Name: vascular balloon injury and intraluminal administration in rat carotid artery
Uploaded: 2014-12-23T13:00:00
Description: Watch this Scientific Journal Video about Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery at JoVE.com

We are grateful to Dr. Clowes for first developing and describing this method. We are also thankful to Dr. Tulis for his detailed protocol which has been fundamentally helpful to our previous, current and future work. This work was supported by grants R01HL097111 and R01HL123364 from the NIH to M.T., and by American Heart Association grant 14GRNT18880008 to M.T.
We would like to thank Rachel Newton for her expert technical support and for her valuable help during the filming process.

NOTE: L&#39;utilisation d&#39;animaux pour les expériences suivantes a été examiné et approuvé par le Comité des soins et de l&#39;utilisation des animaux institutionnel (IACUC). 1. Procédures préopératoires <ol style="margin-left: 40px;"><li> Stériliser les instruments chirurgicaux avant utilisation. <ol><li> Autoclave tous les instruments chirurgicaux 24 heures ou moins avant la chirurgie. Si de multiples interventions chirurgicales sont effectuées le même jour, stériliser les instruments par un...

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	<li>Landzberg, B. R., Frishman, W. H., Lerrick, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathophysiology+and+pharmacological+approaches+for+prevention+of+coronary+artery+restenosis+following+coronary+artery+balloon+angioplasty+and+related+procedures.">Pathophysiology and pharmacological approaches for prevention of coronary artery restenosis following coronary artery balloon angioplasty and related procedures.</a> Progress in Cardiovascular Diseases. 39, 361-398 (1997).</li><li>Muller, D. W., Ellis, S. G., Topol, E. J. <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+coronary+artery+restenosis.">Experimental models of coronary artery restenosis.</a> J. Am. Coll. Cardiol. 19, 418-432 (1992).</li><li>Clowes, A. W., Reidy, M. A., Clowes, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinetics+of+cellular+proliferation+after+arterial+injury.+I.+Smooth+muscle+growth+in+the+absence+of+endothelium.">Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium.</a> Laboratory Investigation: A Journal of Technical Methods and Pathology. 49, 327-333 (1983).</li><li>Clowes, A. W., Reidy, M. A., Clowes, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+of+stenosis+after+arterial+injury.">Mechanisms of stenosis after arterial injury.</a> Laboratory Investigation: A Journal of Technical Methods and Pathology. 49, 208-215 (1983).</li><li>Clowes, A. W., Clowes, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinetics+of+cellular+proliferation+after+arterial+injury.+IV.+Heparin+inhibits+rat+smooth+muscle+mitogenesis+and+migration.">Kinetics of cellular proliferation after arterial injury. IV. Heparin inhibits rat smooth muscle mitogenesis and migration.</a> Circulation Research. 58, 839-845 (1986).</li><li>Li, G., Chen, S. J., Oparil, S., Chen, Y. F., Thompson, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+in+vivo+evidence+demonstrating+neointimal+migration+of+adventitial+fibroblasts+after+balloon+injury+of+rat+carotid+arteries.">Direct in vivo evidence demonstrating neointimal migration of adventitial fibroblasts after balloon injury of rat carotid arteries.</a> Circulation. 101, 1362-1365 (2000).</li><li>Kiechl, S., Willeit, 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+natural+course+of+atherosclerosis.+Part+II:+vascular+remodeling.">The natural course of atherosclerosis. Part II: vascular remodeling.</a> Bruneck Study Group. Arteriosclerosis, Thrombosis, and Vascular Biology. 19, 1491-1498 (1999).</li><li>Yamamoto, 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=Derivation+of+rat+embryonic+stem+cells+and+generation+of+protease-activated+receptor-2+knockout+rats.">Derivation of rat embryonic stem cells and generation of protease-activated receptor-2 knockout rats.</a> Transgenic Research. 21, 743-755 (2012).</li><li>Intengan, H. D., Schiffrin, E. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vascular+remodeling+in+hypertension:+roles+of+apoptosis,+inflammation,+and+fibrosis.">Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis.</a> Hypertension. 38, 581-587 (2001).</li><li>Meng, H., 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+hemodynamics+at+the+apex+of+an+arterial+bifurcation+induces+vascular+remodeling+resembling+cerebral+aneurysm+initiation.">Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation.</a> Stroke. 38, 1924-1931 (2007).