The authors are solely responsible for the design and conduct of the presented study. Dr. Marbacher was supported by a grant from the Swiss National Science Foundation (PBSKP3-123454). The authors declare no conflict of interests. 
Author contributions to the study and manuscript preparation include the following. Conception and design: SM, JM, JF. Acquisition of data: SM, EA, JF. Analysis and interpretation of data: SM, JF, JM. Drafting the article: SM, JF, JM. Critically revising the article: JH, MN. Statistical analysis: SM, JF. Study supervision: JF, JH, MN.

<ol>
	<li>Bouzeghrane, F., 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=In+vivo+experimental+intracranial+aneurysm+models:+a+systematic+review.">In vivo experimental intracranial aneurysm models: a systematic review.</a> AJNR Am J Neuroradiol. 31, 418-423 (2010).</li><li>Marbacher, S., 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=Complex+bilobular,+bisaccular,+and+broad-neck+microsurgical+aneurysm+formation+in+the+rabbit+bifurcation+model+for+the+study+of+upcoming+endovascular+techniques.+AJNR.">Complex bilobular, bisaccular, and broad-neck microsurgical aneurysm formation in the rabbit bifurcation model for the study of upcoming endovascular techniques. AJNR.</a> American journal of neuroradiology. 32, 772-777 (2011).</li><li>Frosen, J., 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=Contribution+of+mural+and+bone+marrow-derived+neointimal+cells+to+thrombus+organization+and+wall+remodeling+in+a+microsurgical+murine+saccular+aneurysm+model.">Contribution of mural and bone marrow-derived neointimal cells to thrombus organization and wall remodeling in a microsurgical murine saccular aneurysm model.</a> Neurosurgery. 58, 936-944 (2006).</li><li>Marjamaa, J., 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=Mice+with+a+deletion+in+the+first+intron+of+the+Col1a1+gene+develop+dissection+and+rupture+of+aorta+in+the+absence+of+aneurysms:+high-resolution+magnetic+resonance+imaging.">Mice with a deletion in the first intron of the Col1a1 gene develop dissection and rupture of aorta in the absence of aneurysms: high-resolution magnetic resonance imaging.</a> at 4.7 T, of the aorta and cerebral arteries. Magn Reson Med. 55, 592-597 (2006).</li><li>Oyamada, S., 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=Trans-iliac+rat+aorta+stenting:+a+novel+high+throughput+preclinical+stent+model+for+restenosis+and+thrombosis.">Trans-iliac rat aorta stenting: a novel high throughput preclinical stent model for restenosis and thrombosis.</a> The Journal of surgical research. , 166-191 (2011).</li><li>Lowe, H. C., James, B., Khachigian, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+model+of+in-stent+restenosis:+rat+aortic+stenting.">A novel model of in-stent restenosis: rat aortic stenting.</a> Heart. 91, 393-395 (2005).</li><li>Marjamaa, J., 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=Occlusion+of+neck+remnant+in+experimental+rat+aneurysms+after+treatment+with+platinum-+or+polyglycolic-polylactic+acid-coated+coils.">Occlusion of neck remnant in experimental rat aneurysms after treatment with platinum- or polyglycolic-polylactic acid-coated coils.</a> Surg Neurol. 71, 458-465 (2009).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=with+the+support+of+the+NC3Rs.">with the support of the NC3Rs.</a> Aseptic Technique in Rodent Surgery. , (2014).</li><li>Bernal, J., 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=Guidelines+for+rodent+survival+surgery.">Guidelines for rodent survival surgery.</a> Journal of investigative surgery : the official journal of the Academy of Surgical Research. 22, 445-451 (2009).</li><li>Pritchett-Corning, K. R., Luo, Y., Mulder, G. B., White, W. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Principles+of+rodent+surgery+for+the+new.">Principles of rodent surgery for the new.</a> , (2011).</li><li>Marbacher, S., 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=Loss+of+mural+cells+leads+to+wall+degeneration,+aneurysm+growth,+and+eventual+rupture+in+a+rat+aneurysm+model.">Loss of mural cells leads to wall degeneration, aneurysm growth, and eventual rupture in a rat aneurysm model.</a> Stroke. 45, 248-254 (2014).</li><li>Frosen, J., 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=Remodeling+of+saccular+cerebral+artery+aneurysm+wall+is+associated+with+rupture:+histological+analysis+of+24+unruptured+and+42+ruptured+cases.">Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases.</a> Stroke. 35, 2287-2293 (2004).</li><li>Frosen, J., 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=Saccular+intracranial+aneurysm:+pathology+and+mechanisms.">Saccular intracranial aneurysm: pathology and mechanisms.</a> Acta neuropathologica. , 123-773 (2012).</li><li>Ysuda, R., Strother, C. M., Aagaard-Kienitz, B., Pulfer, K., Consigny, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+large+and+giant+bifurcation+aneurysm+model+in+canines:+proof+of+feasibility.">A large and giant bifurcation aneurysm model in canines: proof of feasibility.</a> AJNR Am J Neuroradiol. 33, 507-512 (2012).</li><li>Sherif, C., 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=Microsurgical+venous+pouch+arterial-bifurcation+aneurysms+in+the+rabbit+model:+technical+aspects.">Microsurgical venous pouch arterial-bifurcation aneurysms in the rabbit model: technical aspects.</a> Journal of visualized experiments : JoVE. , (2011).</li><li>Marjamaa, J., 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=High-resolution+TOF+MR+angiography+at+4.7+Tesla+for+volumetric+and+morphologic+evaluation+of+coiled+aneurysm+neck+remnants+in+a+rat+model.">High-resolution TOF MR angiography at 4.7 Tesla for volumetric and morphologic evaluation of coiled aneurysm neck remnants in a rat model.</a> Acta Radiol. 52, 340-348 (2011).</li></ol>

