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

注：ラットバルーン損傷モデルおよび組換えのsRAGEと超音波超音波検査の研究の注入を含む、関連する手順の使用は、国立老化研究所の動物実験委員会（ACUC）、NIHによって承認されています。 1.手術前の準備<ol><li>インストゥルメント、外科プラットフォーム、および個人装備。 <ol><li>この手順で使用するすべての手術器具および試薬のための材料および機器の表を参照してください。外科手術の前に、すべての手術器具をオートクレーブ。 注：同じ日に実行される複数の手術の場合、手術の間に器具を滅菌するために予備加熱したガラスビーズ滅菌器を使用しています。 </li><li> 70％アルコールでオペレーティングプラットフォームの表面を殺菌します。手術用ガウン、ヘアカバー、外科手術用マスク、保護眼鏡、と手袋を着用してください。追加の私たちのための外科的なプ​​ラットフォームの近くに滅菌手袋のボックスを残します電子。 </li></ol></li><li>バルーンカテーテルの準備。 <ol><li>滅菌水で1ミリリットル注射器を記入し、滅菌水で満たされた2方コックに注射器を取り付けます。静かにバルーンカテーテルのルアーロック部を記入し、カテーテルの開口部から気泡を除去するためにストップコックを通して水をプッシュ。 </li><li>バルーンを保証するテストバルーン膨張は、水0.02mlのことで膨張させることができます。乾燥や汚染を避けるために手術前に滅菌水の容器にバルーンの先端に保管してください。 </li></ol></li><li>麻酔と動物の準備。 <ol><li> Wistar系雄性ラット（400〜450グラム）を計量し、IDを確認するために、耳のタグを確認してください。このようなつま先や尾をつまんとしてペダル引っ込め反射をチェックすることによって、鎮静の深さを確認し、誘導チャンバー内にラットを置き、その後、気化器をオンにして1.5〜2.0 Lに3.5から4.0パーセントにイソフルランレベルと酸素レベルを調整動物の。 </li><li>麻酔に達した後（ <em&gt;動物）はペダル引っ込め反射を欠いている。すなわち、外科的なプラットフォームに動物を転送し、麻酔気化器に接続するノーズコーンとラットをフック。 L.は、定期的にラットが完全にリラックスして不動であることを確実にするために、動物のつま先や尾をつまんで鎮静の深さを確認して0.6から1.0に1.5から2.0と酸素にイソフルラン濃度を調整します。 </li><li>麻酔の外科的なレベルに到達した後、単に動物のバリカンと胸骨の上までchinから腹側ネック領域を剃るし、ポビドンヨードおよび70％エタノールで3回の1:10希釈液を交互に剃毛した皮膚を綿棒。 </li><li>乾燥からそれらを防ぐために、綿棒で動物の開いた目に点眼液を置きます。動作中の乾燥を避けるために、水を飲んで動物の舌と口を湿ら。 </li><li>無菌手術用シートでラットを覆い、ネック領域を露出させるためにシートをカット。仰臥位のOに動物を置きます外科医に向かって頭を手術用プラットフォーム上のパッド加熱ナ。テープを使用して、手術用プラットフォームに動物の手足を修正しました。 </li></ol></li></ol> 2.外科的処置<ol><li>左頸動脈の解剖と単離<ol><li>ちょうど胸郭の上に尾部に向かう方向に胸骨の先頭にすべての方法を顎の下のストレート切開を作るためにメスを使用してください。ぶっきらぼうに筋層を露出させるために皮膚の下唾液腺組織を分析する7S鉗子を使用してください。頸動脈管構造とネック領域における迷走神経へのアクセスを獲得するために別の筋肉組織。 </li><li>ぶっきらぼうに頸動脈を周囲の組織を解剖し、慎重に任意の損傷を避けるために迷走神経と血管筋膜を分離します。