</li><li>Sun, C. K., Shao, P. L., Wang, C. J., Yip, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Study+of+vascular+injuries+using+endothelial+denudation+model+and+the+therapeutic+application+of+shock+wave:+a+review.">Study of vascular injuries using endothelial denudation model and the therapeutic application of shock wave: a review.</a> American Journal of Rranslational Research. 3, 259-268 (2011).</li><li>Zhang, W., 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=Orai1-mediated+I+(CRAC)+is+essential+for+neointima+formation+after+vascular+injury.">Orai1-mediated I (CRAC) is essential for neointima formation after vascular injury.</a> Circulation Research. 109, 534-542 (2011).</li><li>Ollinger, R., 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=Bilirubin:+a+natural+inhibitor+of+vascular+smooth+muscle+cell+proliferation.">Bilirubin: a natural inhibitor of vascular smooth muscle cell proliferation.</a> Circulation. 112, 1030-1039 (2005).</li><li>Levitzki, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PDGF+receptor+kinase+inhibitors+for+the+treatment+of+restenosis.">PDGF receptor kinase inhibitors for the treatment of restenosis.</a> Cardiovascular Research. 65, 581-586 (2005).</li><li>Asahara, 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=Local+delivery+of+vascular+endothelial+growth+factor+accelerates+reendothelialization+and+attenuates+intimal+hyperplasia+in+balloon-injured+rat+carotid+artery.">Local delivery of vascular endothelial growth factor accelerates reendothelialization and attenuates intimal hyperplasia in balloon-injured rat carotid artery.</a> Circulation. 91, 2793-2801 (1995).</li><li>Lee, K. 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=Alpha-lipoic+acid+inhibits+fractalkine+expression+and+prevents+neointimal+hyperplasia+after+balloon+injury+in+rat+carotid+artery.">Alpha-lipoic acid inhibits fractalkine expression and prevents neointimal hyperplasia after balloon injury in rat carotid artery.</a> Atherosclerosis. 189, 106-114 (2006).</li><li>Ji, R., 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=MicroRNA+expression+signature+and+antisense-mediated+depletion+reveal+an+essential+role+of+MicroRNA+in+vascular+neointimal+lesion+formation.">MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation.</a> Circulation Research. 100, 1579-1588 (2007).</li><li>Merlet, E., 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=miR-424/322+regulates+vascular+smooth+muscle+cell+phenotype+and+neointimal+formation+in+the+rat.">miR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat.</a> Cardiovascular Research. 98, 458-468 (2013).</li><li>Huang, J., Niu, X. L., Pippen, A. M., Annex, B. H., Kontos, C. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adenovirus-mediated+intraarterial+delivery+of+PTEN+inhibits+neointimal+hyperplasia.">Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia.</a> Arteriosclerosis, Thrombosis, And Vascular Biology. 25, 354-358 (2005).</li><li>Gonzalez-Cobos, J. 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=Store-independent+Orai1/3+channels+activated+by+intracrine+leukotriene+C4:+role+in+neointimal+hyperplasia.">Store-independent Orai1/3 channels activated by intracrine leukotriene C4: role in neointimal hyperplasia.</a> Circulation Research. 112, 1013-1025 (2013).</li><li>Guzman, L. A., 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=Local+intraluminal+infusion+of+biodegradable+polymeric+nanoparticles.+A+novel+approach+for+prolonged+drug+delivery+after+balloon+angioplasty.">Local intraluminal infusion of biodegradable polymeric nanoparticles. A novel approach for prolonged drug delivery after balloon angioplasty.</a> Circulation. 94, 1441-1448 (1996).</li><li>Lipke, E. A., West, J. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Localized+delivery+of+nitric+oxide+from+hydrogels+inhibits+neointima+formation+in+a+rat+carotid+balloon+injury+model.">Localized delivery of nitric oxide from hydrogels inhibits neointima formation in a rat carotid balloon injury model.</a> Acta Biomaterialia. 1, 597-606 (2005).</li><li>Osterrieder, W., 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=Role+of+angiotensin+II+in+injury-induced+neointima+formation+in+rats.">Role of angiotensin II in injury-induced neointima formation in rats.</a> Hypertension. 18, II60-II64 (1991).</li><li>Powell, J. 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=Inhibitors+of+angiotensin-converting+enzyme+prevent+myointimal+proliferation+after+vascular+injury.">Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury.</a> Science. 245, 186-188 (1989).