Авторы не имеют финансовый или коммерческий интерес в любом из препаратов, материалов, или используемого оборудования.

Прогресс в нашем понимании комплексной биологии саккулярной аневризмы мозговой артерии зависит от анализа эпидемиологических и клинических данных, дополненных лабораторных исследований на образцах пациентов и экспериментальных работ на животных моделях 3,12,13. ...

Разрыв саккулярной аневризмы мозговой артерии вызывает опасное для жизни кровотечение приводит к инсульту, постоянного неврологических повреждений или смерти. Разрыв может быть предотвращено либо микрохирургической отсечения или эндоваскулярного аневризмы окклюзии. Еще не было установлено медицинское лечение, чтобы предотвратить рост аневризмы и разрыва. Экспериментальные модели для мешотчатые аневризмы необходимы для изучения биологии артериальных аневризм и для тестирования новых терапевтических устройств и стратегий. Для этих целей, несколько различных моделей в различных видов были разработаны и опубликованы 1. Более крупные модели аневризмы в свиней, собак и кроликов предпочтительно использовать для проверки эндоваскулярных инновации в комплексном аневризмы архитектуры 1,2. Мышиные модели аневризмы, с другой стороны, позволяют тестирования исследовательские вопросы в генетически модифицированных видов 3,4 и облегчения разъяснения аневризмы биологии в Клеточная и молекулярнаяуровень гораздо лучше, чем крупных видов 1. Хотя эндоваскулярная транс-сонной и развертывание транс-подвздошной устройства ограничен больших крыс (&gt; 400-500 г) и стентов меньше, чем 2,0 мм и 1,5 мм в диаметре 5,6, стенты также могут быть размещены путем прямого введения в брюшной аорты сегмент укрывательство экспериментальные аневризмы. Предыдущая работа с использованием крысу микрохирургическая брюшной аорты боковины аневризма модели продемонстрировала свою целесообразность в тестирование новых эмболические устройств и его использование в изучении молекулярных основ аневризмы биологии 3,7. Многие из опубликованных в настоящее время экспериментальных мешотчатых моделей аневризмы требует дорогостоящего оборудования, специальных предприятиях (стерильные операционные номера с рентгеноскопии возможностей), интервенционной радиологии компетентность, или использование дорогих видов. Эти требования ограничивают широкое использование этих моделей, и привести к использованию различных моделей в разных лабораториях, которые мАКЕС сравнения данных и мета-анализ трудно, если не невозможно. Простой, надежный и недорогой экспериментальной модели необходим в качестве стандартизированного инструмента, который может быть использован в стандартизованной форме в различных лабораторий, чтобы получить сопоставимые результаты из разных учреждений. Для этого, мы создали аорты крысы боковины саккулярная артериальной аневризмы модель. Цель этого доклада заключается в представлении шаг за шагом процедурные инструкции, информацию о необходимой техникой, а также обсудить важные анатомические и хирургические характеристики для успешного микрохирургической создания брюшной аорты боковины аневризм у крыс.

