Güncel araştırma Solorz-Zak Araştırma Vakfı tarafından finanse edilmektedir.

Tüm cerrahi işlemler etik incelemeye tabi ve Yukarı Bavyera hükümeti (referans numarası: 55.2-1-54-2532.3-13-13 ve -2532-136-11) tarafından onaylanmıştır. Hayvanlar yaklaşık 25 g bir vücut ağırlığına sahip erkek C57BL / 6 fareleri bulunmaktadır. 1.. Hayvan Preparasyon <ol><li> Bir odacık içine fare koyarak anestezi neden. Hayvan bilincini kaybedene kadar% 5 izofluran ile odasını yıkayın. </li><li> Periton boşluğu içine enjekte edilir, önceden karıştırılmış anestezi: fentanil (0.05 mg / kg), midazolam (5 mg / kg) ve medetomidin (0.5 mg / kg). İşlem sırasında önce ve düzenli olarak refleksleri kontrol edin. Anesteziyi muhafaza etmek üzere saat başı başlangıç ​​miktarının üçte birini yeniden enjekte. </li><li> Bir 20 G venöz kateter 11 yapılmış bir tüp ile orotracheally entübasyon. Entübasyon eğimli bir platform (30 °) üzerinde hayvan düzeltmek için, bükülmüş forseps ile dilini geri operasyon mikroskobu altında ses telleri görselleştirmek ve trakea içine tüp takıninspirasyon sırasında. </li><li> Yüzükoyun pozisyonda fare yerleştirin ve pamuklu bir parça veya bir microcapnograph ile tüpün doğru yerleşimini kontrol edin. </li><li> Respiratöre entübasyon tüpü bağlayın. 180-220 nefes / dak ve 200-250 ul bir vuruş hacmi bir frekans ile% 25 oksijen ile takviye oda havası ile fare havalandırın. </li><li> Microcapnograph için entübasyon tüpü bağlayın. Havalandırma frekansını ayarlayarak 30 mmHg son ekspirasyon pCO 2 koruyun. </li><li> Bir rektal sıcaklık probu yerleştirin ve 37 ° C iç vücut ısısını korumak için de bir ısıtma pedi üzerine hayvan. </li><li> Sağ arka pençe üzerinde halka şeklindeki Pulsoximeter sensörü uygulanır. </li><li> Bir makas ile kafatası üzerinde cildi açın. Kesi yaklaşık 0.5 cm uzunluğunda ve kulak ve gözün arasında olmalıdır. </li><li> Temporal kemik bir neşter ile sol temporal kas teşrih. </li><li> Lazer Doppler debimetre (LDF) prob tutkalsol temporal kemik. Tutkal sertleşir kadar sabit bir pozisyonda probu tutun. </li><li> Sol temporal kemik içine bir diş matkap ile yaklaşık 1.5 mm çapında bir delik delin. Isı hasarı önlemek için tuzlu su ile kemik soğutun. </li><li> Kafatası boşluğunun içine ICP probu yerleştirin. Beyin doku hasarı ve kanama önlemek için dorsal mümkün olduğunca ileri itin. </li><li> Prob doğru pozisyonda ise, düzeltmek, ve çimento ile mühür. 5 dakika için çimento kurumasını bekleyin. </li><li> Sırtüstü pozisyonda dikkatle fareyi çevirin. </li><li> Sürekli kan basıncı izlenmesi için, sol femoral arter kateterize. </li><li> Kan basıncı izleme cihazı için femoral kateter bağlayın. </li></ol> 2. SAK İndüksiyon <ol><li> Çene sternum bir makasla (2 cm) ile deriyi açın. Açık açık bağ dokusunu incelemek ve bir kenara tükürük bezleri itin. </li><li> Sol karotis arter (CCA) ortaya çıkarmak ve harekete geçirmek. KoruCCA gibi aynı bağ dokusu kılıf çalışır vagus siniri,. Kranial Taşı ve aynı tekniği kullanarak ICA ve ECA ortaya çıkarmak ve harekete. </li><li> Kadar cranially mümkün ECA Arter. </li><li> ECA&#39;nın etrafında filament için iki tane daha önceden düzenlemek ligasyonu. </li><li> Microclips ile geçici CCA ve ICA tıkamak. Bir mikroklip aplikatör ile microclips yerleştirin. Klipleri nazikçe geri çekerek doğru uygulanır emin olun. </li><li> Bir gemi makas ile ECA içine filament yerleştirilmesi için bir delik açın. </li><li> ECA içine 12 mm uzunluğa sahip bir Prolene 5-0 filament yerleştirin. </li><li> Bir danışıklı ligasyonu ile ekleme siteyi kapatın. </li><li> CCA ve ICA bir mikroklip aplikatör ile microclips çıkarın. </li><li> ICP yükselir kadar ICA içine bir forseps ile filament ilerlemek. ICP ani yükselişi kanama uyarıldığını gösterir. </li><li> Hemen filamanın çekiniz ve pr hem kapatarak ECA Arterardışık earranged ligasyonu. Bu ekleme sitenin dışında kanama önler. </li><li> Cilt yarayı dikin. </li><li> Başka bir 20 dakika boyunca hayvanın fizyolojik parametreleri izlemek. </li><li> ICP ve LDF probları kaldırmak ve cilt yara sütür. </li></ol> 3. Deney Sonu <ol><li> PBS içinde 20 ml% 4 PFA (4 ° C) ve ardından tuzlu su (oda sıcaklığı) 20 ml transcardially hayvan serpmek. </li><li> Kafatasının dışında beyin teşrih. Orta hatta ve yörünge boşlukların arasındaki kafatası kesti. Daha sonra beyinden gelen kemik soyun. </li><li> Subaraknoid aralığa kan dağılımını değerlendirmek. </li></ol> 4. Survival Cerrahi Durumunda Düşünceler (video gösterilmemiştir) <ol><li> Doğrudan anestezi indüksiyon sonrası postoperatif analjezi için Carprofen (4 mg / kg subkutan) enjekte edilir. Postoperatif gözlem süresi boyunca Carprofen (4 mg / kg deri altından), her 24 saat enjekte edilir. </li&gt; <li> Bunun yerine invaziv kan basıncı ölçümü invaziv olmayan kan basıncı izleme sistemi kullanır. </li><li> Nalokson (1.2 mg / kg), flumazenil (0.5 mg / kg) ve atipamezol (2.5 mg / kg) deri altından maddeler antagonize anestezi enjektö sonlandırılması için. </li><li> Hayvan ekstübe. </li><li> Refleksleri kazanmak sonra önceden ısıtılmış odasına hayvan koymak. 24 saat boyunca, yaklaşık 32 ° C &#39;de hayvan tutun. </li><li> Hayvanlar ameliyattan sonra ilk saatlerde spontan solunum ve genel durum düzenli olarak kontrol edilir. Beyin sapı etkilenen ise hayvanların solunum problemleri ve ötenazi olmalı. </li><li> Hayvanlar genel durumu ve vücut ağırlığı gibi nörolojik ve duyu eksikliklerinin 15 için her gün kontrol edilir. </li></ol>

