The work was supported by the intramural research program of the NIH, National Institute on Aging, and by a Priority Research Centers Program grant from the National Research Foundation (NRF-2009-0093812) funded by the Ministry of Science, Information and Communication Technology, &amp; Future Planning, the Republic of Korea (H.T.). We thank Dr. Han-sol Park for putting "material" part together for the manuscript.

NOT: sıçan balon yaralanması modelinde ve rekombinant sRAGE ve ultrason ultrason çalışmaların enjeksiyonu da dahil olmak üzere ilgili prosedürlerin kullanılması Ulusal Yaşlanma Enstitüsü Hayvan Bakım ve Kullanım Komitesi (ACUC), NIH tarafından onaylanmıştır. 1. Ön cerrahi Hazırlıklar <ol><li> Enstrüman, Cerrahi Platformu ve Kişisel Koruma Ekipmanı. <ol><li> Bu prosedürde kullanılan tüm cerrahi aletler ve reaktifler için malzeme ve ekipman en Tabloya bakınız. cerrahi işlem öncesi tüm cerrahi aletler otoklav. NOT: Aynı gün yapılan birden fazla ameliyatlar için, ameliyatlar arasında aletleri sterilize etmek için önceden ısıtılmış cam boncuk sterilizatör kullanın. </li><li> % 70 alkol ile işletim platformu yüzeyini sterilize edin. cerrahi önlük, saç kapağı, cerrahi maske, koruyucu gözlük ve eldiven giyin. Ek bizim için cerrahi bir platform yakın sterilize eldiven bir kutu bırakıne. </li></ol></li><li> Balon Kateter hazırlanması. <ol><li> steril su ile 1 ml şırınga doldurun ve steril suyla doldurulmuş iki yollu şırınga ekleyin. Yavaşça balon kateterin Luer-lock kısmını doldurmak ve kateterin açılması hava kabarcıklarını çıkarmak için musluk suyu ile itin. </li><li> balon sağlamak için Test balon şişirme su 0,02 ml ile şişirilir edilebilir. kurutma ve kirlenmeyi önlemek için ameliyattan önce steril suda bir kap içinde bir balon ucu saklayın. </li></ol></li><li> Anestezi ve Hayvan hazırlanması. <ol><li> erkek Wistar sıçanlar tartılır (400-450 gr) ve kimliği teyit etmek için kulak küpesi kontrol edin. Böyle ayak veya kuyruk kıstırma olarak pedal çekme refleksi kontrol ederek sedasyon derinliğini kontrol edin, sonra indüksiyon odasında sıçan yerleştirin buharlaştırıcı açmak ve 3.5-4.0% izofluran düzeyini ve 1.5-2.0 L. oksijen seviyesini ayarlamak hayvan. </li><li> (Anestezi ulaştıktan sonra <em&gt; hayvan) Pedal çekilme refleksi yoksun, yani cerrahi platforma hayvan aktarmak ve bir anestezi buharlaştırıcı bağlanan bir burun konisi ile sıçan kanca. L. Periyodik sıçan tamamen rahat ve hareketsiz olduğundan emin olmak için, hayvanın ayak veya kuyruk kısma sedasyon derinliğini kontrol 0.6-1.0 kadar 1.5-2.0 ve oksijene izofluran konsantrasyonu ayarlayın. </li><li> anestezi cerrahi seviyeye ulaştıktan sonra, sadece hayvan saç kesme ile sternum üzerinde aşağı