</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=Does+the+new+angiotensin+converting+enzyme+inhibitor+cilazapril+prevent+restenosis+after+percutaneous+transluminal+coronary+angioplasty?+Results+of+the+MERCATOR+study:+a+multicenter,+randomized,+double-blind+placebo-controlled+trial.+Multicenter+European+Research+Trial+with+Cilazapril+after+Angioplasty+to+Prevent+Transluminal+Coronary+Obstruction+and+Restenosis+(MERCATOR)+Study+Group.">Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary angioplasty? Results of the MERCATOR study: a multicenter, randomized, double-blind placebo-controlled trial. Multicenter European Research Trial with Cilazapril after Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis (MERCATOR) Study Group.</a> Circulation. 86, 100-110 (1992).</li><li>Faxon, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+high+dose+angiotensin-converting+enzyme+inhibition+on+restenosis:+final+results+of+the+MARCATOR+Study,+a+multicenter,+double-blind,+placebo-controlled+trial+of+cilazapril.">Effect of high dose angiotensin-converting enzyme inhibition on restenosis: final results of the MARCATOR Study, a multicenter, double-blind, placebo-controlled trial of cilazapril.</a> The Multicenter American Research Trial With Cilazapril After Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis (MARCATOR) Study Group. J Am Coll Cardiol. 25, 362-369 (1995).</li><li>Geurts, A. 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=Knockout+rats+via+embryo+microinjection+of+zinc-finger+nucleases.">Knockout rats via embryo microinjection of zinc-finger nucleases.</a> Science. 325, 433 (2009).</li><li>Tesson, L., 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=Knockout+rats+generated+by+embryo+microinjection+of+TALENs.">Knockout rats generated by embryo microinjection of TALENs.</a> Nature Biotechnology. 29, 695-696 (2011).</li><li>Li, D., 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=Heritable+gene+targeting+in+the+mouse+and+rat+using+a+CRISPR-Cas+system.">Heritable gene targeting in the mouse and rat using a CRISPR-Cas system.</a> Nature Biotechnology. 31, 681-683 (2013).</li><li>Potier, 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=Evidence+for+STIM1-+and+Orai1-dependent+store-operated+calcium+influx+through+ICRAC+in+vascular+smooth+muscle+cells:+role+in+proliferation+and+migration.">Evidence for STIM1- and Orai1-dependent store-operated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration.</a> FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology. 23, 2425-2437 (2009).</li><li>Aubart, F. 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=RNA+interference+targeting+STIM1+suppresses+vascular+smooth+muscle+cell+proliferation+and+neointima+formation+in+the+rat.+Molecular+Therapy.">RNA interference targeting STIM1 suppresses vascular smooth muscle cell proliferation and neointima formation in the rat. Molecular Therapy.</a> The Journal Of The American Society Of Gene Therapy. 17, 455-462 (2009).</li><li>Berra-Romani, R., Mazzocco-Spezzia, A., Pulina, M. V., Golovina, V. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ca2++handling+is+altered+when+arterial+myocytes+progress+from+a+contractile+to+a+proliferative+phenotype+in+culture.+American+journal+of+physiology.">Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture. American journal of physiology.</a> Cell Physiology. 295, C779-C790 (2008).</li><li>Bisaillon, J. 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=Essential+role+for+STIM1/Orai1-mediated+calcium+influx+in+PDGF-induced+smooth+muscle+migration.+American+journal+of+physiology.">Essential role for STIM1/Orai1-mediated calcium influx in PDGF-induced smooth muscle migration. American journal of physiology.</a> Cell Physiology. 298, C993-C1005 (2010).</li><li>Tulis, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rat+carotid+artery+balloon+injury+model.">Rat carotid artery balloon injury model.</a> Methods In Molecular Medicine. 139, 1-30 (2007).</li><li>Zhang, W., Trebak, M., Szallasi, A., B&#237;r&#243;, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Balloon+Injury+in+Rats+as+a+Model+for+Studying+TRP+Channel+Contribution+to+Vascular+Smooth+Muscle+Remodeling.">Balloon Injury in Rats as a Model for Studying TRP Channel Contribution to Vascular Smooth Muscle Remodeling.</a> T TRP Channels in Drug DiscoveryMethods in Pharmacology and Toxicology. , 101-111 (2012).</li><li>Tulis, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Histological+and+morphometric+analyses+for+rat+carotid+balloon+injury+model).">Histological and morphometric analyses for rat carotid balloon injury model).</a> Methods In Molecular Medicine. 139, 31-66 (2007).</li></ol>