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Res. 24, 510-516 (2002).</li><li>Broderick, J. P., Brott, T. G., Duldner, J. E., Tomsick, T., Leach, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Initial+and+recurrent+bleeding+are+the+major+causes+of+death+following+subarachnoid+hemorrhage.">Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage.</a> Stroke. 25, 1342-1347 (1994).</li><li>Thal, S. C., Plesnila, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Non-invasive+intraoperative+monitoring+of+blood+pressure+and+arterial+pCO2+during+surgical+anesthesia+in+mice.">Non-invasive intraoperative monitoring of blood pressure and arterial pCO2 during surgical anesthesia in mice.</a> J. Neurosci. Methods. 159, 261-267 (2007).</li><li>Hockel, K., Trabold, R., Scholler, K., Torok, E., Plesnila, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+anesthesia+on+pathophysiology+and+mortality+following+subarachnoid+hemorrhage+in+rats.">Impact of anesthesia on pathophysiology and mortality following subarachnoid hemorrhage in rats.</a> Exp. Transl. Stroke Med. 4, 5 (2012).</li><li>Wang, Z., Schuler, B., Vogel, O., Arras, M., Vogel, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=What+is+the+optimal+anesthetic+protocol+for+measurements+of+cerebral+autoregulation+in+spontaneously+breathing+mice?.">What is the optimal anesthetic protocol for measurements of cerebral autoregulation in spontaneously breathing mice?.</a> Exp. Brain Res. 207, 249-258 (2010).</li><li>Schwartz, A. Y., Masago, A., Sehba, F. A., Bederson, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+models+of+subarachnoid+hemorrhage+in+the+rat:+a+refinement+of+the+endovascular+filament+model.">Experimental models of subarachnoid hemorrhage in the rat: a refinement of the endovascular filament model.</a> J. Neurosci. Methods. 96, 161-167 (2000).</li><li>Feiler, S., Plesnila, N., Thal, S. C., Zausinger, S., Scholler, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contribution+of+matrix+metalloproteinase-9+to+cerebral+edema+and+functional+outcome+following+experimental+subarachnoid+hemorrhage.">Contribution of matrix metalloproteinase-9 to cerebral edema and functional outcome following experimental subarachnoid hemorrhage.</a> Cerebrovasc. Dis. 32, 289-295 (2011).</li></ol>