çeneden ventral boyun bölgesini tıraş ve povidon-iyot ve% 70 etanol 3 kez 1:10 seyreltme dönüşümlü traş cildi çubukla. </li><li> kurumasını önlemek için bir pamuklu çubuk ile hayvanın gözleri açık oftalmik çözüm yerleştirin. operasyon sırasında kurumasını önlemek için içme suyu ile hayvanın dilini ve ağzını ıslatın. </li><li> Steril cerrahi levha ile sıçan Kapak ve boyun bölgesini ortaya çıkarmak için sayfayı kesti. yatar pozisyonda o hayvan yerleştirinna cerrah doğru kafa ile cerrahi platformda pedi ısıtılır. bant kullanarak cerrahi platforma hayvanın uzuvlarını sabitleyin. </li></ol></li></ol> 2. Cerrahi İşlemleri <ol><li> Diseksiyon ve sol karotis İzolasyonu <ol><li> tüm yol sadece göğüs kafesine üzerinde sternum üstüne kuyruk doğru bir yönde çene altına düz bir kesi yapmak için bir neşter kullanın. açık açık kas tabakası açığa çıkarmak için cilt altında tükürük salgı dokuları incelemek için bir 7S forseps kullanabilir. Ayrı kas dokuları karotis damar sistemi ve boyun bölgesinde vagus sinirine erişmek için. </li><li> Açık açık karotis arter çevre dokulara incelemek ve dikkatle vagus siniri ve vasküler fasya zarar görmemesi için ayırın. Sürekli sternum aşağı iç ve dış şube ve karotis arter ortaya çıkarmak için karotid arter bifurkasyonu kadar teşrih. </li></ol></li><li> Arteriot hazırlanmasıomy <ol><li> geri çekme ve hemostaz için, sol karotis arter en yakın yerinde bir bitişik harfleri ve çatallanma konumu hemen distalinde başka bitişik harfleri yerleştirin. </li><li> kafasına doğru arter geri çekmek için mümkün olduğunca bifurkasyonundan eksternal karotid arter bir 4,0 ipek sütür yerleştirin. Kalıcı artan farenks, oksipital ve arteriyel sızıntısı önlemek için üstün tiroid dahil olmak üzere dış karotid arter boyunca 4.0 ipek sütür ile küçük arterleri bağlayabilmesi. </li><li> önemli bir retrograd kan kaybını önlemek için internal karotid arter etrafında bir 4.0 ipek sütür yerleştirin. Genellikle, iç dalının mevcut uzunluğu az. internal karotid arter görselleştirmek için hafifçe sağa üstteki karotis arter geri çekilmeden tarafından mümkün olduğunca internal karotid arter maruz kalmaktadır. </li></ol></li><li> Balon Kateter giriş <ol><li> karotid a proksimal sütür geri çekinrtery ve geçici olarak kan akışını durdurmak için gemide bir arteriyel kelepçe yerleştirin. mümkün olduğunca sütür distal olarak bir yerde dış karotis arter üzerinde kesi küçük (arter çevresinin 1/4 1/3) yapın. </li><li> Yavaşça kesi içine un-şişirilmiş balon kateteri yerleştirin ve sonra karotis arter arteriyel kelepçe yakın lümen içinde kateteri ilerlemek. kelepçe çıkarın ve daha kesi yaklaşık 35-40 mm, aort kemer balon kateteri ilerlemek. </li></ol></li><li> balon Yaralanma <ol><li> Elle