La blessure carotide ballon de rat a été bien décrit par Tulis en 2007 34. Il a été entièrement discuté tous les détails de cette procédure par le Dr Tulis. Les lecteurs qui se intéressent à cette procédure sont fortement recommandés pour lire le protocole de Tulis. Cependant, il ya une chose que nous ne sommes pas d&#39;accord avec le Dr Tulis: Au lieu de gonfler le ballon avec une solution saline ou un autre type de liquide, nous avons proposé à gonfler avec de l&#39;air. Selon notre expérience personnelle, gonf...

Les cathéters à ballonnet sont des dispositifs médicaux utilisés dans le mode opératoire de l&#39;angioplastie, dans le but d&#39;élargir site (s) obstruée de l&#39;athérome ou d&#39;un thrombus dans un vaisseau sanguin. La lumière de vaisseau rétréci est forcé à ouvrir par le ballon gonflé et l&#39;approvisionnement en sang seraient restaurées de manière séquentielle pour soulager les symptômes d&#39;ischémie en aval, tels que l&#39;angine de poitrine, infarctus du myocarde, et la douleur de la jambe. Néanmoins, le grand succès de l&#39;angioplastie a été diminué de complications post-opératoires telles que les résultats de la force causant barotraumatisme vasculaire (lésion par ballonnet), à savoir paroi du vaisseau remodelage et dans de nombreux cas, une nouvelle rétrécissement de la lumière des vaisseaux (resténose) 1. Un certain nombre de modèles animaux ont été développés imitant la procédure d&#39;angioplastie pour aider les enquêteurs à comprendre les mécanismes qui sous-tendent le navire mur remodelage liés à ballonnet 2 blessures. Parmi toutes les espèces d&#39;animaux utilisés pour la modélisation, le rat est le plus fréquemment utilisé. Car rapport aux lapins, les chiens et les porcs, les avantages de rats sont leur faible coût, leur relative facilité d&#39;utilisation et les connaissances actuelles de la physiologie du rat. Bien que les souris ont un avantage supplémentaire dans une large gamme de souches manipulées génétiquement, le récipient de souris est trop petite pour insérer un cathéter à ballonnet. Au cours des trois dernières décennies, les rats expérimentaux ont permis aux chercheurs d&#39;acquérir une meilleure compréhension des mécanismes moléculaires et cellulaires qui sous-tendent la formation de néo-intima et le remodelage vasculaire 3-6. Au-delà de la lésion par ballonnet, le remodelage vasculaire sont également impliqués dans la plupart des maladies vasculaires majeurs, tels que l&#39;athérosclérose 7,8, l&#39;hypertension 9 et 10 anévrisme. Ainsi, les connaissances acquises par le modèle de blessure par ballon est en général bénéfique pour les études globales de la maladie de la paroi vasculaire. L&#39;objectif global du modèle de lésion par ballonnet de rat ne est pas seulement pour mieux comprendre les maladies vasculaires mais aussi de tester la puissance de nouveaux agents pourcontrôle de la maladie 11,12. Traitement de la toxicomanie à la resténose clinique actuelle est appliquée par les stents à élution médicamenteuse passées via la lumière du vaisseau juste après angioplastie. Dans les modèles animaux, d&#39;une manière encore plus économique efficace pour les essais de l&#39;agent nouveau, ce est une méthode bien développé perfusion intraluminale locale. Les agents candidats qui ont été testés grâce à cette méthode comprennent les médicaments à petites molécules 13,14, cytokines ou des facteurs de croissance 15,16, Gene manipulation agents (clones d&#39;ADNc, siRNA, etc.) 17-20, et de nouvelles formulations pharmaceutiques 21,22. Jusqu&#39;à présent, le ballon modèle de lésion de rat reste l&#39;un des modèles les plus utiles pour l&#39;étude des maladies vasculaires / troubles. Ce est l&#39;étape fondamentale du laboratoire au chevet du patient, généralement comme la première étape de déplacement in vitro in vivo, mais il ne devrait pas être la dernière. Le résultat d&#39;expériences de rat doit être délibéré et caractérisé en outre avant la traduction en humainel&#39;utilisation clinique, en raison de la différence dans les lits vasculaires et anatomie navire ainsi que les différences entre les espèces intrinsèques humain et de rat 23-26. Néanmoins, il est encore un outil essentiel dans la recherche médicale translationnelle. Bien que cette recherche a utilisé être limitée par le manque de rats génétiquement modifiés, il n&#39;a plus été un problème car de nouvelles approches génomiques tels que le zinc-nucléases doigt 27, 28 et TALENs CRISPR-Cas 29 ont fait rats knockout facilement accessible.