Yazarlar ifşa hiçbir şey yok.

SAK sonrası tedavi seçenekleri kısıtlı ve çoğunlukla etkisiz vardır. Bu nedenle post-hemorajik beyin hasarının patofizyolojisi daha yeni tedavi hedefleri belirlemek ve yeni tedavi yaklaşımları geliştirmek için anlaşılması gerekir. Standardize ve genetiği değiştirilmiş hayvanlar, yani farelerde, iyi tekrarlanabilir hayvan modelleri gibi soruşturma için çok önemlidir. Yakından insanlarda patofizyolojiye benzer olarak cwp modeli SAK için yaygın olarak kullanılan bir model haline gelmi...

SAK hastalar için en yararlı sonuç ile inme alt tipi olduğu: Hastaların% 40 kanama 1 sonra bir ay içinde ölür ve hayatta kalanlar nadiren klinik olarak olumlu bir sonuç var. Spontan UAHS (% 80) büyük çoğunluğu, çoğunlukla arter, baziler arter ve orta serebral arter (MCA) 2 iletişim anterior ve posterior boyunca yer intrakranial anevrizmaların yırtılması kaynaklanır. Bu anevrizma hayvanlarda Modele zordur ve bu nedenle SAK hayvan modelleri ya da subaraknoid boşluk / beyin veya ventriküllere subaraknoid kabın endovasküler delme ile kan enjeksiyonu ile gerçekleştirilir. Kan hacmi doğrudan 3 kontrol edilebilir gibi cisterna magna içine otolog kan enjeksiyonu yapmak kolay ve tekrarlanabilir. Ne yazık ki SAK fizyopatolojinin bazı yönleri, örneğindamar yaralanması, bu prosedür ile model olamaz. SAK indüksiyonu için başka bir teknik yaklaşım, bir intrasisternal ven 4 açılmasıdır. Ancak, MCA şube intraluminal CWP modelleri insanlarda patofizyolojisi en yakın 5 prosedür olarak görünmektedir. Yöntem, Veelken ve arkadaşları 6,7 ile Bederson ve arkadaşları tarafından ve aynı zamanda geliştirilmiş ve ilk olarak sıçanlarda tarif edilmiştir. Daha sonra intraluminal perforasyon modeli farelere 8,9 uyarlanmıştır. Bir filament dış karotid arter (ECA) içine sokulur ve iç karotid arter (ICA) ile kafa tabanına ilerletilir. MCA dallanma noktasında filaman gemi deler ve kafatası tabanında subaraknoid boşluk içine bir kanama neden olur. Kan daha sonra çatlamalar ve kan damarları boyunca kalan subaraknoid alana dağıtır. Kanama perforasyon yerinde pıhtı oluşumu durdu, ama rebleedings, WH edilirich hastalarda 10, oluşabilir genellikle zararlıdır. Buna göre, endovasküler lif modeli son yıllarda yaygın olarak kullanılan SAK modeli oldu. Filaman perforasyon modelinde en sık bahsedilen dezavantajı kanama hacmi doğrudan kontrol edilemeyen ve bu nedenle de değişken olabilir olmasıdır. Bu değişkenlik anlamlı hayvan fizyolojisi ve post-hemorajik ICP sıkı kontrolü ile azaltılabilir. Fareler, genetik olarak modifiye edilmiş suşların çok sayıda mevcut olan büyük avantaj vardır. Ancak, küçük boyutları için cerrahi işlemler büyük türleri, örneğin, sıçan ya da tavşan daha karmaşık olma eğilimindedir. Bu nedenle farelere sıçanlar için geliştirilen tekniklerin küçültülür genellikle fareler hemoglobin saturasyonu ve kalp hızı izleme için çok sınırlı bir vücut ağırlığı ve kan hacmi noninvaziv kan basıncı ve kan gazı analizi için teknikleri yanı sıra gibi örneğin istenen sonuçlara yol açmazmümkün uygulanmalıdır. Buna uygun olarak, mevcut yayının amacı farelerde SAK için filaman delme modeli tanımlamak için ve bu model bir standart ve yüksek ölçüde tekrarlanabilir biçimde yapılabilir ne kadar göstermektir.