bağlı şırınga ile 0.02 ml bir hacme kadar kateter şişirmek ve şırınga ve kateter arasında musluğunu kilidi. Yavaş yavaş rotasyonlar ile kateteri. Kateter arteriotomic kesi yakın olduğunda, balon deflate. özgün konumuna geri kateteri ilerletin. </li><li> Toplam 3 kez 2.4.1 tekrarlayın. Dikkatle arter lümeni gelen kateteri çıkarın. </li></ol></li><li> Cerrahi Yara Close Up <ol><li> dikişlerle arteriyotomi kapatın. kan akışını geri internal karotid arter bırakın. arteriyel kanama veya sızıntı olup olmadığını kontrol edin. Kanama oluşursa, kanamayı durdurmak için biraz basıncı ile gazlı bez parçası uygulayın. </li><li> prosedür için kullanılan sütür ve kelepçeler geri kalanını çıkarın. 6.0 dikişlerle glandüler doku kapatın. cilt sütür veya yara klipleri ile cilt kapatın. izofluran kapatın ve birkaç dakika saf oksijen ile hayvan bırakın. </li></ol></li></ol> Therapeutics 3. İdare, Analjezikler, Post-cerrahi Bakımı ve Ötenazi <ol><li> Therapeutics ve Analjezikler İdaresi. <ol><li> Ameliyatı takiben, (0.03 mg / kg) kas içi buprenorfin enjekte. ameliyatı sırasında kan kaybım telafi etmek için 5 ml önceden ısıtılmış steril tuzlu su deri altına enjekte edilir. periton içine sRAGE (0.5 ng / g) (tedavi edici) enjekte edilir. </li><li> Oph ile tekrar gözler nemlendirinthalmic merhem. ısı yastığı sıçan yerleştirin ve sternum yatma korumak için tam bilinç kavuşur kadar hayvan izleyin. </li><li> temiz yatak ile bir kafesine sıçan dönün ve geri vivari için kafesi getirmek. katılan veteriner ve bakıcıları uyarmak için kafesin özel bir gözlem kartı yerleştirin. </li></ol></li><li> Ameliyat sonrası Temizleme <ol><li> çöp veya özel atık kabına ya iğneler ve ark yastıkları, bezlerden de dahil olmak üzere kullanılan cerrahi malzeme koyun. Ameliyat platformu dezenfekte edin ve cerrahi aletler temizleyin. </li></ol></li><li> Ameliyat sonrası bakım <ol><li> 48 saat ameliyat sonrası dönemde buprenorfin (0.03 mg / kg) günde iki kez (bid) uygulayınız. Böyle hareketsizlik, beslenme yetersizliği, hutched duruş, karıştırdı kürk ve face olarak sıkıntının ortak belirtileri 48 saat ameliyat sonrası dönemde yakından hayvan izleyin. yara kızarıklık koşullarını, şişme, yarılması ve enfeksiyonlar izleyin. NOT:Ek tedaviler veteriner tavsiye katılıyor göre reçete edilebilir. </li><li> veteriner tavsiye katılıyor göre dikiş veya yara klipleri çıkarın. </li></ol></li><li> Ötenazi <ol><li> İki hafta ameliyattan sonra, 22 analizleri otopsi histo-morfolojik için karotis arterler izole etmek sıçan euthanize. % 5-20 izofluran solunum tamamen durması kadar en az 2 dakika süreyle hava doymuş ihtiva eden bir bölme sıçan yerleştirin. Önceki organ ve dokuların diseksiyonu ölüm doğrulayın. </li></ol></li></ol>

