Yazarlar Boston, MA ilk taslağını düzeltiyorum için redaksiyon ve el yazması düzenleme ve Paskus Yeremya, Boston Çocuk Hastanesi, için, Laurie von Melchner, Bern Üniversitesi Hastanesi, Nöroşirürji Bölümü, Bern, İsviçre teşekkür ederim. Biz Daniel Mettler, DVM, Max Müller, DVM, Daniel Zalokar ve Olgica Beslac, Deneysel Cerrahi Enstitüsü, Klinik Araştırmalar Bölümü, Bern Üniversitesi, Bern, İsviçre hayvan bakımı, anestezi ve ameliyat yardımı usta yönetimini takdir. Biz fizyolojik parametrelerin gerçek zamanlı veri izleme ve post-processing için, Michael Lensch, Baş Araştırma Hemşire, Yoğun Bakım Tıp Anabilim Dalı, Bern Üniversitesi Hastanesi ve Bern Üniversitesi, Bern, İsviçre teşekkür ederim. Biz onların mükemmel laboratuvar teknik ve operatif yardım için, Edin Nevzati Carl Muroi ve Salome Erhardt teşekkür ederiz. Bu çalışma Yoğun Bölümü tarafından desteklenene Care Medicine, Bern Üniversitesi Hastanesi ve Bern, Bern, İsviçre, Klinik Araştırma Bölümü, Bern, Bern, İsviçre Üniversitesi Üniversitesi ve Kantonsspital Aarau, Aarau, İsviçre Araştırma Fonu. Biz Şekil 1 ve 2 için basım izni için, Elsevier teşekkür ederim.