<table border="0" cellpadding="0" cellspacing="0" width="752">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Name of Material/ Equipment</td>
			<td style="width:236px;">Company</td>
			<td style="width:119px;">Catalog Number</td>
			<td style="width:167px;">Comments/Description</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Medetomidine</td>
			<td style="width:236px;"></td>
			<td style="width:119px;"></td>
			<td>Any genericon</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Ketamin</td>
			<td style="width:236px;"></td>
			<td style="width:119px;"></td>
			<td>Any genericon</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Buprenorphine</td>
			<td style="width:236px;"></td>
			<td style="width:119px;"></td>
			<td>Any genericon</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Phosphate buffered saline</td>
			<td style="width:236px;"></td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Sodium dodecyl sulfate (0.1%)</td>
			<td style="width:236px;"></td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">3-0 resorbable suture</td>
			<td style="width:236px;">Ethicon Inc., USA</td>
			<td><a name="RANGE!C7">VCP824G</a></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">5-0 non absorbable suture</td>
			<td style="width:236px;">Ethicon Inc., USA</td>
			<td>8618G</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">6-0 non absorbable silk suture</td>
			<td style="width:236px;">B. Braun, Germany</td>
			<td style="width:119px;">C0761060</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">9-0 nylon micro suture</td>
			<td style="width:236px;">B. Braun, Germany</td>
			<td style="width:119px;">G1118471</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Spongostan</td>
			<td style="width:236px;">Ethicon Inc., USA</td>
			<td style="width:119px;">MS0002</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Operation microscope</td>
			<td style="width:236px;">Leica , Germany</td>
			<td style="width:119px;">M651</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Digital microscope camera</td>
			<td style="width:236px;">Sony, Japan</td>
			<td style="width:119px;">SSC-DC58AP</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Standard surgical instruments</td>
			<td style="width:236px;">B. Braun, Germany</td>
			<td style="width:119px;">Multiple</td>
			<td>See protocol 1.4</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Microsurgical instruments</td>
			<td style="width:236px;">B. Braun, Germany</td>
			<td style="width:119px;">Multiple</td>
			<td>See protocol 1.5</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Vascular clip applicator</td>
			<td style="width:236px;">B. Braun, Germany</td>
			<td style="width:119px;">FT495T</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">Temporary vascular clamps</td>
			<td style="width:236px;">B. Braun, Germany</td>
			<td style="width:119px;">FT250T</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;">Graph Pad Prism statistical software&#160;</td>
			<td style="width:236px;">GraphPad Software, San Diego, California, USA</td>
			<td style="width:119px;"></td>
			<td>V 6.02 for Windows</td>
		</tr>
	</tbody>
</table>

the helsinki rat microsurgical sidewall aneurysm model

Экспериментальные мешотчатых модели аневризмы необходимы для тестирования новых вариантов хирургического и эндоваскулярного лечения и устройств до их введения в клиническую практику. Кроме того, экспериментальные модели необходимы для выяснения сложного аневризмы биологию, ведущий к разрыву мешотчатые аневризмы. Несколько различных видов экспериментальных моделей для мешотчатые аневризмы были созданы в различных видов. Многие из них, однако, требует специальных навыков, дорогостоящего оборудования или специальных условий, что ограничивает их широкое применение. Простой, надежный и недорогой экспериментальной модели необходим в качестве стандартизированного инструмента, который может быть использован в стандартизованной форме в различных учреждениях. Микрохирургическая крысы в ​​животе модель аорты боковины аневризма сочетает в себе возможность учиться как новые стратегии эндоваскулярного лечения и молекулярную основу аневризмы биологии в стандартизированный и недорогойманера. Стандартные трансплантаты с помощью формы, размера и геометрии собирают из нисходящей грудной аорты крысы-донора, а затем пересадили в сингенной крысы-реципиента. Аневризмы ушивают конца в сторону с непрерывным или прерывается 9-0 нейлоновые швы, чтобы инфраренальной брюшной аорты. Мы представляем шаг за шагом процедурные инструкции, информацию о необходимой техникой, и обсудить важные анатомические и хирургические детали для успешного микрохирургической создания брюшной аорты боковины аневризмы у крыс.