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Yazarlar hiçbir rakip mali çıkarları olduğunu beyan ederim.

karotid arter lümeninde duvar endoteli kaldırır yaralanma oluşturmak için balonu şişirmek için kullanılan iki yöntem olmuştur. Bir sıvı 20 ile bağlı şırıngayı doldurmak ve diğer hava basıncı 21 kullanmaktır. Biz tam sıvı hacmi (0.02 ml) her işlem için kullanılacak, çünkü sıvı dolu şırıngayı kullanmayı tercih eder. Bu prosedür uygulanan her bir hayvanın yaralanma benzer bir seviyeye neden balon bir hassas ve tekrarlanabilir enflasyonu oluşturur. şırınga s?...

Anjiyoplasti ateroskleroz gibi patolojik durumlar sonuçtaki daralmış veya tıkalı damarları genişletmek için kullanılan bir endovasküler işlemdir. anjiyoplasti yaygın bir komplikasyon cerrahi yaralanmalar ve sonraki inflamasyon kaynaklı vasküler yeniden nedeniyle oluşur ameliyat sonrası neointimal hiperplazi veya restenoz vardır. Bu koşullar damar düz hücreler ve çoklu patofizyolojik 1-3 çoğalmasına yol açar. Neointimal hiperplazi gemi yeniden kalınlaşır ve ilk yıl içinde% 60 anjiyoplasti sonrası hastalarda kadar oluşur. Bu nedenle, restenoz yaygın olarak kullanılan anjiyoplasti prosedür 4 büyük bir başarısızlık. Uyuşturucu elüsyon stent implantasyonu restenoz engellemeye yardımcı olsa da, yalnızca seçilen adaylar bu pahalı prosedürü 5 uğrayabilir. hayvan ve klinik çalışmalar hem kronik inflamasyon vascu tarafından oluşturulan kurduklar yaralanma ve / veya cerrahi yara anjiyoplasti sonrası neointimal büyüme 2,4 için ana uyarıcı olarak hizmet vermektedir. Bu nedenle sıçan karotis balon yaralanma modeli taklit klinik durum ve vasküler yeniden yapılanma ve vasküler hücre çoğalması 6-9 katıldıklarını hücresel faktörleri belirlemek için değerli bir model sistem olarak hizmet vermektedir. Bu model sistemi, ön-klinik çalışmalarda translasyonel 10-14 neointimal büyümede ilaçlarla tedavi ve tedavi reaktifler için son derece yararlıdır değerlendirmek için bir araç ve / veya ekran. Fare karotis tel yaralanması modelinde 15 ve fare femoral arter tel yaralanması modelinde 16, sıçan karotis balon yaralanma modeli verdirdiler yaralanma tekrarlanabilirlik kolaylaştırır cerrahi prosedür kolaylığı için boyutu yeterince büyük olma avantajları vardır karşılaştırıldığında. Bu addit edecek birincil hücreler daha çok sayıda (örneğin, vasküler düz kas hücreleri, endotelyal hücreler) sağlayabilirional in vitro çalışmalar vasküler remodeling düzenleyen moleküler mekanizmayı tanımlamak için. Önemli olarak, farelere kıyasla, sıçanlar fizyolojik ve toksikolojik çalışmalar 17 için daha iyi bir model olduğu bilinmektedir. Sıçan modeli bir dezavantaj ya da sınırlama genetik modifiye ve gen nakavt modellerinin olmaması olmasına rağmen, bu dezavantaj sıçan genomik dizisinin kullanılabilirliği ve bu tür işler CRISPR-CAS teknolojisi gibi güçlü genomik düzenleme araçları son gelişme ile aşılabilir farklı model sistemlerde 18,19 genomik dizilerin geniş aralıkları mümkün manipülasyon. Sıçan balon yaralanma modeli birden laboratuarları ve çeşitli kapsamlı protokoller tarafından kullanılmasına rağmen 20,21 yayınlanmış, bu protokol öncesi cerrahi hazırlıkları daha fazla ayrıntı vermeyi amaçlamaktadır ve bu cerrahi uygulama kurmak için bu prosedüre yeni araştırmacılara yol açabilir. Biz de t ameliyat sonrası bakım vurgulamakCanlı hayvanların 13,22 değil sadece arteriyel remodeling terapötik etki postmortem patolojik ve histomorfolojik analizler değil, aynı zamanda ultrason sonografik çalışmalar veriyor o hayvanlar.