2.5 ağırlığındaki üç aylık dişi Yeni Zelanda tavşanları - 3.5 kg Bu prosedür kullanılmıştır. Çalışma deney hayvanlarının bakımı ve kullanımı için sağlık kuralları National Institutes uygun ve Bern, İsviçre (onay # 105/13) Kantonu Hayvan Bakım Komitesi onayı ile yapıldı. Tüm cerrahi işlemler Bern, İsviçre Bern Üniversitesi Hastanesi&#39;nde Klinik Araştırma Bölümü Deneysel Cerrahi Enstitüsü steril koşullar altında gerçekleştirilmiştir. Bir veteriner cerrahi esnasında anestezi ve geri boyunca hayvanları izlendi. 1. Hayvan Hazırlama, Konumlandırma ve Köprücük Arter Kanülasyon <ol><li> Kas içine ketamin enjeksiyonu ile tavşanda genel anestezi neden (30 mg / kg Ketalar, 50 mg / ml) ve ksilazin (Kg 6 mg / gün; Xylapan 20 mg / ml) zararlı için tavşan tepkisini kontrol ederek ve anestezi kontrol derinliği stimulatiyon (örneğin, ayak tutam). Pozitif karşılık durumunda 1.7 &#39;ye bakınız. </li><li> Her iki gözün alt kapaklarını aşağı çekin ve kuruluk ve tahrişi daha da önlemek için göz kapaklarının için merhem küçük bir miktar uygulanır. </li><li> , 20 Gbutterfly Venflon (20G damar kateteri) ile yanal kulak damar kateterize yapışkan bant ile yapışması ve% 0.9 sodyum klorür ihtiva eden bir ağırlık torbasına (500 ml / 24 saat) ve ketamin bağlantı (40 mg / kg / saat) sürekli damar içine (iv) anesteziye / ksilazin (4 mg / kg / saat). Ek analjezikler her 15 dk iv (Fentanil, 1 mcg / kg) yönetmek. Not: CPP azalma ile ilişkili uçucu gaz anestezikler, CBF artan ve oksijen için serebral metabolik hızı azalan kaçının 11 İntravenöz anestezikler serebral okuyan zaman en üst önem taşımaktadır CBF ve serebral vazokonstriksiyon, 12 koruyarak neuroanesthesia için daha ideal özellikleri sağlamak. vazospazm. Buna ek olarak, her ne kadar ölüm SPONT&#39;da artarerişmesi hayvanlar nefes, daha iyi akut SAK insani durumu taklit edebilir. </li><li> End-tidal karbon dioksit sağlayan bir solunum maskesi ile - (2 L / dk 1) (EtCO 2) izleme oksijen sağlayın. </li><li> Tavşan ventral tarafta bir üçgen düzende 3 kanal elektrokardiyografi (EKG) .Sıra üç cilt altı elektrotlar yükleyin; Özellikle, hem bacaklarda üzerinden dağıtılan alt karın ve iki elektrot (subklavyen arter kanülasyon için steril traş alanına mesafe ile) sağ midthoracic bölge üzerinde bir elektrot yerleştirin. </li><li> Solunum hızı, EKG sinyalinden izlenen kalp hızı (HR) ve zararlı uyarıma reaksiyonu takiben anestezi derinliği ameliyat sırasında her 15 dakikada izleyin. </li><li> Zararlı uyarılmanın (ayak tutam) olumlu yanıt durumunda, ketamin bolus (6 mg / kg) iv ve ksilazin bolus (0.05 mg / kg) iv ve / veya Fentanilin ile ek analjezi bolus (1 mc ile anestezi derinliği uyumg / kg), iv </li><li> Aşağı başını 20 ° eğilebilen ve subklavyen arter maruz kalacağı hangi tarafa hafifçe kontralateral çevirerek, bir vücut ısınma plaka üzerinde yatar pozisyonda tavşan Fix. </li><li> Merhem uygulamak ve klavikula orta üçte sağ göğüs kasının üzerinde saç tıraş tarafından ameliyata alanı hazırlamak ve, verir ön parietal- ve oksipital kafatası, boyun ve sağ femoral arter üzerinde. </li><li> Antiseptik geniş bir spektrumda, örneğin., Povidon-iyot ile 3 dakika boyunca cildi dezenfekte edin. </li><li> Steril levhalar ile tavşan örtün. Damar manipülasyon ve yerel enfeksiyonlar arteriyel vazospazm engellemek üzere topik olarak, steril koşullar altında tüm diğer prosedürleri gerçekleştirmek sık HCI ve antibiyotik solüsyon (neomisin sülfat, 5 mg / ml),% 4, papaverin uygulanır. </li><li> Lokal anestezik (lidokain% 1 maksimum 6 mg / kg) ile pektoral kas sızmak. Bir Parasternal cilt kesi yapmak ve hazırlamakpektoral kas. Mikroskop kullanılarak, subklavian arter incelemek ve maruz sonuna etrafında bir yakın ve uzak dikilen (4-0 polyfilament dikişlerle) ile sabitleyin. Kateter güvenli ve distalde damar Arter yerinde proksimal kontrol yakın bir ligatürün tutun. </li><li> Bir kavisli microscissor ile arter kesisi ile subklavyen arter duvarında bir arteriyotomi gerçekleştirin ve küçük damariçi 3-yollu ile retrograd subklavian arter cannulate. Arteriyel bükülmesini ya arterin proksimali bükme önlemek ve kayma veya masif kanama önlemek için uzak dikilen doğru çift düğüm dikilen tarafından kateter sabitleyin. </li></ol> 2. Tansiyon ve Arter Kan Gazı İzleme <ol><li> I 3-yollu vanasını), damar arteriyel kan gazı için kanül (ABG) analizleri, pH, PaCO2, PaO2, bikarbonat, baz fazlalığı ve SO 2 bağlayın, ii) invaziv arteriyel kanBasınç ölçüm cihazı ve iii) şant cihazı. </li><li> ABG durumu için kan örnekleri (PaCO2, PaO2) toplayın ve sürekli bir Analog- standart kardiyovasküler ve solunum parametreleri (kan basıncı, kalp hızı, EKG, solunum hızı ve tidal sonu CO 2) analog çıkış arayüzü üzerinden veri transfer ve monitör dijital dönüştürücü / veri kaydedici ve mağaza. NOT: basınçları önce ve her seanstan sonra kalp seviyelerde zeroed olacak ve serisi başlamadan önce, analog / dijital dönüştürücü ve veri giriş sistemine basınç kalibrasyonu kez yapılacaktır. </li></ol> 3. Temel Dijital Substraksiyon Anjiyografi <ol><li> Anjiyogramla kalibre için her iki mandibul açıları üzerinde harici bir boyutlandırma cihazı (küçük küre) yerleştirin. NOT: Bu başlangıca post hoc ölçümlerinin kesin karşılaştırılmasına olanak sağlar ve damar çapını izleyin. </li><li> Retrograd içi a göre sayısal çıkarım anjiyografisi (DSA) gerçekleştiriniyonik olmayan iopamidol arasında rterial bolus enjeksiyonu arter yoluyla kanül (0.6 ml / kg, 2 saniye süre ile 5 ml / sn) ve ikinci tıkanmasını önlemek için tuz ile bolus enjeksiyondan hemen sonra kanülün fışkırması. </li><li> 5 ° sol ön oblik pozisyonda hızlı sıralı anjiyografi kayıt kullanılarak Vertebrobaziler sistemin görüntüleri (14 sn 7 görüntüler) edinin. </li><li> Lokal anestetik (% 1 lidokain, maksimum 6 mg / kg) ile sağ femoral arter çevresine enjekte. Küçük bir inguinal cilt kesi olun. Görselleştirme için mikroskop kullanılarak, femoral arter incelemek ve maruz sonuna etrafında bir yakın ve uzak dikilen (4-0 polyfilament dikişlerle) ile sabitleyin. </li><li> Arteriyotomi sonra, 5-F kılıfla femoral artere kanül. Tuzlu su ile kılıfın yan bağlantı noktası yıkayın. </li><li> Floroskopi altında kılıf içinden brakiyosefalik artere 5 F kateter ilerlemek. Bir yol haritası oluşturma, daha sonra th bir kılavuz tel ilerlemeke vertebrobaziler sistem. Adım 3.2 &#39;de tarif edildiği gibi DSA için (0.6 ml / kg, 2 saniyede 5 ml / sn) iyonik olmayan iopamidol bir bolus enjekte edilir. </li></ol> Yüzüstü Pozisyon 4. Rotasyon <ol><li> Bazal DSA ardından, sırtüstü yüzüstü pozisyona tavşan yeniden konumlandırmak. Manipüle veya intra-arteriyel kateter pozisyonunu taşınmaya dikkatli olun. </li><li> Baş aşağı odaklı, 30 ° açıyla bir kafa-tutucu kafa yerleştirin. </li></ol> 5. Cisterna Magna Delinme <ol><li> 1 dakika her biri için Povidon-iyot ile 3 kez baş ve boyun cildi dezenfekte ve steril levhalar ile cerrahi alanı kapsayacak. </li><li> Önceden cilt kesisi veya kas deplasman olmadan transkutanoz sisterna magna içine 22 G x 40 mm pediatrik spinal erişim iğne takın. </li><li> Hayvan tamamıyla kemik dış oksipital çıkıntı boyunca yukarı iğne kaydırarak önce ayak parmağı sıkıştırma tepkisinin olmaması sağlanarak anestezi olduğundan emin olunbir boşluk tespit edilinceye kadar; başka iğne itmeyin. </li><li> Bir kaç dakika boyunca 20 ° açıyla aşağı eğik tavşan kafası ile beyin omurilik sıvısının spontan damlayan gözlemleyerek iğnenin doğru konumlandırılmasını onaylayın. </li></ol> İntrakraniyal Basınç ve Serebral Kan Akışı İzleme 6. Kurulum <ol><li> Orta hat cilt ve galea kesi sonra, küçük bir cerrahi ekartörünü yerleştirin. </li><li> Bir nörolojik görüntüleme, aygıtın yerleştirilmesi için koku ampul ve ikili frontal üzerinde üç tur osteotomiler (2 mm çaplı), dış kafatası noktalarına göre kafatasının ön kısmında yüksek hızlı mikrotur ile (Şekil 1) 9, yani yap Gerekli. Aşağıdaki gibi çapak delik yerleştirme için koordinatlarını belirlemek için bir milimetre çaplı cetvel kullanın: midpupillary hattında Kafa içi basınç (ICP) izleme, midsagittal çizgisinden iki mm bir; intraparenkimal lazer Doppler sondaları4-5 mm ön ve bregmaya yanal (Şekil 1). </li><li> Dura görselleştirmek ve titiz hemostaz gerçekleştirin: kendi tamponad eylem nedeniyle kemik hemostaz için kemik mumu kullanmak ve dura bipolar pıhtılaşmasını kullanarak yerel hemostaz gerçekleştirin. </li><li> 2 mm derinliğe kadar doğru koku ampul içine intraparenkimal intrakranial basınç (ICP) monitör ucu yerleştirin ve sonra kalibre. </li><li> Harici bir kelepçe sistemi kullanarak iki lazer Doppler flowmetre ince iğne probları yerleştirin ve sağ ve sol frontal hemisfer hem de beyin omurilik sıvısı karışmalarını önlemek için orta hatta, ventriküler sistemde, yani lateral olarak gelen çapak deliklerin içine yerleştirin. 2.5 mm derinliğe kadar iğne probları yerleştirin. </li><li> Nörolojik görüntüleme sondaları yerleştirilmesinden sonra kafatası sıvı geçirmez tutmak için kemik mumu kalın bir fiş Tüm Burr deliği mühür. </li><li> Ortalama arteriyel kan basıncı bazal parametreleri ölçmek (MAP), ICP ve mültiparametreli monitör ve dört kanallı lazer Doppler doku kan perfüzyon monitör kullanarak serebral kan akımı (CBF). </li></ol> 7. Şant İndüksiyon <ol><li> Kan dolu basıncı izleme tüp aracılığıyla önceden Kateterize subklavyan arter sisterna magna spinal erişim iğne bağlayın. Kan basıncı ölçümü ve kan örnekleme noktası olarak 3 yollu valf kullanır. Not: SAK şiddeti kan miktarına bağlıdır ve yaklaşık 5,11 beyin hasat zamanında subaraknoid pıhtılarının yaygınlığı ile tahmin edilebilir. </li><li> Sürekli SAK sonrası en az 20 dakika kadar önce 6 dakika 1 Hz örnekleme hızında MAP, HR, EKG, solunum hızı ve sonunu-gelgit CO 2 monitör. </li><li> Hayvan tam subklavyan arter ve sisterna magna basınç Gradie tarafından SAK ikna etmek arasındaki şant bağlantıyı açmadan önce ayak tutam yanıt eksikliği sağlayarak anestezi doğrulayınnt. Not: (örn., ICP arzu edilen bir düzeyde) bir kontrol SAK herhangi bir zaman noktasında şant kapatma ile elde edilebilmektedir. </li><li> Yaklaşık 15 dakikalık bir süre içinde kararlı durum değerlerini kaydedin. </li><li> ICP zirveye ulaşır sonra ICP başlangıç ​​değerlerine yakın bir kararlı duruma dönene kadar, yerinde spinal erişim iğne tutmak. ICP plato fazla 10 sn boyunca muhafaza veya ICP kendiliğinden azalırsa, şant kapatmak durumunda. </li><li> (Ardışık kanama ile kateter manipülasyonu, yüksek morbidite ve mortalite ile ilişkili, ve enfeksiyon oranını artırır çünkü, subklavian kateter dahil) tüm sonda, kemik balmumu ile Burr deliği fiş, CBF ince iğne probları ve ICP prob kaldır titiz yara sulama yapmak neomisin sülfat ve cilt sütür. </li></ol> 8. Ameliyat sonrası Yönetimi <ol><li> İşlem yaklaşık 2 saat sürer. Nedeniyle ketamin ve ksilizin, Anima iyileşme süresi yarı-ömürlerineYaklaşık 1 saat - l oldukça kısadır. Hayvanlar kurtarma sırasında bir ısıtma lambası altında tutulur. Ek sıvılar verilmemektedir. Bu ilk ameliyat sonrası iyileşme aşamasında, buprenorfin, 0.02 mg / kg sc, 24 saat boyunca her 8 saat uygulanır. </li><li> Bir sonraki 72 saat içinde etkin analjezi için, hayvanların boyun bölgesinde traş 12.5 ug / saat serbest transdermal fentanil matris yamaları uygulayın. </li><li> O sternum yatma korumak için yeterli bilince kavuşana kadar gözetimsiz bir hayvan bırakmayın. </li><li> Tamamen iyileşene kadar diğer hayvanların şirket ameliyatı geçirmiş bir hayvan iade etmeyin. </li></ol> 3. Günde DCVS değerlendirin Dijital Çıkartma Anjiyografi takip 9. <ol><li> Yukarıda açıklandığı gibi 3,6 Adımları 1.1 gerçekleştirin. </li><li> Sodyum tiopental intraarteryel bolus enjeksiyonu (40 mg / kg) ile hayvanlar öldürülür (pentotal, Ospedalia AG Hünenberg, İsviçre). Durumlarda histoloji ve immunohist içindeochemistry gereken, 100 cm H2O bir perfüzyon basıncı altında oda sıcaklığında bir kalp içi perfüzyonla fiksasyonu gerçekleştirmek </li></ol>

