Name: ferric chloride-induced murine thrombosis models
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Description: Watch this Scientific Journal Video about Ferric Chloride-induced Murine Thrombosis Models at JoVE.com

This work was supported by the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health under award numbers R01 HL121212 (PI: Sen Gupta), R01 HL129179 (PI: Sen Gupta, Co-I: Li) and R01 HL098217 (PI: Nieman). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Alle Verfahren und Manipulationen der Tiere wurden von Institutional Animal Care und Verwenden Komitees (IACUC) von der Cleveland Clinic in Übereinstimmung mit den Vereinigten Staaten Public Health Service - Politik auf der Humane Pflege und Verwendung von Tieren, und der NIH Leitfaden für die Pflege genehmigt und Verwendung von Labortieren. 1. Vorbereitungen: <ol><li> Fluoreszenzfarbstoff für Labeling Platelets <ol><li> Bereiten Rhodamin 6G-Lösung, 0,5 mg / ml, ...

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Das FeCl 3 -induzierten Modell ist eines der am häufigsten verwendeten Thrombosemodelle, die nicht nur wertvolle Informationen über genetische Veränderungen auf die Thrombozytenfunktion und Thrombose 7,8,16,19,31-33 liefern kann, kann aber auch ein wertvolles Werkzeug, zur Bewertung der therapeutischen Verbindungen und Strategien zur Behandlung und Prävention von Krankheiten atherothrombotic 11,17,34-37. Hier haben wir unsere Modifikationen und Verfeinerungen dieses Modells gezeigt u...

Arterielle Thrombose (Blutgerinnsel) ist eine häufige Komplikation vieler systemischen mit chronischer Entzündung assoziierte Erkrankungen, einschließlich Atherosklerose, Diabetes, Fettleibigkeit, Krebs und chronische Autoimmun rheumatologischen Erkrankungen. Thromben, die in den arteriellen Kreislauf stammen aus unangemessenen Thrombozytenaktivierung, Aggregation und anschließende gerinnungsMechanismen auftreten, und sind in Herzinfarkt, Schlaganfall und Extremitätenverlust verwickelt. Die Behälterwand ist ein komplexes System , das mehrere Zelltypen einschließt und durch eine Vielzahl von äußeren Faktoren ab, einschließlich Scherspannung, zirkulierenden Blutzellen, Hormonen und Cytokinen, sowie die Expression von Antioxidationsmittel - Proteine ​​in der Gefäßwand. In vitro Experimente replizieren kann nicht beeinflusst dieser komplexen Umgebung und deshalb in - vivo - Studien an Tiermodellen sind entscheidend besseres Verständnis der Mechanismen bei thrombotischer Erkrankungen beteiligt zu ermöglichen. Die Mäuse wurden sim gezeigt zu haben,Ilar Mechanismen für den Menschen im Hinblick auf die Thrombose, Arteriosklerose, Entzündungen und Diabetes 1,2. Weiterhin transgenen und Knockout-Mäuse können die Funktion von spezifischen Genprodukten in einer komplexen physiologischen oder pathologischen Umgebung zu testen erstellt werden. Solche Studien der menschlichen Pathologie nachahmen und bei der Charakterisierung von Arzneimittelwirkungen auf Thrombose wichtige Details bereitstellt, als auch, um Entdeckung neuer Wege und Therapien in Verbindung stehen wichtige mechanistische Informationen zur Verfügung stellen kann. Pathologische arterielle Thromben entstehen durch Schicht Verletzung oder Dysfunktion und Exposition des Blutstroms in die subendothelialen Matrix 3,4 an Endothelzellen. Verschiedene Thrombose Modelle wurden diese Endotheleinrisses zu induzieren entwickelt, wie mechanische Verletzungen, photo Verbindung Rose Bengal-basierte oxidative Schädigung und Laser-Verletzung 5. In diesem Spektrum, Eisenchlorid (FeCl 3) -induzierten Gefäßverletzung ein weit verbreitetes Modell der Thrombose ist. Dieses Reagenz, wennaufgetragen auf die äußere Aspekt der Gefäße induziert , auf vaskulären Zellen oxidativer Schädigung 6-8, mit dem Verlust der endothelialen Zellschutz von Thrombozyten und Komponenten der Gerinnungskaskade zirkuliert. Die FeCl 3 Modell ist einfach und empfindlich auf beiden Antikoagulans und Anti-Thrombozyten Drogen, und hat auf carotis und Oberschenkelarterien, Jugularvenen und mesenterialen und cremasterica Arteriolen und Venolen bei Mäusen, Ratten, Meerschweinchen und Kaninchen 6-15 durchgeführt worden ist . Ein messbarer Parameter in diesem Modell ist die verstrichene Zeit von der Verletzung Gefäßverschluss zu vervollständigen, gemessen als Blutfluss Aufhören mit einem Doppler - Durchflussmesser oder unter direkter Beobachtung mit Intravitalmikroskopie 6,7,9. Eine Reihe von Zeiten zwischen 5 bis 30 min wurde in verschiedenen Studien in C57Bl6 Mäusen 7-10,16, berichtet darauf hindeutet , dass FeCl 3 Konzentrationen, die Art der Anästhesie, OP - Techniken, Maus Alter, genomischen Hintergrund, Verfahren b Messunglood Fluss und andere Umgebungsvariablen haben erhebliche Auswirkungen in diesem Modell. Diese große Variabilität macht es schwierig, Studien von verschiedenen Forschungsgruppen zu vergleichen und kann Erkennung von subtilen Unterschiede erschweren. Mit einer Vision solche Variabilitäten zu minimieren und eine gleichmäßig reproduzierbare in vivo Modellsystem etablieren, haben wir die FeCl 3 -induzierten Arteria carotis Modell verfeinert, die die Daten in hohem Maße reproduzierbar mit minimaler Variation macht 6-10,16-19. In diesem Papier beschreiben wir, und die Fähigkeiten teilen und mehrere repräsentative experimentelle Beispiele berichten, die von diesem Modell profitieren können.

