two weeks) with intraplaque neo-vascularization (in four weeks) in the mouse common carotid artery. We also describe a novel method of RNA isolation from the carotid intima, providing high purity endothelial RNA.

نموذج من تصلب الشرايين الناتج عن تدفق ديستيربد في الشريان السباتي الماوس بواسطة الربط الجزئي وطريقة بسيطة لعزل الحمض النووي الريبي من بطانة الشريان السباتي

Despite the well-known close association, direct evidence linking disturbed flow to atherogenesis has been lacking. We have recently used a modified ...

Mouse Complete Stasis Model of Inferior Vena Cava Thrombosis

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). In the United States (U.S.), the high morbidity and mortality rates make VTE a serious health concern 1-2. After heart disease and stroke, VTE is the third most common vascular disease 3. In the U.S. alone, there is an estimated 900,000 people affected each year, with 300,000 deaths occurring annually 3. A reliable in vivo animal model to study the mechanisms of this disease is necessary.
The advantages of using the mouse complete stasis model of inferior vena cava thrombosis are several. The mouse model allows for the administration of very small volumes of limited availability test agents, reducing costs dramatically. Most promising is the potential for mice with gene knockouts that allow specific inflammatory and coagulation factor functions to be delineated. Current molecular assays allow for the quantitation of vein wall, thrombus, whole blood, and plasma for assays. However, a major concern involving this model is the operative size constraints and the friability of the vessels. Also, due to the small IVC sample weight (mean 0.005 grams) it is necessary to increase animal numbers for accurate statistical analysis for tissue, thrombus, and blood assays such as real-time polymerase chain reaction (RT-PCR), western blot, enzyme-linked immunosorbent (ELISA), zymography, vein wall and thrombus cellular analysis, and whole blood and plasma assays 4-8.
The major disadvantage with the stasis model is that the lack of blood flow inhibits the maximal effect of administered systemic therapeutic agents on the thrombus and vein wall.

The mouse complete stasis model of inferior vena cava thrombosis yields quantifiable amounts of vein wall tissue and thrombus. It has proven useful for evaluating interactions between the vein wall and the occlusive thrombus and in assessing the progression from acute to chronic inflammation.

الفأرة النموذجي ركود كاملة من الوريد الأجوف السفلي التخثر

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE).  In the United States (U.S.), the high morbidity and ...

Mouse Model of Middle Cerebral Artery Occlusion

Stroke is the most common fatal neurological disease in the United States 1. The majority of strokes (88%) result from blockage of blood vessels in the brain (ischemic stroke) 2. Since most ischemic strokes (~80%) occur in the territory of middle cerebral artery (MCA) 3, many animal stroke models that have been developed have focused on this artery. The intraluminal monofilament model of middle cerebral artery occlusion (MCAO) involves the insertion of a surgical filament into the external carotid artery and threading it forward into the internal carotid artery (ICA) until the tip occludes the origin of the MCA, resulting in a cessation of blood flow and subsequent brain infarction in the MCA territory 4. The technique can be used to model permanent or transient occlusion 5. If the suture is removed after a certain interval (30 min, 1 h, or 2 h), reperfusion is achieved (transient MCAO); if the filament is left in place (24 h) the procedure is suitable as a model of permanent MCAO. This technique does not require craniectomy, a neurosurgical procedure to remove a portion of skull, which may affect intracranial pressure and temperature 6. It has become the most frequently used method to mimic permanent and transient focal cerebral ischemia in rats and mice 7,8. To evaluate the extent of cerebral infarction, we stain brain slices with 2,3,5-triphenyltetrazolium chloride (TTC) to identify ischemic brain tissue 9. In this video, we demonstrate the MCAO method and the determination of infarct size by TTC staining.

We demonstrate in the video a method for producing a middle cerebral artery occlusion in adult mice using an intraluminal monofilament. We also show how to evaluate the extent of cerebral infarction by 2,3,5-triphenyltetrazolium chloride (TTC) staining.

نموذج الفأر من انسداد الشريان الدماغي الأوسط

Stroke is the most common fatal neurological disease in the United States 1. The majority of strokes (88%) result from blockage of blood vessels in the ...

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings.

A model of stent implantation in mouse carotid artery is described. Compared to other similar methods, this procedure is very rapid, simple and accessible, offering the possibility to study in a convenient way the vascular wall reaction to different drug-eluting stents and the molecular mechanisms of restenosis.

نموذج الفئران من زرع دعامات في الشريان السباتي لدراسة عودة التضيق

Despite  the considerable progress made in the stent development in the last decades,  cardiovascular diseases remain the main cause of death in western ...

Adult Mouse Venous Hypertension Model: Common Carotid Artery to External Jugular Vein Anastomosis.