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J., Jakubowski, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Sheffield+model+of+subarachnoid+hemorrhage+in+rats.">The Sheffield model of subarachnoid hemorrhage in rats.</a> Stroke; a journal of cerebral circulation. 26, 1279-1283 (1995).</li><li>Zakhartchenko, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cell-mediated+transgenesis+in+rabbits:+chimeric+and+nuclear+transfer+animals.">Cell-mediated transgenesis in rabbits: chimeric and nuclear transfer animals.</a> Biology of reproduction. 84, 229-237 (2011).</li><li>Capecchi, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gene+targeting+in+mice:+functional+analysis+of+the+mammalian+genome+for+the+twenty-first+century.">Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century.</a> Nature reviews. Genetics. 6, 507-512 (2005).</li><li>Flisikowska, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficient+immunoglobulin+gene+disruption+and+targeted+replacement+in+rabbit+using+zinc+finger+nucleases.">Efficient immunoglobulin gene disruption and targeted replacement in rabbit using zinc finger nucleases.</a> PloS one. 6, e21045 (2011).</li><li>Nakajima, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+aging+on+cerebral+vasospasm+after+subarachnoid+hemorrhage+in+rabbits.">Effects of aging on cerebral vasospasm after subarachnoid hemorrhage in rabbits.</a> Stroke. 32, 620-628 (2001).</li></ol>