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			<td height="20" style="height:20px;width:351px;">Surgical Scissors - Tungsten Carbide</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td style="width:119px;">14502-14</td>
			<td style="width:325px;">cut and hold skin</td>
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			<td height="20" style="height:20px;width:351px;">Micro-Adson Forceps - Serrated/Straight/12cm</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td>11018-12</td>
			<td>cut and hold skin</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:351px;">Metzenbaum Fino Scissors - Tungsten Carbide/Curved/Blunt-Blunt/14.5cm</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td style="width:119px;">14519-14&#160;&#160;</td>
			<td>to dissect and separate soft tissue</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:351px;">Ultra Fine Hemostat - Smooth/Curved/12.5cm</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td>13021-12</td>
			<td>to dissect and separate soft tissue</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Graefe Forceps - Serrated/Straight/10cm</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td style="width:119px;">11050-10</td>
			<td>to dissect and separate soft tissue</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:351px;">Dumont #5 Fine Forceps - Biology Tips/Straight/Inox/11cm</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td>11254-20&#160;</td>
			<td>Isolate vessel from surounding tissue</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:351px;">Dumont #5XL Forceps - Standard Tips/Straight/Inox/15cm</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td>11253-10</td>
			<td>Isolate vessel from surounding tissue</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:351px;">Blunt Hook- 12cm/0.3mm Tip Diameter</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td>10062-12</td>
			<td>Isolate vessel from surounding tissue</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:351px;">Castroviejo Micro Needle Holders</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td>12061-02</td>
			<td>Needle holders</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:351px;">Suture Thread 4-0</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td>18020-40</td>
			<td>For fix the incisors to the plate</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:351px;">Suture Thread 6-0</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td>18020-60</td>
			<td>For all surgery and ligation</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:351px;">Kalt Suture Needles</td>
			<td style="width:159px;">Fine Science Tools&#160;</td>
			<td>12050-03</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">rhodamine 6G&#160;</td>
			<td style="width:159px;">Sigma</td>
			<td>83697-1G</td>
			<td>To lebel platelets</td>
		</tr>
		<tr height="26">
			<td height="26" style="height:26px;">FeCl3 (Anhydrous)</td>
			<td style="width:159px;">Sigma</td>
			<td style="width:119px;">12321</td>
			<td>To induce vessel injury</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Papaverine hydrochloride</td>
			<td style="width:159px;">Sigma</td>
			<td>P3510</td>
			<td>To inhibit gut peristalsis.</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:351px;">Medline Surgical Instrument Sterilization Steam Autoclave Tapes</td>
			<td style="width:159px;">Medline</td>
			<td>111625</td>
			<td>To fix the mouse to the plate</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:351px;">Fisherbrand&#8482;&#160;Syringe Filters - Sterile 0.22&#181;m</td>
			<td style="width:159px;">Fisher</td>
			<td>09-720-004</td>
			<td>For sterlization of solutions injected to mice</td>
		</tr>
		<tr height="26">
			<td height="26" style="height:26px;width:351px;">Fisherbrand&#8482;&#160;Syringe Filters - Sterile 0.45&#181;m</td>
			<td style="width:159px;">Fisher</td>
			<td>09-719D</td>
			<td>To filter the FeCl3 solution</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:351px;">Sterile Alcohol Prep Pad</td>
			<td style="width:159px;">Fisher</td>
			<td>06-669-62</td>
			<td>To sterilize the surgical site</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:351px;">Agarose&#160;</td>
			<td style="width:159px;">BioExpress</td>
			<td>E-3120-500</td>
			<td>To make gel stage</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:351px;">Leica DMLFS fluorescent microscope</td>
			<td style="width:159px;">Leica</td>
			<td style="width:119px;"></td>
			<td>Intravital microscope</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:351px;">GIBRALTAR Platform and X-Y Stage System</td>
			<td style="width:159px;">npi electronic GmbH</td>
			<td style="width:119px;"></td>
			<td style="width:325px;">http://www.npielectronic.de/products/micropositioners/burleigh/gibraltar.html</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:351px;">Streampix version 3.17.2 software</td>
			<td style="width:159px;">NorPix</td>
			<td style="width:119px;"></td>
			<td>https://www.norpix.com/</td>
		</tr>
	</tbody>
</table>