<table><tbody><tr><td>2 F Fogarty balloon embolectomy catheter&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td>Edwards Lifesciences&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td></td><td></td></tr><tr><td>Standard scalpel</td><td>Fine Science Tools</td><td></td><td></td></tr><tr><td>Small&amp;nbsp; curved forceps (Large radius Dumont#7shanks curved)&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td>Fine Science Tools&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td></td><td></td></tr><tr><td>Large, medium and small micro-scissors</td><td>Roboz</td><td></td><td></td></tr><tr><td>Needles (20 G)&amp;nbsp;&amp;nbsp;</td><td>TycoHealthcare</td><td></td><td></td></tr><tr><td>Micro-surgery forceps with micro-blunted atraumatic tips</td><td>Fine Science Tools&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td></td><td></td></tr><tr><td>Atraumatic straight small arterial clamps&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td>Fine Science Tools&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td></td><td></td></tr><tr><td>Retractor&amp;nbsp; with maximum spread 5.5 cm long blunt teeth</td><td>Fine Science Tools&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td></td><td></td></tr><tr><td>Silk suture (4.0 and&amp;nbsp; 6.0 )</td><td>Fine Science Tools&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td></td><td></td></tr><tr><td>Syringe (1.0 ml)&amp;nbsp;</td><td>BD&amp;nbsp;</td><td></td><td></td></tr><tr><td>Curity gauze sponges</td><td>AllegroMedical</td><td></td><td></td></tr><tr><td>Cotton tip applicators sterile and non-sterile</td><td>Puritan Medical Products</td><td></td><td></td></tr><tr><td>Compact hot bead sterilizer</td><td>Fine Science Tools</td><td></td><td></td></tr><tr><td>Self-regulating heating pad</td><td>Fine Science Tools&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td></td><td></td></tr><tr><td>ADS200 anesthesia system/ventilator</td><td>Paragon Medical</td><td></td><td></td></tr><tr><td>Isoflurane (forane), liquid form</td><td>Baxter</td><td></td><td></td></tr><tr><td>Sodium chloride 0.9% (Saline)&amp;nbsp;</td><td>Hospira</td><td></td><td></td></tr><tr><td>Buprenex (buprenorphine)&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td>Reckitt Benckiser Healthcare (UK) Ltd.&amp;nbsp;</td><td></td><td></td></tr><tr><td>70% alcohol</td><td>Fisher</td><td></td><td></td></tr><tr><td>1:10 Betadine</td><td>Fisher</td><td></td><td></td></tr></tbody></table>

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.

İki hafta balon yaralanma sonrası, sıçan ötenazi ve karotis arterler histo-morfolojik analizler için izole edilmiştir. Hem sol karotis arter ve un sağ işletilen arter işlenmiş, kesit çapraz ve parafine gömülü olduğunu işletilmektedir. parafin numuneleri daha sonra ince kesitli ve hematoksilen-eozin (H &amp; E) ile boyandı vardır. Histo-Şekil incelemesi dijital görüntü analiz sistemi kullanılarak gerçekleştirilir. Arter hasat ve Histo-morfolojik analiz ayrıntıl...

Watch this Scientific Journal Video about A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics at JoVE.com

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

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.

Rat Karotis Balon Yaralanma Modeli Anti-vasküler Tadilat Therapeutics Test

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 ...

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Research

JoVE Journal

Medicine

8.7K Görüntüleme.  National Institute on Aging. 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. 

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

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.

Kısmi ligasyon Fare Karotis Arter Disturbed Akış Kaynaklı Ateroskleroz ve Karotis Endotel RNA İzolasyonu Basit Bir Yöntem Bir Model

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

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Murine Spinotrapezius Model to Assess the Impact of Arteriolar Ligation on Microvascular Function and Remodeling

The murine spinotrapezius is a thin, superficial skeletal support muscle that extends from T3 to L4, and is easily accessible via dorsal skin incision. Its unique anatomy makes the spinotrapezius useful for investigation of ischemic injury and subsequent microvascular remodeling. Here, we demonstrate an arteriolar ligation model in the murine spinotrapezius muscle that was developed by our research team and previously published1-3. For certain vulnerable mouse strains, such as the Balb/c mouse, this ligation surgery reliably creates skeletal muscle ischemia and serves as a platform for investigating therapies that stimulate revascularization. Methods of assessment are also demonstrated, including the use of intravital and confocal microscopy. The spinotrapezius is well suited to such imaging studies due to its accessibility (superficial dorsal anatomy) and relative thinness (60-200 &mu;m). The spinotrapezius muscle can be mounted en face, facilitating imaging of whole-muscle microvascular networks without histological sectioning. We describe the use of intravital microscopy to acquire metrics following a functional vasodilation procedure; specifically, the increase in arterilar diameter as a result of muscle contraction. We also demonstrate the procedures for harvesting and fixing the tissues, a necessary precursor to immunostaining studies and the use of confocal microscopy.