None. The authors have no financial or commercial interest in any of the drugs, materials, or equipment used. No specific funding was received for this work. The authors are solely responsible for the design and conduct of the presented study and report no conflict of interest concerning the materials and methods used in this study or the findings specified in the paper. They confirm the adherence of ethical standards. The study was performed in accordance with the National Institutes of Health guidelines for the care and use of experimental animals and with the approval of the Animal Care Committee of the Canton of Bern, Switzerland (approval #109/07 and #107/09).

Şant modeli akut SAK 3,8,10 sonra insanlarda gözlenene benzer bir patoloji üretir. Bu EBI arttıran korumak ve hatta DCVS 12 tetikleyebilir ve bunlar da bu model, SAH takip EBI ve DCVS etkileşimler de dahil olmak üzere, erken ve geç DCVS fazlar, iki araştırılması için yardımcı olabilir olabileceğini öne sürülmüştür. Özellikle, tekrarlanabilir in vivo DCVS DSA 13 olmak üzere izleme teknikleri, 15 daha readibly küçük laboratuvar hayvanlarında d...

Anevrizmal subaraknoid kanama (SAK) sık sık kalıcı nörolojik hasar veya ölüm 1 yol açan, nöropatolojik tehdit eden koşulların en hayat biridir. Geçmişte araştırma SAK 2 ile ilişkili nörolojik hasarların başlıca etkeni olarak gecikmiş serebral vazospazm (DCVS) odaklanmıştır. Ancak, vazospazm tedavisi sonrası SAK mustarip hastaların genellikle zayıf klinik sonuçları SAK 3 sonrası erken beyin hasarı (EBI) etkilerini içerecek şekilde araştırma odak genişlemesine yol açmıştır. SAK sonrası kötü klinik sonuçlara katkıda EBI ve DCVS hem öneminin daha iyi anlaşılması daha etkin tedavi stratejilerinin geliştirilmesi için esastır. Şimdiye kadar, cisterna magna içine tek ve çift otolog kan enjeksiyonu DCVS 2-6 çalışma için SAK indüksiyonu için standart yöntem olmuştur. Daha önceki çalışmalarda yaygın olarak kullanılan rağmen,Bu model, büyük olasılıkla SAK ile ilişkili nöropatolojık önemli değişiklikleri yeniden değil EBI&#39;ya 7 kaynaklı. Bunun aksine, endovasküler perforasyon kısmen EBI 7 semptomlarını şiddetli akut patofizyolojik değişiklikler üretilmesi bilinmektedir. Bu rapor SAK yeni bir tavşan modeli tarif tekniği ile, standart sisterna magna modeli arter sistemi bağlayarak uyarlanmıştır. Böylece ŞAH-kaynaklı patoloji 8-10 daha doğru karakterizasyonu izin EBI ve DCVS hem soruşturma sağlamak için tasarlanmıştır açıklanır dışı bir köprü aracılığıyla subklavyan arter ve sisterna magna. Kan akışı artar ve tavşan fizyolojisi ile bağlantılıdır ve arteryel kan ve kafatası içi basıncı arasındaki basınç gradyanı ile tahrik edilir. Intraserebral basıncı (ICP) diastolik kan basıncı eşittir ve şant sisteminde kan pıhtılaşır zaman kanama durur. Ana &amp; # kullanılması8217; fizyoloji güvenilir EBI ve DCVS fenotipleri 3,8-10 iki üreten SAK daha tutarlı bir modelini oluşturmak üzere, araştırmacı bağımlı SAK indüksiyon azaltır.