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.

Arteria carotis Thrombosis Modell Bei Mäusen mit C57BL6 Hintergrund empfehlen wir die Verwendung von 7,5% FeCl 3 Behälter für 1 min als Ausgangspunkt zu behandeln. Unter der Behandlung von 7,5% FeCl 3, Grenzen des verletzten Bereich und normalen Gefäßwand werden unter dem Mikroskop (siehe Online - Video - 1) leicht identifiziert, was darauf hindeutet , dass die endotheliale Schicht erheb...

Watch this Scientific Journal Video about Ferric Chloride-induced Murine Thrombosis Models at JoVE.com

Ferric Chloride-induced Murine Thrombosis Models

Wir berichten über ein raffiniertes Verfahren des Eisenchlorid (FeCl 3) induzierte Thrombose - Modelle auf carotis und A. mesenterica sowie Vene, dadurch effizient Intravitalmikroskopie unter Verwendung von Zeit zu überwachen Thrombenbildung zu okklusiv.

Ferric Chloride-induzierte Murine Thrombosis Models

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

Research

JoVE Journal

Medicine

Electrolytic Inferior Vena Cava Model (EIM) of Venous Thrombosis

Electrolytic Inferior Vena Cava Model EIM of Venous Thrombosis

Elektrolytische Inferior Vena Cava Model (EIM) von Venenthrombosen

Animal models serve a vital role in deep venous thrombosis (DVT) research in order to study thrombus formation, thrombus resolution and to test potential ...

Forschung

Medizin

Mouse Complete Stasis Model of Inferior Vena Cava Thrombosis

Maus Komplette Stasis Model of Inferior Vena Cava Thrombose

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

Segmentation and Measurement of Fat Volumes in Murine Obesity Models Using X-ray Computed Tomography

Segmentierung und Messung von FAT-Volumes in Murine Obesity Modellen mithilfe von Röntgen-Computertomographie

Obesity is associated with increased morbidity and mortality as well as reduced metrics in quality of life.1 Both environmental and genetic factors are ...

Quantitative Analysis and Characterization of Atherosclerotic Lesions in the Murine Aortic Sinus

Atherosclerosis is a disease of the large arteries and a major underlying cause of myocardial infarction and stroke. Several different mouse models have ...

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

Intrastriataler Injektion von Eigenblut oder Clostridien-Kollagenase als Murine Modelle der Hirnblutung

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

Orthotopic Injection of Breast Cancer Cells into the Mammary Fat Pad of Mice to Study Tumor Growth.

Orthotopische Injektion von Brustkrebszellen in das Brustfettpolster von Mäusen, das Tumorwachstum zu studieren.

Breast cancer growth can be studied in mice using a plethora of models. Genetic manipulation of breast cancer cells may provide insights into the ...

Adapting Human Videofluoroscopic Swallow Study Methods to Detect and Characterize Dysphagia in Murine Disease Models

Anpassung Menschen Videofluoroscopic Swallow Studienmethoden nachgewiesen und charakterisiert Dysphagie in Murine Krankheitsmodelle

This study adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating ...

High-frequency Ultrasound Imaging of Mouse Cervical Lymph Nodes

Hochfrequenz-Ultraschall-Bildgebung der Maus Halslymphknoten

High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal ...

A Multicenter MRI Protocol for the Evaluation and Quantification of Deep Vein Thrombosis

Eine multizentrische MRI-Protokoll für die Beurteilung und Quantifizierung von tiefen Venenthrombosen

We evaluated a magnetic resonance venography (MRV) approach with gadofosveset to quantify total thrombus volume changes as the principal criterion for ...

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

Eisenchlorid-induzierte Thrombose Mausmodell für Halsschlagader und Mesentery Vessel

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