Пилот серии включает 14 крыс. Впоследствии в общей сложности 84 животных были прооперированы по представленному протоколу для нескольких исследовательских проектов, в период с марта по сентябрь 2012 года Дополнительные 29 животных служили донорами для артериальных мешотчатых трансплант?...

Watch this Scientific Journal Video about The Helsinki Rat Microsurgical Sidewall Aneurysm Model at JoVE.com

The Helsinki Rat Microsurgical Sidewall Aneurysm Model

Microsurgical sidewall aneurysms in rats are created by end-to-side anastomosis of an aortic graft to the abdominal aorta. We present step-by-step instructions and discuss anatomical and surgical details for successful experimental saccular aneurysm creation.

Хельсинки Крыса микрохирургии Боковина Аневризма Модель

Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced ...

the-helsinki-rat-microsurgical-sidewall-aneurysm-model

Research

JoVE Journal

Medicine

12.1K Views.  University of Helsinki, Helsinki, Finland. Microsurgical sidewall aneurysms in rats are created by end-to-side anastomosis of an aortic graft to the abdominal aorta. We present step-by-step instructions and discuss anatomical and surgical details for successful experimental saccular aneurysm creation.

Video: The Helsinki Rat Microsurgical Sidewall Aneurysm Model

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.

Микрохирургическая Венозная Чехол Артериальная-Бифуркация Аневризмы в кролик Модель: Технические аспекты

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

A Model of Chronic Nutrient Infusion in the Rat

Chronic exposure to excessive levels of nutrients is postulated to affect the function of several organs and tissues and to contribute to the development of the many complications associated with obesity and the metabolic syndrome, including type 2 diabetes. To study the mechanisms by which excessive levels of glucose and fatty acids affect the pancreatic beta-cell and the secretion of insulin, we have established a chronic nutrient infusion model in the rat. The procedure consists of catheterizing the right jugular vein and left carotid artery under general anesthesia; allowing a 7-day recuperation period; connecting the catheters to the pumps using a swivel and counterweight system that enables the animal to move freely in the cage; and infusing glucose and/or Intralipid (a soybean oil emulsion which generates a mixture of approximately 80% unsaturated/20% saturated fatty acids when infused with heparin) for 72 hr. This model offers several advantages, including the possibility to finely modulate the target levels of circulating glucose and fatty acids; the option to co-infuse pharmacological compounds; and the relatively short time frame as opposed to dietary models. It can be used to examine the mechanisms of nutrient-induced dysfunction in a variety of organs and to test the effectiveness of drugs in this context.

A protocol for chronic infusions of glucose and Intralipid in rats is described. This model can be used to study the impact of nutrient excess on organ function and physiological parameters.

Модели хронического Питательные инфузии у крыс

Chronic exposure to excessive levels of nutrients is postulated to  affect the function of several organs and tissues and to contribute to the  ...

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.

Новый мышиной модели эндоваскулярной аневризмы аорты

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

The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat

Four to six week old, male Wistar rats were used to produce animal models of liver fibrosis. The process requires four weeks of administration of 10 mg/kg dimethylnitrosamine (DMN), given intraperitoneally for three consecutive days per week. Intraperitoneal injections were performed in the fume hood as DMN is a known hepatoxin and carcinogen. The model has several advantages. Firstly, liver changes can be studied sequentially or at particular stages of interest. Secondly, the stage of liver disease can be monitored by measurement of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes. Thirdly, the severity of liver damage at different stages can be confirmed by sacrifice of animals at designated time points, followed by histological examination of Masson&#39;s Trichome stained liver tissues. After four weeks of DMN dosing, the typical fibrosis score is 5 to 6 on the Ishak scale. The model can be reproduced consistently and has been widely used to assess the efficacy of potential anti-fibrotic agents.