<table border="0" cellpadding="0" cellspacing="0" width="905">
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			<td height="34" style="height:35px;width:279px;">Name</td>
			<td style="width:236px;">Company</td>
			<td style="width:223px;">Catalog Number</td>
			<td style="width:167px;">Comments/Description</td>
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			<td style="width:223px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:279px;">operation microscope</td>
			<td style="width:236px;">Zeiss, Jena, Germany</td>
			<td colspan="2">Zeiss, OPMI-MD surgical microscope</td>
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		<tr height="40">
			<td height="40" style="height:40px;width:279px;">surgical equipment</td>
			<td style="width:236px;">B. Braun, Germany</td>
			<td style="width:223px;">forceps medical n&#176;5, vessel sciccors 8cm, microclip 4mm</td>
			<td></td>
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			<td height="20" style="height:20px;">respirator</td>
			<td style="width:236px;">Hugo Sachs</td>
			<td style="width:223px;"></td>
			<td></td>
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		<tr height="20">
			<td height="20" style="height:20px;">hair clipper</td>
			<td style="width:236px;">3M Surgical Clipper&#160;</td>
			<td style="width:223px;">&#160;Starter Kit 9667A</td>
			<td></td>
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		<tr height="20">
			<td height="20" style="height:20px;">body warm plate</td>
			<td style="width:236px;">FHC</td>
			<td style="width:223px;"></td>
			<td></td>
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		<tr height="40">
			<td height="40" style="height:40px;width:279px;">blood gas analyzer</td>
			<td style="width:236px;">Radiometer, Copenhagen, Denmark</td>
			<td style="width:223px;">ABL 725</td>
			<td></td>
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		<tr height="60">
			<td height="60" style="height:60px;width:279px;">cardiac monitoring</td>
			<td style="width:236px;">Camino Multi-Parameter Monitor, Integra, Plainsboro, NJ, US</td>
			<td style="width:223px;">AP-05</td>
			<td></td>
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		<tr height="60">
			<td height="60" style="height:60px;">software analysis</td>
			<td style="width:236px;">BIOPAC Systems, Inc., Goleta, CA, USA</td>
			<td style="width:223px;">Biopac MP100 and acqKnowledge software,version 3.8.1</td>
			<td></td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;">software analysis</td>
			<td style="width:236px;">ImagePro Discovery, MediaCybernetics, Silver Spring, MD, USA</td>
			<td style="width:223px;">image-Pro Plus version&#160;</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">angiography apparatus</td>
			<td style="width:236px;">DFP 2000 A-Toshiba</td>
			<td style="width:223px;">MIIXR0001EAA</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">ICP monitor</td>
			<td style="width:236px;">Camino Laboratories, San Diego, CA, USA</td>
			<td style="width:223px;">ICP monitor, Model 110-4B</td>
			<td></td>
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		<tr height="20">
			<td height="20" style="height:20px;">blood flow monitor</td>
			<td style="width:236px;">Oxford Optronix Ltd., Oxford, UK</td>
			<td style="width:223px;">CAL KIT microsphere solution</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">laser-Doppler flowmetry fine needle probes&#160;</td>
			<td style="width:236px;">Oxford Optronix Ltd., Oxford, UK</td>
			<td style="width:223px;">MNP110XP, 0.48 mm diameter</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">pressure tube</td>
			<td>B. Braun, Germay</td>
			<td style="width:223px;">PE 1.0 mm &#215; 2.0 mm</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:279px;">anesthesia monitor</td>
			<td>GE Medical Systems, Switzerland&#160;</td>
			<td style="width:223px;">Datex S5 Monitor</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:279px;">Material</td>
			<td style="width:236px;"></td>
			<td style="width:223px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">20 G vascular catheter</td>
			<td style="width:236px;">Smiths Medical</td>
			<td style="width:223px;">Jelco i.v. catheter, REF 4057</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">5.5F three-lumen central venous catheter&#160;</td>
			<td style="width:236px;">Connectors, Tagelswangen, Switzerland</td>
			<td>silicone catheter STH-C040</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">22Gx40mm needle&#160;</td>
			<td style="width:236px;">Emergo Group Inc., Netherlands</td>
			<td style="width:223px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">high-speed microdrill</td>
			<td style="width:236px;">Stryker, Solothurn, Switzerland</td>
			<td>5400-15&#160;</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">bone wax</td>
			<td style="width:236px;">Ethicon, Johnson &#38; Johnson,NJ, USA</td>
			<td style="width:223px;">ETHW31G</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:279px;">bipolar forceps</td>
			<td style="width:236px;">Aesculap, Inc., PA, US</td>
			<td>US349SP&#160;</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:279px;">Ketamin</td>
			<td style="width:236px;"></td>
			<td style="width:223px;"></td>
			<td>Any generic product</td>
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			<td height="20" style="height:20px;">Xylazine</td>
			<td style="width:236px;"></td>
			<td style="width:223px;"></td>
			<td>Any generic product</td>
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			<td style="width:236px;"></td>
			<td style="width:223px;"></td>
			<td>Any generic product</td>
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			<td height="20" style="height:20px;">Fentanyl</td>
			<td style="width:236px;"></td>
			<td style="width:223px;"></td>
			<td>Any generic product</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">transdermal fentanyl matrix patches&#160;</td>
			<td style="width:236px;"></td>
			<td style="width:223px;"></td>
			<td>Any generic product</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Lidocaine 1%&#160;</td>
			<td style="width:236px;"></td>
			<td style="width:223px;"></td>
			<td>Any generic product</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">4% papaverin HCl&#160;</td>
			<td style="width:236px;"></td>
			<td style="width:223px;"></td>
			<td>Any generic product</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Neomycin sulfate&#160;</td>
			<td style="width:236px;">Research Organics Inc., OH, USA</td>
			<td style="width:223px;"></td>
			<td>Any generic product</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Povidone-iodine&#160;</td>
			<td style="width:236px;"></td>
			<td style="width:223px;"></td>
			<td>Any generic product</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">0.9% sodium chloride</td>
			<td style="width:236px;"></td>
			<td style="width:223px;"></td>
			<td>Any generic product</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:279px;">Iopamidol&#160;</td>
			<td style="width:236px;">Abott Laboratories, IL, USA</td>
			<td style="width:223px;"></td>
			<td>Any generic product</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:279px;">3-0 resorbable suture</td>
			<td style="width:236px;">Ethicon Inc., USA</td>
			<td>VCP824G</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:279px;">5-0 non absorbable suture</td>
			<td style="width:236px;">Ethicon Inc., USA</td>
			<td>8618G</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:279px;">4-0 polyfilament sutures</td>
			<td style="width:236px;">Ethicon Inc., USA</td>
			<td style="width:223px;">VCP284G</td>
			<td></td>
		</tr>
	</tbody>
</table>

the rabbit blood-shunt model for the study of acute and late sequelae of subarachnoid hemorrhage: technical aspects