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			<td height="21" style="height:21px;width:384px;">Name of Material/ Equipment</td>
			<td style="width:389px;">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;">Fogarty balloon embolectomy catheters, 2 French&#160;</td>
			<td>Edwards Lifesciences, Germany</td>
			<td>&#160;120602F</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Deltaphase Operating Board - Includes 2 Pads &#38; 2 Insulators</td>
			<td>Braintree Scientific, Inc.</td>
			<td>39OP</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">&#160;LED light source</td>
			<td>Fisher Scientific</td>
			<td>12-563-501&#160;</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Hartmann Mosquito Forceps 4&#8221; curved</td>
			<td>Apiary Medical, Inc. San Diego, CA</td>
			<td>gS 22.1670</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Crile Retractor 4&#8221; double ended</td>
			<td>Apiary Medical, Inc.</td>
			<td>gS 34.1934</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Other surgical instruments</td>
			<td>Roboz Surgical Instrument Company, Inc., Gaithersburg, MD</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Peripheral Intravenous (I.V.) Cannula, 24G</td>
			<td>BD</td>
			<td>381312</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Ketamine HCl, 100mg/mL, 10mL</td>
			<td>Ketaset- Patterson Vet</td>
			<td>07-803-6637&#160;</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Xylazine (AnaSed),20mg/mL,20mL</td>
			<td>Ketaset- Patterson Vet</td>
			<td>07-808-1947</td>
			<td></td>
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vascular balloon injury and intraluminal administration in rat carotid artery

Le ballon modèle de lésion de l&#39;artère carotide chez le rat a été bien établie depuis plus de deux décennies. Il reste un moyen important d&#39;étudier les mécanismes moléculaires et cellulaires impliqués dans la dédifférenciation vasculaire du muscle lisse, la formation de néo-intima et le remodelage vasculaire. Des rats Sprague-Dawley sont les animaux les plus fréquemment employé pour ce modèle. Des rats femelles ne sont pas préférés comme des hormones féminines sont de protection contre les maladies vasculaires et donc introduisent une variation dans cette procédure. La carotide gauche est généralement blessé à la carotide droite servant de témoin négatif. Lésion de la carotide gauche est causée par le ballonnet gonflé qui dénude l&#39;endothélium et s distendre la paroi du vaisseau. Après une lésion, les stratégies thérapeutiques potentielles telles que l&#39;utilisation de composés pharmacologiques et soit gène ou transfert shRNA peuvent être évalués. Typiquement pour le gène ou le transfert shRNA, la section blessés de la lumière du vaisseau est transduit localement pour 30 min avec vparticules Iral codant soit une protéine ou un shRNA pour la livraison et l&#39;expression dans la paroi du vaisseau blessé. Épaississement néo-intimale représentant cellules prolifératives des muscles lisses vasculaires pics habituellement à 2 semaines après la lésion. Les navires sont souvent récoltées à ce point de temps pour l&#39;analyse cellulaire et moléculaire des voies de signalisation cellulaire ainsi que le gène et l&#39;expression des protéines. Les bateaux peuvent également être récoltées à des moments antérieurs afin de déterminer l&#39;apparition de l&#39;expression et / ou l&#39;activation d&#39;une protéine ou d&#39;une voie spécifique, en fonction des objectifs expérimentaux destinés. Les navires peuvent être caractérisés et évalués en utilisant une coloration histologique, immunohistochimie, les dosages de protéine / ARNm, et des dosages d&#39;activité. La intacte l&#39;artère carotide droite du même animal est un contrôle interne idéal. Les changements induits blessures dans les paramètres moléculaires et cellulaires peuvent être évaluées en comparant l&#39;artère blessés vers la droite artère de contrôle interne. De même, les modalités thérapeutiques peuvent être évalués en comparant le blesserd et traités artère pour le contrôle blessé ne artère.

Deux semaines après la blessure, les artères carotides sont récoltées, sectionnées et soumises à l&#39;analyse morphologique. Les artères sont en coupe transversale et colorées avec H &amp; E (figures 1, 2B, C et 3). Paroi de l&#39;artère carotide Rat contient quatre couches de lame élastique, qui apparaissent comme des lignes roses. La zone comprise entre la strate extérieure, lamina élastique externe (EEL) et de la lame la plus intérieure, la lamina élastique interne (IEL) est le média ...

Watch this Scientific Journal Video about Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery at JoVE.com

Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery

Ce protocole utilise un cathéter à ballonnet pour provoquer une blessure sur intraluminale de l&#39;artère carotide de rat et désormais provoquer une hyperplasie néo-intimale. Ce est un modèle bien établi pour étudier les mécanismes de remodelage vasculaire en réponse à une lésion. Il est également largement utilisé pour déterminer la validité des approches thérapeutiques potentielles.