The understanding of the pathophysiology of brain arteriovenous malformations and arteriovenous fistulas has improved thanks to animal models. A rat model creating an artificial fistula between the common carotid artery (CCA) and the external jugular vein (EJV) has been widely described and proved technically feasible. This construct provokes a consistent cerebral venous hypertension (CVH), and therefore has helped studying the contribution of venous hypertension to formation, clinical symptoms, and prognosis of brain AVMs and dural AVFs. Equivalent mice models have been only scarcely described and have shown trouble with stenosis of the fistula. An established murine model would allow the study of not only pathophysiology but also potential genetic therapies for these cerebrovascular diseases.
We present a model of arteriovenous fistula that produces a durable intracranial venous hypertension in the mouse. Microsurgical anastomosis of the murine CCA and EJV can be difficult due to diminutive anatomy and frequently result in a non-patent fistula. In this step-by-step protocol we address all the important challenges encountered during this procedure. Avoiding excessive retraction of the vein during the exposure, using 11-0 sutures instead of 10-0, and making a carefully planned end-to-side anastomosis are some of the critical steps. Although this method requires advanced microsurgical skills and a longer learning curve that the equivalent in the rat, it can be consistently developed.
This novel model has been designed to integrate transgenic mouse techniques with a previously well-established experimental system that has proved useful to study brain AVMs and dural AVFs. By opening the possibility of using transgenic mice, a broader spectrum of valid models can be achieved and genetic treatments can also be tested. The experimental construct could also be further adapted to the study of other cerebrovascular diseases related with venous hypertension such as migraine, transient global amnesia, transient monocular blindness, etc.

We describe a method for creating a reliable model of cerebral venous hypertension in the adult mouse. This model has been widely described and tested in the rat. This new counterpart in the mice opens the possibility of using genetic modified animals and thereby broadens the applications of the model.

الكبار ماوس وريدي ارتفاع ضغط الدم نموذج: الشريان السباتي المشترك لجهات خارجية الوداجي الوريد التحام.

The understanding of the pathophysiology of brain arteriovenous malformations and arteriovenous fistulas has improved thanks to animal models. A rat model ...

Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery

The carotid artery balloon injury model in rats has been well established for over two decades. It remains an important method to study the molecular and cellular mechanisms involved in vascular smooth muscle dedifferentiation, neointima formation and vascular remodeling. Male Sprague-Dawley rats are the most frequently employed animals for this model. Female rats are not preferred as female hormones are protective against vascular diseases and thus introduce a variation into this procedure. The left carotid is typically injured with the right carotid serving as a negative control. Left carotid injury is caused by the inflated balloon that denudes the endothelium and distends the vessel wall. Following injury, potential therapeutic strategies such as the use of pharmacological compounds and either gene or shRNA transfer can be evaluated. Typically for gene or shRNA transfer, the injured section of the vessel lumen is locally transduced for 30 min with viral particles encoding either a protein or shRNA for delivery and expression in the injured vessel wall. Neointimal thickening representing proliferative vascular smooth muscle cells usually peaks at 2 weeks after injury. Vessels are mostly harvested at this time point for cellular and molecular analysis of cell signaling pathways as well as gene and protein expression. Vessels can also be harvested at earlier time points to determine the onset of expression and/or activation of a specific protein or pathway, depending on the experimental aims intended. Vessels can be characterized and evaluated using histological staining, immunohistochemistry, protein/mRNA assays, and activity assays. The intact right carotid artery from the same animal is an ideal internal control. Injury-induced changes in molecular and cellular parameters can be evaluated by comparing the injured artery to the internal right control artery. Likewise, therapeutic modalities can be evaluated by comparing the injured and treated artery to the control injured only artery.

This protocol uses a balloon catheter to cause an intraluminal injury on the rat carotid artery and henceforth elicit neointimal hyperplasia. This is a well-established model for studying the mechanisms of vascular remodeling in response to injury. It is also widely used to determine the validity of potential therapeutic approaches.

إصابة الأوعية الدموية بالون والإدارة داخل اللمعة في الجرذ الشريان السباتي

The carotid artery balloon injury model in rats has been well established for over two decades. It remains an important method to study the molecular and ...

A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is also a valuable model system to test, and to evaluate therapeutics and drugs that negate maladaptive remodeling in the vessel. The injury, or barotrauma, in the vessel lumen caused by an inflated balloon via an inserted catheter induces subsequent neointimal growth, often leading to hyperplasia or thickening of the vessel wall that narrows, or obstructs the lumen. The method described here is sufficiently sensitive, and the results can be obtained in relatively short time (2 weeks after the surgery). The efficacy of the drug or therapeutic against the induced-remodeling can be evaluated either by the post-mortem pathological and histomorphological analysis, or by ultrasound sonography in live animals. In addition, this model system has also been used to determine the therapeutic window or the time course of the administered drug. These studies can leadto the development of a better administrative strategy and a better therapeutic outcome. The procedure described here provides a tool for translational studies that bring drug and therapeutic candidates from bench research to clinical applications.