Erken beyin hasarı ve gecikmiş serebral vazospazm hem subaraknoid kanama (SAK) sonrası istenmeyen sonuçlara katkıda bulunur. Her iki koşullarını simüle tekrarlanabilir ve kontrol hayvan modelleri halen nadirdir. Bu nedenle, yeni model SAH&#39;dan Oluşan insan patofizyolojik koşullarda bunların taklit edilmesi için ihtiyaç vardır. Bu rapor, intraserebral basıncın (ICP) kontrol edilmesini sağlayan bir tavşan kanlı-SAK şant modeli teknik nüansları açıklar. Bir ekstrakorporeal şant arteriyel sistemi ve kapalı kafa içinde sınav bağımsız SAK sağlayan subaraknoid, arasına yerleştirilir. Adım adım prosedürel talimatlar ve gerekli ekipman açıklanan, yanı sıra teknik değerlendirmeler minimal mortalite ve morbidite ile model üretmek için. Bu, sağlam, basit ve tutarlı ICP-kontrollü SAK tavşan modelinin başarılı cerrahi yaratılması için gerekli Önemli detaylar açıklanmıştır.

<html> SAK tavşan kanı şant modeli Bu raporda açıklanan, bazal korteks (Şekil 2A, B), ve serebral damar (Şekil 2C) gibi erken 24 olarak saat yaralanma sonrası (B Şekil 2A) hipokampus EBI&#39;ya üreten ve karakteristik gösterir kan dağılımı (Şekil 2B) 8. Buna ek olarak, model SAK uyandırmasıyla (Şekil 3) 10 gün sonra, üç ile DCVS şiddetli derecede orta tetikler. Akut SAK sırasında solunum dur...

Watch this Scientific Journal Video about The Rabbit Blood-shunt Model for the Study of Acute and Late Sequelae of Subarachnoid Hemorrhage: Technical Aspects at JoVE.com

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

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.

Subaraknoid Kanama Akut ve Geç sekeli Çalışmaları Tavşan Kan şant Modeli: Teknik Yönleri

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

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13.5K Görüntüleme.  University and Bern University Hospital (Inselspital). The experimental intracranial pressure-controlled blood shunt subarachnoid hemorrhage (SAH) model in the rabbit combines the standard procedures — 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.

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

Microsurgical Venous Pouch Arterial-Bifurcation Aneurysms in the Rabbit Model: Technical Aspects

For ruptured human cerebral aneurysms endovascular embolization has become an equivalent alternative to aneurysm clipping.1 However, large clinical trials have shown disappointing long-term results with unacceptable high rates of aneurysm recanalization and delayed aneurysm rupture.2 To overcome these problems, animal experimental studies are crucial for the development of better endovascular devices.3-5
Several animal models in rats, rabbits, canines and swine are available.6-8 Comparisons of the different animal models showed the superiority of the rabbit model with regard to hemodynamics and comparability of the coagulation system and cost-effectiveness.9-11 
The venous pouch arterial bifurcation model in rabbits is formed by a venous pouch sutured into an artificially created true bifurcation of both common carotid arteries (CCA). The main advantage of this model are true bifurcational hemodynamics.12 The major drawbacks are the sofar high microsurgical technical demands and high morbidity and mortality rates of up to 50%.13 These limitations have resulted in less frequent use of this aneurysm model in the recent years. These shortcomings could be overcome with improved surgical procedures and modified peri- and postoperative analgetic management and anticoagulation.14-16 Our techniques reported in this paper demonstrate this optimized technique for microsurgical creation of arterial bifurcation aneurysms.

An optimized technique for the microsurgical creation of arterial bifurcation aneurysms mimicking bifurcation human cerebral aneurysms is described. A venous pouch is sutured into an artificially created true bifurcation of both common carotid arteries. Facilitated microsurgical techniques and aggressive postoperative anticoagulation and analgesia lead to minimized morbidity rates and high aneurysm patency rates.

Tavşan Modelinde Mikrocerrahi Venöz Kılıfı Arter Bifurkasyon Anevrizmalarının: Teknik Yönleri

For ruptured human cerebral aneurysms endovascular embolization has become an equivalent alternative to aneurysm clipping.1 However, large clinical trials ...

Tıp

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for objective diagnosis but also for the evaluation of therapeutic efficacy and resilience to trauma. Ongoing research is directed at identifying molecular biomarkers for PTSD, including traumatic stress induced proteins, transcriptomes, genomic variances and genetic modulators, using biologic samples from subjects' blood, saliva, urine, and postmortem brain tissues. However, the correlation of these biomarker molecules in peripheral or postmortem samples to altered brain functions associated with psychiatric symptoms in PTSD remains unresolved. Here, we present an animal model of PTSD in which both peripheral blood and central brain biomarkers, as well as behavioral phenotype, can be collected and measured, thus providing the needed correlation of the central biomarkers of PTSD, which are mechanistic and pathognomonic but cannot be collected from people, with the peripheral biomarkers and behavioral phenotypes, which can.
Our animal model of PTSD employs restraint and tail shocks repeated for three continuous days - the inescapable tail-shock model (ITS) in rats. This ITS model mimics the pathophysiology of PTSD 17, 7, 4, 10. We and others have verified that the ITS model induces behavioral and neurobiological alterations similar to those found in PTSD subjects 17, 7, 10, 9. Specifically, these stressed rats exhibit (1) a delayed and exaggerated startle response appearing several days after stressor cessation, which given the compressed time scale of the rat's life compared to a humans, corresponds to the one to three months delay of symptoms in PTSD patients (DSM-IV-TR PTSD Criterian D/E 13), (2) enhanced plasma corticosterone (CORT) for several days, indicating compromise of the hypothalamopituitary axis (HPA), and (3) retarded body weight gain after stressor cessation, indicating dysfunction of metabolic regulation.
The experimental paradigms employed for this model are: (1) a learned helplessness paradigm in the rat assayed by measurement of acoustic startle response (ASR) and a charting of body mass; (2) microdissection of the rat brain into regions and nuclei; (3) enzyme-linked immunosorbent assay (ELISA) for blood levels of CORT; (4) a gene expression microarray plus related bioinformatics tools 18. This microarray, dubbed rMNChip, focuses on mitochondrial and mitochondria-related nuclear genes in the rat so as to specifically address the neuronal bioenergetics hypothesized to be involved in PTSD.