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

a murine model of subarachnoid hemorrhage

Bu Video yayında subaraknoid kanama (SAK), standart bir fare modeli sunulmuştur. Kanama Willis perforasyon (KİP) endovasküler Çemberi tarafından uyarılan ve intrakranial basınç (ICP) izleme ile kanıtlanmıştır. Böylece arteriyel dolaşımı çevreleyen subaraknoid boşluk ve serebellar çatlaklar homojen bir kan dağılımı elde edilir. Vücut ısısı, sistemik kan basıncı, kalp hızı ve hemoglobin doygunluk: Hayvan Fizyolojisi, entübasyon, mekanik ventilasyon, ve çeşitli fizyolojik ve kardiyovasküler parametreler sürekli on-line izleme tarafından yapılmaktadır. Bu şekilde serebral perfüzyon basıncı sıkı bir şekilde ekstravaze kan daha az değişken bir hacim içinde elde izlenebilir. Bu farelerde endovasküler filament perforasyon daha iyi standardizasyonu sağlar ve tüm model yüksek tekrarlanabilir yapar. Bu nedenle, vahşi tip ve genetik ve farmakolojik çalışmaları için patofizyolojik hazırly değişmiş fareler.

Ölüm oranı Cerrahi teknik hakim sonra prosedür ameliyat sırasında hiçbir ölüm temin etmez. Aynı zamanda kanama hemen hemen bütün hayvanlarda elde edilebilir. Postoperatif mortalite hayvanların çoğu ameliyattan sonra (Şekil 5) 1. gün ölüyor ile% 30-40 olduğunu. ICP SAK sonrası değerleri Kanama önce ICP yaklaşık 4 mmHg. 120 mmHg ICP keskin bir artış sonuçlar kanama. ICP değerler daha sonra, 5 daki...

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

A Murine Model of Subarachnoid Hemorrhage

Willis perforasyon intralüminal Circle subaraknoid kanama standartlaştırılmış bir fare modeli tarif edilmektedir. Gemi perforasyon ve subaraknoid kanama intrakranial basınç izleme tarafından izlenir. Buna ek olarak, çeşitli çok önemli parametreler kaydedilir ve fizyolojik koşulları sağlamak için kontrol edilir.

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 ...

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JoVE Journal

Medicine

19.5K Görüntüleme.  University of Munich Medical Center.  Willis perforasyon intralüminal Circle subaraknoid kanama standartlaştırılmış bir fare modeli tarif edilmektedir. Gemi perforasyon ve subaraknoid kanama intrakranial basınç izleme tarafından izlenir. Buna ek olarak, çeşitli çok önemli parametreler kaydedilir ve fizyolojik koşulları sağlamak için kontrol edilir. 

Video: A Murine Model of Subarachnoid Hemorrhage

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

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

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

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) ...

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Murine Model of Wound Healing

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

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

Yara Şifa murin Modeli

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

A New Murine Model of Endovascular Aortic Aneurysm Repair

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

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

Endovasküler Aort Anevrizma Onarımı Yeni Bir murin Modeli

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

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

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

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

İntraserebral Kanama Fare Modellerinden olarak Otolog Blood veya Klostridyal Kollajenazının intrastriatal Enjeksiyon

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

A Preclinical Murine Model of Hepatic Metastases

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

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

Karaciğer metastazları Klinik öncesi fare modeli

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

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

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

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

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 ...

A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction

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

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

Geri dönüşümsüz ve Tersinir Tek taraflı Üreterik Obstrüksiyon bir fare modeli

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

Pre-clinical Orthotopic Murine Model of Human Prostate Cancer

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

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

İnsan Prostat Kanseri klinik öncesi Ortotopik murin modeli

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

Integrated Compensatory Responses in a Human Model of Hemorrhage

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

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

Kanama İnsan Modeli Entegre Telafi Cevapları

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

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

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 ...