We describe a method to produce an animal model of liver fibrosis in the rat, and assess the degree of fibrosis by histological examination of the liver. The model can be used to study the development of liver disease as well as to test the efficacy of potential anti-fibrotic agents.

Диметилнитрозамин Индуцированные печени Фиброз Модель в Rat

Four to six week old, male Wistar rats were used to produce animal models of liver fibrosis. The process requires four weeks of administration of 10 mg/kg ...

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.

Изометрические сократимости измерение верхней брыжеечной артерии мыши, с помощью проволоки миография

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

Corneal Epithelial Abrasion with Ocular Burr As a Model for Cornea Wound Healing

The murine cornea provides an excellent model to study wound healing. The cornea is the outermost layer of the eye, and thus is the first defense to injury. In fact, the most common type of eye injury found in clinic is a corneal abrasion. Here, we utilize an ocular burr to induce an abrasion resulting in removal of the corneal epithelium in vivo on anesthetized mice. This method allows for targeted and reproducible epithelial disruption, leaving other areas intact. In addition, we describe the visualization of the abraded epithelium with fluorescein staining and provide concrete advice on how to visualize the abraded cornea. Then, we follow the timeline of wound healing 0, 18, and 72 h after abrasion, until the wound is re-epithelialized. The epithelial abrasion model of corneal injury is ideal for studies on epithelial cell proliferation, migration and re-epithelialization of the corneal layers. However, this method is not optimal to study stromal activation during wound healing, because the ocular burr does not penetrate to the stromal cell layers. This method is also suitable for clinical applications, for example, pre-clinical test of drug effectiveness.

This protocol describes a method to inflict an abrasion to the ocular surface of the mouse, and to follow the wound healing process thereafter. The protocol takes advantage of an ocular burr to partially remove the surface epithelium of the eye in anaesthetized mice.

Роговицы эпителиальных истиранию с глазной заусенцев, как модель для роговицы заживление ран

The murine cornea provides an excellent model to study wound healing. The cornea is the outermost layer of the eye, and thus is the first defense to ...

An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and one of the leading causes of blindness in working-age adults. No current animal models of diabetes and oxygen-induced retinopathy develop the full-range progressive changes manifested in human proliferative diabetic retinopathy (PDR). Therefore, understanding of the disease pathogenesis and pathophysiology has relied largely on the use of histological sections and vitreous samples in approaches that only provide steady-state information on the involved pathogenic factors. Increasing evidence indicates that dynamic cell-cell and cell-extracellular matrix (ECM) interactions in the context of three-dimensional (3D) microenvironments are essential for the mechanistic and functional studies towards the development of new treatment strategies. Therefore, we hypothesized that the pathological fibrovascular tissue surgically excised from eyes with PDR could be utilized to reliably unravel the cellular and molecular mechanisms of this devastating disease and to test the potential for novel clinical interventions. Towards this end, we developed a novel method for 3D ex vivo culture of surgically-excised patient-derived fibrovascular tissue (FT), which will serve as a relevant model of human PDR pathophysiology. The FTs are dissected into explants and embedded in fibrin matrix for ex vivo culture and 3D characterization. Whole-mount immunofluorescence of the native FTs and end-point cultures allows thorough investigation of tissue composition and multicellular processes, highlighting the importance of 3D tissue-level characterization for uncovering relevant features of PDR pathophysiology. This model will allow the simultaneous assessment of molecular mechanisms, cellular/tissue processes and treatment responses in the complex context of dynamic biochemical and physical interactions within the PDR tissue architecture and microenvironment. Since this model recapitulates PDR pathophysiology, it will also be amenable for testing or developing new treatments.

Here, we present a protocol to study the pathophysiology of proliferative diabetic retinopathy by using patient-derived, surgically-excised, fibrovascular tissues for three-dimensional native tissue characterization and ex vivo culture. This ex vivo culture model is also amenable for testing or developing new treatments.

Культура ткани модель Ex Vivo сортопопуляциях осложнений в пролиферативной диабетической ретинопатии

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and one of the leading causes of blindness in working-age adults. No ...