We describe a rat model of post traumatic stress disorder (PTSD) that reveals the persistent alterations in neuroendocrine function and the delayed long-term, exaggerated fear response, characteristic of PTSD patients. The animal model and methods described here are useful for correlating biomarkers in brain nuclei, which are mechanistic but cannot be measured in patients, with biomarkers in peripheral white blood cells, which can.

TSSB, Nöral Hematolojik ve Davranış Bağlantılı Revealing için Hayvan Modelinde Biyobelirteçler

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for ...

NADH Fluorescence Imaging of Isolated Biventricular Working Rabbit Hearts

Since its inception by Langendorff1, the isolated perfused heart remains a prominent tool for studying cardiac physiology2. However, it is not well-suited for studies of cardiac metabolism, which require the heart to perform work within the context of physiologic preload and afterload pressures. Neely introduced modifications to the Langendorff technique to establish appropriate left ventricular (LV) preload and afterload pressures3. The model is known as the isolated LV working heart model and has been used extensively to study LV performance and metabolism4-6. This model, however, does not provide a properly loaded right ventricle (RV). Demmy et al. first reported a biventricular model as a modification of the LV working heart model7, 8. They found that stroke volume, cardiac output, and pressure development improved in hearts converted from working LV mode to biventricular working mode8. A properly loaded RV also diminishes abnormal pressure gradients across the septum to improve septal function. Biventricular working hearts have been shown to maintain aortic output, pulmonary flow, mean aortic pressure, heart rate, and myocardial ATP levels for up to 3 hours8.
When studying the metabolic effects of myocardial injury, such as ischemia, it is often necessary to identify the location of the affected tissue. This can be done by imaging the fluorescence of NADH (the reduced form of nicotinamide adenine dinucleotide)9-11, a coenzyme found in large quantities in the mitochondria. NADH fluorescence (fNADH) displays a near linearly inverse relationship with local oxygen concentration12 and provides a measure of mitochondrial redox state13. fNADH imaging during hypoxic and ischemic conditions has been used as a dye-free method to identify hypoxic regions14, 15 and to monitor the progression of hypoxic conditions over time10.
The objective of the method is to monitor the mitochondrial redox state of biventricular working hearts during protocols that alter the rate of myocyte metabolism or induce hypoxia or create a combination of the two. Hearts from New Zealand white rabbits were connected to a biventricular working heart system (Hugo Sachs Elektronik) and perfused with modified Krebs-Henseleit solution16 at 37 &deg;C. Aortic, LV, pulmonary artery, and left &amp; right atrial pressures were recorded. Electrical activity was measured using a monophasic action potential electrode. To image fNADH, light from a mercury lamp was filtered (350&plusmn;25 nm) and used to illuminate the epicardium. Emitted light was filtered (460&plusmn;20 nm) and imaged using a CCD camera. Changes in the epicardial fNADH of biventricular working hearts during different pacing rates are presented. The combination of the heart model and fNADH imaging provides a new and valuable experimental tool for studying acute cardiac pathologies within the context of realistic physiological conditions.

The objective is to monitor the mitochondrial redox state of isolated hearts within the context of physiologic preload and afterload pressures. A biventricular working rabbit heart model is presented. High spatiotemporal resolution fluorescence imaging of NADH is used to monitor the mitochondrial redox state of epicardial tissue.

İzole Biventriküler ve NADH Floresans Görüntüleme Tavşan Kalpler Çalışma

Since its inception by Langendorff1, the isolated perfused heart remains a prominent tool for studying cardiac physiology2. However, it is not well-suited ...

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.

Deneysel Subaraknoid Kanama Sonrası Gecikmeli Serebral Vazospazm değerlendirin A Düşük Mortalite Rat Modeli

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

Human Neuroendocrine Tumor Cell Lines as a Three-Dimensional Model for the Study of Human Neuroendocrine Tumor Therapy