Vasculaire Balloon blessures et de l&#39;administration chez le rat Intraluminal artère carotide

The carotid artery balloon injury model in rats has been well established for over two decades. It remains an important method to study the molecular and ...

vascular-balloon-injury-intraluminal-administration-rat-carotid

Research

JoVE Journal

Medicine

Training a Sophisticated Microsurgical Technique: Interposition of External Jugular Vein Graft in the Common Carotid Artery in Rats

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in peripheral arterial bypass surgery as well as in arteriovenous fistulas.1-5 The experimental procedure of vein graft interposition in the common carotid artery by using the cuff-technique has been applied in several research projects to examine the aetiology of neointimal hyperplasia and therapeutic options to address it. 6-8 The cuff prevents vessel anastomotic remodeling and induces turbulence within the graft and thereby the development of neointimal hyperplasia.
Using the superior caval vein graft is an established small-animal model for venous arterialization experiment.9-11 This current protocol refers to an established jugular vein graft interposition technique first described by Zou et al., 9 as well as others.12-14 Nevertheless, these cited small animal protocols are complicated.
To simplify the procedure and to minimize the number of experimental animals needed, a detailed operation protocol by video training is presented. This video should help the novice surgeon to learn both the cuff-technique and the vein graft interposition. Hereby, the right external jugular vein was grafted in cuff-technique in the common carotid artery of 21 female Sprague Dawley rats categorized in three equal groups that were sacrificed on day 21, 42 and 84, respectively. Notably, no donor animals were needed, because auto-transplantations were performed. The survival rate was 100 % at the time point of sacrifice. In addition, the graft patency rate was 60 % for the first 10 operated animals and 82 % for the remaining 11 animals. The blood flow at the time of sacrifice was 8&plusmn;3 ml/min. In conclusion, this surgical protocol considerably simplifies, optimizes and standardizes this complicated procedure. It gives novice surgeons easy, step-by-step instruction, explaining possible pitfalls, thereby helping them to gain expertise fast and avoid useless sacrifice of experimental animals.

Neointimal hyperplasia is the primary cause of stenosis in arterialized veins. We propose a new protocol whereby the right external jugular vein is grafted using the cuff technique in the common carotid artery of Sprague Dawley rats. The survival rate was 100 % at the time point of sacrifice.

Former une technique microchirurgicale sophistiquée: Interposition de greffe veine jugulaire externe dans l&#39;artère carotide commune chez les rats

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in ...

Recherche

Médecine

Optimized System for Cerebral Perfusion Monitoring in the Rat Stroke Model of Intraluminal Middle Cerebral Artery Occlusion

The translational potential of pre-clinical stroke research depends on the accuracy of experimental modeling. Cerebral perfusion monitoring in animal models of acute ischemic stroke allows to confirm successful arterial occlusion and exclude subarachnoid hemorrhage. Cerebral perfusion monitoring can also be used to study intracranial collateral circulation, which is emerging as a powerful determinant of stroke outcome and a possible therapeutic target. Despite a recognized role of Laser Doppler perfusion monitoring as part of the current guidelines for experimental cerebral ischemia, a number of technical difficulties exist that limit its widespread use. One of the major issues is obtaining a secure and prolonged attachment of a deep-penetration Laser Doppler probe to the animal skull. In this video, we show our optimized system for cerebral perfusion monitoring during transient middle cerebral artery occlusion by intraluminal filament in the rat. We developed in-house a simple method to obtain a custom made holder for twin-fibre (deep-penetration) Laser Doppler probes, which allow multi-site monitoring if needed. A continuous and prolonged monitoring of cerebral perfusion could easily be obtained over the intact skull.

Cerebral perfusion monitoring has been demonstrated to improve accuracy in ischemic stroke models. Technical difficulties often limit the use of this essential tool for cerebrovascular research. In this video, an optimized system is shown to obtain a single or multi-site hemodynamic monitoring during intraluminal middle cerebral artery occlusion in rats.

Système optimisé pour la surveillance de la perfusion cérébrale chez le rat des maladies du intraluminale occlusion de l&#39;artère cérébrale moyenne

The translational potential of pre-clinical stroke research depends on the accuracy of experimental modeling. Cerebral perfusion monitoring in animal ...