Murine Surgical Model of Topical Elastase Induced Descending Thoracic Aortic Aneurysm

According to the Center for Disease Control, aortic aneurysms (AAs) were considered a leading cause of death in all races and both sexes from 1999-2016. An aneurysm forms as a result of progressive weakening and eventual dilation of the aorta, which can rupture or tear once it reaches a critical diameter. Aneurysms of the descending aorta in the chest, called descending thoracic aortic aneurysms (dTAA), make up a large proportion of aneurysm cases in the United States. Uncontained dTAA rupture is almost universally lethal, and elective repair has a high rate of morbidity and mortality. The purpose of our model is to study dTAA specifically, to elucidate the pathophysiology of dTAA and to search for molecular targets to halt the growth or reduce the size of dTAA. By having a murine model to study thoracic pathology precisely, targeted therapies can be developed to specifically test dTAA. The method is based on the placement of porcine pancreatic elastase (PPE) directly on the outer murine aortic wall after surgical exposure. This creates a destructive and inflammatory reaction, which weakens the aortic wall and allows for aneurysm formation over weeks to months. Though murine models possess limitations, our dTAA model produces robust aneurysms of predictable size. Furthermore, this model can be used to test genetic and pharmaceutical targets which may arrest dTAA growth or prevent rupture. In human patients, interventions such as these could help avoid aneurysm rupture, and difficult surgical intervention.

We describe a surgical protocol to consistently induce robust descending thoracic aortic aneurysms in mice. The procedure involves left thoracotomy, thoracic aorta exposure, and placement of a sponge soaked in porcine pancreatic elastase on the aortic wall.

Murine Хирургическая модель Томатная Эластаза индуцированной спуск торакальной аортальной аневризмы

According to the Center for Disease Control, aortic aneurysms (AAs) were considered a leading cause of death in all races and both sexes from 1999-2016. ...

Porcine Model of Infrarenal Abdominal Aortic Aneurysm

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called &#946;-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease.
Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone.
Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% &#177; 47.4% at day 7, 105.4% &#177; 58.1% at day 14, and 113.5% &#177; 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p &#60; 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease.
Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.&#160;

This novel model creates robust infrarenal abdominal aortic aneurysms in swine using a combination of balloon angioplasty, elastase/collagenase perfusion, topical elastase application, and oral compound &#946;-aminopropionitrile administration, which interferes with collagen cross-linking.

Свиная модель инфрагенной абдоминальной аневризмы аорты

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal ...

Vessel-Sparing Microsurgical Longitudinal Intussusception Vasoepididymostomy to Treat Epididymal Obstructive Azoospermia

The epididymis is a common site of obstruction in obstructive azoospermia (OA). Vasoepididymostomy has become an important method for the treatment of epididymal OA since 2000. There are two challenges in classic microscopic vasoepididymostomy. First, anastomosis of the vas deferens and epididymis is performed with double-needle sutures. However, there is a lack of good-quality and cost-effective double-needle sutures in China, which leads to increased difficulty and poor success rates of anastomosis. Second, the separation of the vas deferens does not retain vasculature, although the vas deferens vasculature plays an important role in the blood supply to the vas deferens, epididymis, and testis. This affects the blood supply to the anastomotic area and epididymis.
Therefore, this team has made innovative improvements to address these problems. Good-quality, cost-effective, single-needle sutures, which are easy to purchase in China and other countries, were used in microsurgical longitudinal intussusception vasoepididymostomy. This can optimize the operation procedure and shorten the operation time while ensuring the success rate of the anastomosis. The surgical method of preserving the vas deferens vessels was innovatively proposed because the etiology of epididymal OA is mostly inflammatory in China. The protection of the blood supply to the vas deferens and epididymis is maximized using microsurgical forceps to separate and protect the vasculature. Patency reached 81.7% in the postoperative follow-up, indicating a better surgical treatment effect.

The present protocol describes a vessel-sparing, longitudinal intussusception vasoepididymostomy using readily available single-needle sutures in China, a safe and effective procedure, which may improve patients' patency and natural pregnancy rates.

Сосудосберегающая микрохирургическая продольная инвагинация кишечника Вазоэпидидимостомия для лечения эпидидимально-обструктивной азооспермии

The epididymis is a common site of obstruction in obstructive azoospermia (OA). Vasoepididymostomy has become an important method for the treatment of ...