Neuroendocrine tumors (NETs) are rare tumors, with an incidence of two per 100,&#x200A;000 individuals per year, and they account for 0.5% of all human malignancies.1 Other than surgery for the minority of patients who present with localized disease, there is little or no survival benefit of systemic therapy. Therefore, there is a great need to better understand the biology of NETs, and in particular define new therapeutic targets for patients with nonresectable or metastatic neuroendocrine tumors. 3D cell culture is becoming a popular method for drug screening due to its relevance in modeling the in vivo tumor tissue organization and microenvironment.2,3 The 3D multicellular spheroids could provide valuable information in a more timely and less expensive manner than directly proceeding from 2D cell culture experiments to animal (murine) models.
To facilitate the discovery of new therapeutics for NET patients, we have developed an in vitro 3D multicellular spheroids model using the human NET cell lines. The NET cells are plated in a non-adhesive agarose-coated 24-well plate and incubated under physiological conditions (5% CO2, 37 &deg;C) with a very slow agitation for 16-24 hr after plating. The cells form multicellular spheroids starting on the 3rd or 4th day. The spheroids become more spherical by the 6th day, at which point the drug treatments are initiated. The efficacy of the drug treatments on the NET spheroids is monitored based on the morphology, shape and size of the spheroids with a phase-contrast light microscope. The size of the spheroids is estimated automatically using a custom-developed MATLAB program based on an active contour algorithm. Further, we demonstrate a simple method to process the HistoGel embedding on these 3D spheroids, allowing the use of standard histological and immunohistochemical techniques. 
This is the first report on generating 3D spheroids using NET cell lines to examine the effect of therapeutic drugs. We have also performed histology on these 3D spheroids, and displayed an example of a single drug's effect on growth and proliferation of the NET spheroids. Our results support that the NET spheroids are valuable for further studies of NET biology and drug development.

We present a simple agarose overlay platform to grow 3D multicellular spheroids using neuroendocrine cancer cell lines. This method provides a very convenient way to examine the effect of therapeutic drugs on the neuroendocrine tumor cells. It could also help us establish human neuroendocrine tumor spheroids for cancer therapy.

İnsan Nöroendokrin Tümör Terapi Çalışmaları Üç Boyutlu Model İnsan nöroendokrin tümör hücre hatlarında

Neuroendocrine tumors (NETs) are rare tumors, with an incidence of two per 100,&#x200A;000 individuals per year, and they account for 0.5% of all human ...

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 ...

Technical Aspects of the Mouse Aortocaval Fistula

Technical aspects of creating an arteriovenous fistula in the mouse are discussed. Under general anesthesia, an abdominal incision is made, and the aorta and inferior vena cava (IVC) are exposed. The proximal infrarenal aorta and the distal aorta are dissected for clamp placement and needle puncture, respectively. Special attention is paid to avoid dissection between the aorta and the IVC. After clamping the aorta, a 25 G needle is used to puncture both walls of the aorta into the IVC. The surrounding connective tissue is used for hemostatic compression. Successful creation of the AVF will show pulsatile arterial blood flow in the IVC. Further confirmation of successful AVF can be achieved by post-operative Doppler ultrasound.

The goal is to produce an arteriovenous fistula that is simple and reproducible. This method does not use sutures or glue adhesive. Therefore the samples can be used with the least amount of foreign materials for analysis.

Fare Aortocaval Fistül Teknik Yönleri

Technical aspects of creating an arteriovenous fistula in the mouse are discussed. Under general anesthesia, an abdominal incision is made, and the aorta ...

A Murine Model of Subarachnoid Hemorrhage

In this video publication a standardized mouse model of subarachnoid hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of Willis perforation (CWp) and proven by intracranial pressure (ICP) monitoring. Thereby a homogenous blood distribution in subarachnoid spaces surrounding the arterial circulation and cerebellar fissures is achieved. Animal physiology is maintained by intubation, mechanical ventilation, and continuous on-line monitoring of various physiological and cardiovascular parameters: body temperature, systemic blood pressure, heart rate, and hemoglobin saturation. Thereby the cerebral perfusion pressure can be tightly monitored resulting in a less variable volume of extravasated blood. This allows a better standardization of endovascular filament perforation in mice and makes the whole model highly reproducible. Thus it is readily available for pharmacological and pathophysiological studies in wild type and genetically altered mice.

A standardized mouse model of subarachnoid hemorrhage by intraluminal Circle of Willis perforation is described. Vessel perforation and subarachnoid bleeding are monitored by intracranial pressure monitoring. In addition various vital parameters are recorded and controlled to maintain physiologic conditions.

Subaraknoid Kanama bir fare modeli

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 Arterial Restenosis: Technical Aspects of Femoral Wire Injury

Cardiovascular disease caused by atherosclerosis is the leading cause of death in the developed world. Narrowing of the vessel lumen, due to atherosclerotic plaque development or the rupturing of established plaques, interrupts normal blood flow leading to various morbidities such as myocardial infarction and stroke. In the clinic endovascular procedures such as angioplasty are commonly performed to reopen the lumen. However, these treatments inevitably damage the vessel wall as well as the vascular endothelium, triggering an excessive healing response and the development of a neointimal plaque that extends into the lumen causing vessel restenosis (re-narrowing). Restenosis remains a major cause of failure of endovascular treatments for atherosclerosis. Thus, preclinical animal models of restenosis are vitally important for investigating the pathophysiological mechanisms as well as translational approaches to vascular interventions. Among several murine experimental models, femoral artery wire injury is widely accepted as the most suitable for studies of post-angioplasty restenosis because it closely resembles the angioplasty procedure that injures both endothelium and vessel wall. However, many researchers have difficulty utilizing this model due to its high degree of technical difficulty. This is primarily because a metal wire needs to be inserted into the femoral artery, which is approximately three times thinner than the wire, to generate sufficient injury to induce prominent neointima. Here, we describe the essential surgical details to effectively overcome the major technical difficulties of this model. By following the presented procedures, performing the mouse femoral artery wire injury becomes easier. Once familiarized, the whole procedure can be completed within 20 min.

The mouse femoral artery wire injury model of restenosis is technically challenging. In this protocol we show the key technical details essential for successfully performing wire injury to induce consistent&#160;neointima for studies of restenosis.

Arter Restenozun bir fare modeli: Femur Tel Yaralanma Teknik Yönleri

Cardiovascular disease caused by atherosclerosis is the leading cause of death in the developed world. Narrowing of the vessel lumen, due to ...

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.

İzometrik Contractility ölçüm tel Myography kullanarak fare mezenterik arter

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...