We demonstrate a novel arterial ligation model in murine spinotrapezius muscle, including a step-by-step procedure and description of required instrumentation. We describe the surgery and relevant outcome measurements relating to vascular network remodeling and functional vasodilation using intravital and confocal microscopy.

Mikrovasküler Fonksiyon ve Tadilat üzerine Arteriolar Ligasyonu etkisini değerlendirmek için mürin Spinotrapezius Modeli

The murine spinotrapezius is a thin, superficial skeletal support muscle that extends from T3 to L4, and is easily accessible via dorsal skin incision. ...

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.

Restenoz Çalışmaları Karotis Arter Stent İmplantasyonu bir murin Modeli

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

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.

Sıçan Karotis Arter Vasküler Balon Yaralanma ve intraluminal İdaresi

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 ...

Murine Model of Femoral Artery Wire Injury with Implantation of a Perivascular Drug Delivery Patch

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. While these therapies lead to the rapid restoration of blood flow, these technologies remain limited by restenosis in the case of bare metal stents and angioplasty, or reduced healing and possibly enhanced risk of thrombosis in the case of drug eluting stents. A key pathophysiological mechanism in the formation of restenosis is intimal hyperplasia caused by the activation of vascular smooth muscle cells and inflammation due to arterial stretch and injury. Surgeries that induce arterial injury in genetically modified mice are useful for the mechanistic study of the vascular response to injury but are often technically challenging to perform in mouse models due to the their small size and lack of appropriate sized devices. We describe two approaches for a surgical technique that induces endothelial denudation and arterial stretch in the femoral artery of mice to produce robust neointimal hyperplasia. The first approach creates an arteriotomy in the muscular branch of the femoral artery to obtain vascular access. Following wire injury this arterial branch is ligated to close the arteriotomy. A second approach creates an arteriotomy in the main femoral artery that is later closed through localized cautery. This method allows for vascular access through a larger vessel and, consequently, provides a less technically demanding procedure that can be used in smaller mice. Following either method of arterial injury, a degradable drug delivery patch can be placed over or around the injured artery to deliver therapeutic agents.

We describe a surgical technique that produces wire injury in the femoral artery of mice to induce neointimal hyperplasia to serve as a model testing system for the perivascular delivery of therapeutic compounds for the inhibition of restenosis.

Bir Perivasküler Drug Delivery Patch İmplantasyonunda ile Femoral Arter Tel Yaralanma sıçan Modeli

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. ...

Induction of Accelerated Atherosclerosis in Mice: The "Wire-Injury" Model

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. Moreover, by rupture of the defective vascular wall, atherosclerosis induces occlusive thrombus formation, which represents the main cause of myocardial infarction or stroke and the most frequent cause of death. Despite the advances in the cardiovascular field, many questions remain unanswered, and additional basic research is essential to improve our understanding of the molecular mechanisms during atherosclerosis and its effects. Due to limited clinical studies, there is a need for representative animal models recreating atherosclerotic conditions such as neointima formation after stent implantation, balloon angioplasty, or endarterectomy. Since the mouse presents many advantages and is the most frequently used model for studying molecular processes, the current study proposes an invasive procedure of endothelial denudation, also known as the wire-injury model, which is representative of the human condition of neointima formation in arteries after revascularization procedures.

This study describes an invasive procedure for the induction of accelerated atherosclerosis in mice. In comparison to other methods using electric- or cryo-induced injury, mechanical-induced injury mimics the human condition of restenosis after revascularization therapies and is ideal for the study of the molecular mechanisms involved.

Farelerde Hızlandırılmış Ateroskleroz Indüksiyonu: "Tel-Yaralanma" Modeli

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. ...

Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model

Percutaneous vascular interventions uniformly result in arterial denudation injuries that subsequently lead to thrombosis and restenosis. These complications can be attributed to impairments in re-endothelialization within the wound margins. Yet, the cellular and molecular mechanisms of re-endothelialization remain to be defined. While several animal models to study re-endothelialization after arterial denudation are available, few are performed in the mouse because of surgical limitations. This undermines the opportunity to exploit transgenic mouse lines and investigate the contribution of specific genes to the process of re-endothelialization. Here, we present a step-by-step protocol for creating a highly reproducible murine model of arterial denudation injury in the infrarenal abdominal aorta using external vascular clamping. Immunocytochemical staining of injured aortas for fibrinogen and &#946;-catenin demonstrate the exposure of a pro-thrombotic surface and the border of intact endothelium, respectively. The method presented here has the advantages of speed, excellent overall survival rate, and relative technical ease, creating a uniquely practical tool for imposing arterial denudation injury in transgenic mouse models. Using this method, investigators may elucidate the mechanisms of re-endothelialization under normal or pathological conditions.

Understanding the cellular and molecular mechanisms of re-endothelialization following arterial denudation injury is of paramount importance in preventing thrombosis and restenosis of arteries. Here we describe a protocol for reproducible arterial denudation injury of the infrarenal abdominal aorta. The procedure was developed to investigate the underlying mechanisms that regulate endothelial regeneration using mouse models.

Bir Fare Modelinde İnfrarenal Abdominal Aort Bağlama Ekipmanları tarafından tekrarlanabilir Arter denüdasyon Yaralanma

Percutaneous vascular interventions uniformly result in arterial denudation injuries that subsequently lead to thrombosis and restenosis. These ...

The Rabbit Model of Accelerated Atherosclerosis: A Methodological Perspective of the Iliac Artery Balloon Injury

Acute coronary syndrome resulting from coronary occlusion following atherosclerotic plaque development and rupture is the leading cause of death in the industrialized world. New Zealand White (NZW) rabbits are widely used as an animal model for the study of atherosclerosis. They develop spontaneous lesions when fed with atherogenic diet; however, this requires long time of 4 - 8 months. To further enhance and accelerate atherogenesis, a combination of atherogenic diet and mechanical endothelial injury is often employed. The presented procedure for inducing atherosclerotic plaques in rabbits uses a balloon catheter to disrupt the endothelium in the left iliac artery of NZW rabbits fed with atherogenic diet. Such mechanical damage caused by the balloon catheter induces a chain of inflammatory reactions initiating neointimal lipid accumulation in a time dependent fashion. Atherosclerotic plaque following balloon injury show neointimal thickening with extensive lipid infiltration, high smooth muscle cell content and presence of macrophage derived foam cells. This technique is simple, reproducible and produces plaque of controlled length within the iliac artery. The whole procedure is completed within 20 - 30 min. The procedure is safe with low mortality and also offers high success in obtaining substantial intimal lesions. The procedure of balloon catheter induced arterial injury results in atherosclerosis within two weeks. This model can be used for investigating the disease pathology, diagnostic imaging and to evaluate new therapeutic strategies.

Animal models of atherosclerosis are essential to understand the mechanism and to investigate newer approaches to prevent plaque development or rupture, a leading cause of death in the industrialized world. This protocol uses a combination of balloon injury and cholesterol rich diet to induce atherosclerotic plaques in rabbit iliac artery.

Tavşan modeli hızlandırılmış ateroskleroz: iliyak arter balon yaralanma bir metodolojik açıdan

Acute coronary syndrome resulting from coronary occlusion following atherosclerotic plaque development and rupture is the leading cause of death in the ...