The rat carotid balloon injury model described below allows researchers to evaluate drugs or therapeutics that negate injury-induced arterial hyperplasia. Detailed pre-surgical preparation, surgical procedure, and post-surgical cares of the animal are described.

بالون إصابة الفئران السباتي نموذج لاختبار التداوي إعادة عرض لمكافحة الأوعية الدموية

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is ...

Ferric Chloride-induced Murine Thrombosis Models

Arterial thrombosis (blood clot) is a common complication of many systemic diseases associated with chronic inflammation, including atherosclerosis, diabetes, obesity, cancer and chronic autoimmune rheumatologic disorders. Thrombi are the cause of most heart attacks, strokes and extremity loss, making thrombosis an extremely important public health problem. Since these thrombi stem from inappropriate platelet activation and subsequent coagulation, targeting these systems therapeutically has important clinical significance for developing safer treatments. Due to the complexities of the hemostatic system, in vitro experiments cannot replicate the blood-to-vessel wall interactions; therefore, in vivo studies are critical to understand pathological mechanisms of thrombus formation. To this end, various thrombosis models have been developed in mice. Among them, ferric chloride (FeCl3) induced vascular injury is a widely used model of occlusive thrombosis that reports platelet activation and aggregation in the context of an aseptic closed vascular system. This model is based on redox-induced endothelial cell injury, which is simple and sensitive to both anticoagulant and anti-platelets drugs. The time required for the development of a thrombus that occludes blood flow gives a quantitative measure of vascular injury, platelet activation and aggregation that is relevant to thrombotic diseases. We have significantly refined this FeCl3-induced vascular thrombosis model, which makes the data highly reproducible with minimal variation. Here we describe the model and present representative data from several experimental set-ups that demonstrate the utility of this model in thrombosis research.

We report a refined procedure of the ferric chloride (FeCl3)-induced thrombosis models on carotid and mesenteric artery as well as vein, characterized efficiently using intravital microscopy to monitor time to occlusive thrombi formation.

الحديديك كلوريد الناجم عن الفئران التخثر نماذج

Arterial thrombosis (blood clot) is a common complication of many systemic diseases associated with chronic inflammation, including atherosclerosis, ...

Phase Contrast Magnetic Resonance Imaging in the Rat Common Carotid Artery

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous studies have shown that abnormal blood flow may be associated with systemic vascular risk. Thus, PC-MRI can facilitate the translation of data obtained from animal models of cardiovascular diseases to pertinent clinical investigations. In this report, we describe the procedure for measuring blood flow in the common carotid artery (CCA) of rats using cine-gated PC-MRI and discuss relevant analysis methods. This procedure can be performed in a live, anesthetized animal and does not require euthanasia after the procedure. The proposed scanning parameters yield repeatable measurements for blood flow, indicating excellent reproducibility of the results. The PC-MRI procedure described in this article can be used for pharmacological testing, pathophysiological assessment, and cerebral hemodynamics evaluation.

The overall goal of this procedure is to measure the blood flow in the rat common carotid artery by using noninvasive phase contrast magnetic resonance imaging.

مرحلة التباين صور الرنين المغناطيسي في الشريان السباتي المشترك الفئران

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous ...

Ferric Chloride-induced Canine Carotid Artery Thrombosis: A Large Animal Model of Vascular Injury

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, we have translated a vascular injury model from a small animal into a large animal (canine), with slight modifications that can be used for pre-clinical screening of prophylactic and thrombolytic agents. In addition to the surgical methods, the modified protocol describes the step-by-step methods to assess carotid artery canalization by angiography, detailed instructions to process both the brain and carotid artery for histological analysis to verify carotid canalization and cerebral hemorrhage, and specific parameters to complete an assessment of downstream thromboembolic events by utilizing magnetic resonance imaging (MRI). In addition, specific procedural changes from the previously well-established small animal model necessary to translate into a large animal (canine) vascular injury are discussed.

Here, we present the modifications necessary to a well characterized and commonly used small animal ferric chloride-induced (FeCl3) carotid artery injury model for use in a large animal vascular injury model. The resulting model can be utilized for pre-clinical trial assessment of both prophylactic and thrombolytic pharmacological and mechanical interventions.

تجلط الشريان السباتي الكلاب المستحثة بكلوريد الحديد: نموذج حيوان كبيرة لإصابة الأوعية الدموية

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, ...