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study model. As the use of mouse models are often a vital step in preclinical drug discovery and drug development1-8, it is necessary to design a system to introduce drugs into mice in a uniform, reproducible manner. Ideally, the system should permit the collection of blood samples at regular intervals over a set time course. The ability to measure drug concentrations by mass-spectrometry, has allowed investigators to follow the changes in plasma drug levels over time in individual mice1, 9, 10. In this study, paclitaxel was introduced into transgenic mice as a continuous arterial infusion over three hours, while blood samples were simultaneously taken by retro-orbital bleeds at set time points. Carotid artery infusions are a potential alternative to jugular vein infusions, when factors such as mammary tumors or other obstructions make jugular infusions impractical. Using this technique, paclitaxel concentrations in plasma and tissue achieved similar levels as compared to jugular infusion. In this tutorial, we will demonstrate how to successfully catheterize the carotid artery by preparing an optimized catheter for the individual mouse model, then show how to insert and secure the catheter into the mouse carotid artery, thread the end of the catheter out through the back of the mouse&#8217;s neck, and hook the mouse to a pump to deliver a controlled rate of drug influx. Multiple low volume retro-orbital bleeds allow for analysis of plasma drug concentrations over time.

This method was developed with the goal of delivering a steady drug solution via the carotid artery, to assess the pharmacokinetics of novel drugs in mouse models.

Infusions de l&#39;artère carotide pour pharmacocinétiques et pharmacodynamiques Analyse des taxanes chez la souris

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

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

Severe thrombosis and its ischemic consequences such as myocardial infarction, pulmonary embolism and stroke are major worldwide health issues. The ferric chloride injury is now a well-established technique to rapidly and accurately induce the formation of thrombi in exposed veins or artery of small and large diameter. This model has played a key role in the study of the pathophysiology of thrombosis, in the discovery and validation of novel antithrombotic drugs and in the understanding of the mechanism of action of these new agents. Here, the implementation of this technique on a mesenteric vessel and carotid artery in mice is presented. The method describes how to label circulating leukocytes and platelets with a fluorescent dye and to observe, by intravital microscopy on the exposed mesentery, their accumulation at the injured vessel wall which leads to the formation of a thrombus. On the carotid artery, the occlusion caused by the clot formation is measured by monitoring the blood flow with a Doppler probe.

The FeCl3 induced thrombosis model in mice is described herein. A method to monitor thrombus growth by intravital microscopy observation on a mesenteric vessel and by blood flow measurement in the carotid artery is presented.

Chlorure ferrique induite souris thrombose type sur l&#39;artère carotide et Mesentery navire

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

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

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is also a valuable model system to test, and to evaluate therapeutics and drugs that negate maladaptive remodeling in the vessel. The injury, or barotrauma, in the vessel lumen caused by an inflated balloon via an inserted catheter induces subsequent neointimal growth, often leading to hyperplasia or thickening of the vessel wall that narrows, or obstructs the lumen. The method described here is sufficiently sensitive, and the results can be obtained in relatively short time (2 weeks after the surgery). The efficacy of the drug or therapeutic against the induced-remodeling can be evaluated either by the post-mortem pathological and histomorphological analysis, or by ultrasound sonography in live animals. In addition, this model system has also been used to determine the therapeutic window or the time course of the administered drug. These studies can leadto the development of a better administrative strategy and a better therapeutic outcome. The procedure described here provides a tool for translational studies that bring drug and therapeutic candidates from bench research to clinical applications.

The rat carotid balloon injury model described below allows researchers to evaluate drugs or therapeutics that negate injury-induced arterial hyperplasia. Detailed pre-surgical preparation, surgical procedure, and post-surgical cares of the animal are described.

A Rat carotidienne Balloon Modèle de lésion pour tester Therapeutics Rénovation Anti-vasculaires

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is ...

Intraluminal Drug Delivery to the Mouse Arteriovenous Fistula Endothelium

Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The simple murine AVF model was combined with intraluminal administration of drug solution to the venous endothelium at the same time as fistula creation. Technical aspects of this model are discussed. Under general anesthesia, an abdominal incision is made and the aorta and inferior vena cava (IVC) are exposed. The infra-renal aorta and IVC are dissected for clamping. After proximal and distal clamping, the puncture site is exposed and a 25 G needle is used to puncture both walls of the aorta and into the IVC. Immediately after the puncture, a reporter gene-expressing viral vector was infused in the IVC via the same needle, followed by 15 min of incubation. The intraluminal administration method enabled more robust viral gene delivery to the venous endothelium compared to administration by the external route. This novel method of delivery will facilitate studies that explore the role of the endothelium in AVF maturation and enable intraluminal drug delivery at the time of surgical operation.