A Rat Carotid Artery Pressure-Controlled Segmental Balloon Injury with Periadventitial Therapeutic Application

Cardiovascular disease remains the leading cause of death and disability worldwide, in part due to atherosclerosis. Atherosclerotic plaque narrows the luminal surface area in arteries thereby reducing adequate blood flow to organs and distal tissues. Clinically, revascularization procedures such as balloon angioplasty with or without stent placement aim to restore blood flow. Although these procedures reestablish blood flow by reducing plaque burden, they damage the vessel wall, which initiates the arterial healing response. The prolonged healing response causes arterial restenosis, or re-narrowing, ultimately limiting the long-term success of these revascularization procedures. Therefore, preclinical animal models are integral for analyzing the pathophysiological mechanisms driving restenosis, and provide the opportunity to test novel therapeutic strategies. Murine models are cheaper and easier to operate on than large animal models. Balloon or wire injury are the two commonly accepted injury modalities used in murine models. Balloon injury models in particular mimic the clinical angioplasty procedure and cause adequate damage to the artery for the development of restenosis. Herein we describe the surgical details for performing and histologically analyzing the modified, pressure-controlled rat carotid artery balloon injury model. Additionally, this protocol highlights how local periadventitial application of therapeutics can be used to inhibit neointimal hyperplasia. Lastly, we present light sheet fluorescence microscopy as a novel approach for imaging and visualizing the arterial injury in three-dimensions.

The rat carotid artery balloon injury mimics the clinical angioplasty procedure performed to restore blood flow in atherosclerotic vessels. This model induces the arterial injury response by distending the arterial wall, and denuding the intimal layer of endothelial cells, ultimately causing remodeling and an intimal hyperplastic response.

Periadventitial Terapötik Uygulama ile Sıçan Karotis Arter Basınç Kontrollü Segmental Balon Yaralanması

Cardiovascular disease remains the leading cause of death and disability worldwide, in part due to atherosclerosis. Atherosclerotic plaque narrows the ...

Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function

Arterial reconstruction, whether angioplasty or bypass surgery, involves iatrogenic trauma causing endothelial disruption and vascular smooth muscle cell (VSMC) proliferation. Common murine models study small vessels such as the carotid and femoral arteries. Herein we describe an in vivo system in which both VSMC proliferation and endothelial barrier function can be simultaneously assessed in a large vessel. We studied the infrarenal aortic response to injury in C57BL/6 mice. The aorta was injured from the left renal vein to the aortic bifurcation by 30 transmural crushes of 5-seconds duration with a cotton-tipped applicator. Morphological changes were assessed with conventional histology. Aorta wall thickness was measured from the luminal surface to the adventitia. EdU integration and counter staining with DAPI and alpha-actin was used to demonstrate VSMC proliferation. Activation of ERK1/2, a known moderator of intimal hyperplasia formation, was determined by Western Blot analysis. The effect of inflammation was determined by immunohistochemistry for B-cells, T-cells, and macrophages. En face sections of endothelium were visualized with scanning electron microscopy (SEM). Endothelial barrier function was determined with Evans Blue staining. Transmural injury resulted in aortic wall thickening. This injury induced VSMC proliferation, most prominently at 3 days after injury, and early activation of ERK1/2 and decreased p27kip1 expression. Injury did not result in increased B-cells, T-cells, or macrophages infiltration in the vessel wall. Injury caused partial endothelial cell denudation and loss of cell-cell contact. Injury resulted in a significant loss of endothelial barrier function, which returned to baseline after seven days. The murine transmural blunt aortic injury model provides an efficient system to simultaneously study both VSMC proliferation and endothelial barrier function in a large vessel.

Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function

Restenosis following cardiovascular procedures (bypass surgery, angioplasty, or stenting) is a significant problem reducing the durability of these procedures. An ideal therapy would inhibit smooth muscle cell (VSMC) proliferation while promoting regeneration of the endothelium. We describe a model for simultaneous assessment of VSMC proliferation and endothelial function in vivo.

Murin Aort Kırma Yaralanması: Verimli<emIn vivo</em&gt; Düz Kas Hücresi çoğalması ve Endotel Fonksiyon Modeli

Arterial reconstruction, whether angioplasty or bypass surgery, involves iatrogenic trauma causing endothelial disruption and vascular smooth muscle cell ...