After puncturing the aorta through the inferior vena cava (IVC) to create an aorto-caval fistula in the mouse, solution containing a drug is infused into the IVC via the same needle, followed by incubation. This method enables more robust drug delivery to the venous endothelium compared to the external route.

Intraluminale Drug Delivery à la souris fistule artério-endothélium

Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The ...

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

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

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

Le modèle du lapin d’athérosclérose accélérée : un point de vue méthodologique de la blessure de ballon artère iliaque

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

Phase Contrast Magnetic Resonance Imaging in the Rat Common Carotid Artery

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous studies have shown that abnormal blood flow may be associated with systemic vascular risk. Thus, PC-MRI can facilitate the translation of data obtained from animal models of cardiovascular diseases to pertinent clinical investigations. In this report, we describe the procedure for measuring blood flow in the common carotid artery (CCA) of rats using cine-gated PC-MRI and discuss relevant analysis methods. This procedure can be performed in a live, anesthetized animal and does not require euthanasia after the procedure. The proposed scanning parameters yield repeatable measurements for blood flow, indicating excellent reproducibility of the results. The PC-MRI procedure described in this article can be used for pharmacological testing, pathophysiological assessment, and cerebral hemodynamics evaluation.

The overall goal of this procedure is to measure the blood flow in the rat common carotid artery by using noninvasive phase contrast magnetic resonance imaging.

Phase contraste d’imagerie par résonance magnétique dans l’artère carotide commune de Rat

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous ...

Ferric Chloride-induced Canine Carotid Artery Thrombosis: A Large Animal Model of Vascular Injury

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, we have translated a vascular injury model from a small animal into a large animal (canine), with slight modifications that can be used for pre-clinical screening of prophylactic and thrombolytic agents. In addition to the surgical methods, the modified protocol describes the step-by-step methods to assess carotid artery canalization by angiography, detailed instructions to process both the brain and carotid artery for histological analysis to verify carotid canalization and cerebral hemorrhage, and specific parameters to complete an assessment of downstream thromboembolic events by utilizing magnetic resonance imaging (MRI). In addition, specific procedural changes from the previously well-established small animal model necessary to translate into a large animal (canine) vascular injury are discussed.

Here, we present the modifications necessary to a well characterized and commonly used small animal ferric chloride-induced (FeCl3) carotid artery injury model for use in a large animal vascular injury model. The resulting model can be utilized for pre-clinical trial assessment of both prophylactic and thrombolytic pharmacological and mechanical interventions.

Thrombose de l’artère carotide Canine induite par le chlorure ferrique : Un grand modèle Animal de lésion vasculaire

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, ...

Middle Cerebral Artery Occlusion Allowing Reperfusion via Common Carotid Artery Repair in Mice

The ischemic stroke is a major cause of adult long-term disability and death worldwide. The current treatments available are limited, with only tissue plasminogen activator (tPA) as an approved drug treatment to target ischemic strokes. Current research in the field of ischemic stroke focuses on better understanding the pathophysiology of stroke, to develop and investigate novel pharmaceutical targets. Reliable experimental stroke models are crucial for the progression of potential treatments. The middle cerebral artery occlusion (MCAO) model is clinically relevant and the most frequently used surgical model of ischemic stroke in rodents. However, the outcomes of this model, such as lesion volume, are associated with high levels of variability, particularly in mice. The alternative MCAO model described here allows the reperfusion of the common carotid artery (CCA) and the increased perfusion of the middle cerebral artery (MCA) territory, using a tissue pad with fibrinogen-based sealant to repair the vessel, and the improved welfare of the mice by avoiding external carotid artery (ECA) ligation. This reduces the reliance on the Circle of Willis, which is known to be highly anatomically variable in mice. Representative data show that using this alternative surgical approach decreases the variability in lesion volumes between the traditional MCAO approach and the alternative approach described here.

Intraluminal filament occlusion of the middle cerebral artery is the most frequently used in vivo model of experimental stroke in rodents. An alternative surgical approach to allow common carotid artery repair is performed here, which allows the reperfusion of the common carotid artery and a full reperfusion to the middle cerebral artery territory.

Occlusion de l’artère cérébrale moyenne permettant une Reperfusion par l’intermédiaire de réparation de l’artère carotide commune chez les souris

The ischemic stroke is a major cause of adult long-term disability and death worldwide. The current treatments available are limited, with only tissue ...