継続的にダウンして胸骨の内部および外部の支店および総頸動脈を露出させるために頸動脈分岐部まで解剖します。 </li></ol></li><li> Arteriotの調製大丸有<ol><li>後退や止血のために、左総頸動脈に最も近位のサイトで合字を置き、分岐点に位置即時遠位にある別のリガチャー。 </li><li>頭に向かって動脈を後退させるためにできる限りの分岐部から外頸動脈で4.0絹縫合糸を配置します。永久昇順咽頭、後頭動脈漏れを回避するための優れた甲状腺を含む外頸動脈に沿って4.0絹縫合糸を用いて、小動脈を結紮。 </li><li>重大な逆行性の血液の損失を回避するために、内頸動脈の周りに4.0絹縫合糸を配置します。通常、内部分岐の利用可能な長さは最小です。内頚動脈を可視化するために、静かに右に、上にある頸動脈を後退させることにより可能な限り内頸動脈を露出させます。 </li></ol></li><li>バルーンカテーテルの導入<ol><li>総頸動Aの近位縫合糸を撤回rteryとは、一時的に血流を止めるために、血管に動脈クランプを配置します。できるだけ縫合糸のよう遠位位置で外頸動脈に（1/3動脈の円周の1/4）に小切開を加えます。 </li><li>優しく切開部に未膨張バルーンカテーテルを挿入し、総頸動脈に動脈クランプに近い内腔にカテーテルを進めます。クランプを外し、さらに切開から約35〜40ミリメートル、大動脈弓にバルーンカテーテルを進めます。 </li></ol></li><li>バルーン傷害<ol><li>手動で添付シリンジを介して0.02ミリリットルの容量にカテーテルを膨張し、その後、注射器とカテーテルとの間のコックをロックします。ゆっくりと回転してカテーテルを引き抜きます。カテーテルはarteriotomic切開部に近接している場合には、バルーンを収縮させます。元の場所にカテーテルを進めます。 </li><li>合計3回2.4.1を繰り返します。慎重に動脈内腔からカテーテルを除去します。 </li></ol></li><li>手術創をクローズアップ<ol><li>縫合糸で動脈切開を閉じます。血流を回復するために内頸動脈をリリース。動脈出血やリークを確認してください。出血が発生した場合は、出血を止めるために、ビット圧力でガーゼを適用します。 </li><li>手続きのために使用される縫合糸およびクランプの残りの部分を削除します。 6.0縫合糸で腺組織を閉じます。皮膚の縫合糸または創傷クリップで皮膚を閉じます。イソフルランの電源を切り、数分間、純酸素で動物を残します。 </li></ol></li></ol> 3.治療薬の投与は、鎮痛薬、手術後のケア、および安楽死<ol><li>治療薬や鎮痛剤の投与。 <ol><li>手術後、筋肉内にブプレノルフィン（0.03ミリグラム/キログラム）を注入します。手術中に血液の損失を補償するために、5ミリリットル予め温めた滅菌生理食塩水を皮下に注入します。腹膜へのsRAGE（0.5 ngの/ g）を（治療薬）を注入します。 </li><li> OPHで再び目を湿らthalmic軟膏。熱パッドの上にラットを置き、胸骨横臥位を維持するために完全な意識を取り戻すまで、動物を監視します。 </li><li>きれいな寝具を使用してケージにラットを戻し、バックビバリウムにケージを持参。出席獣医師や世話人を警告するためにケージに特殊な観測カードを置きます。 </li></ol></li><li>術後のクリーンアップ<ol><li>ゴミや特殊な廃棄容器へのいずれかの針らパッド、綿棒、を含む使用済みの外科材料を入れてください。手術プラットフォームを消毒し、手術器具を清掃してください。 </li></ol></li><li>術後のケア<ol><li> 48時間後に手術期間中にブプレノルフィン（0.03ミリグラム/キログラム）一日二回（BID）を管理します。このような不動、養うことができないこと、hutched姿勢、フリル毛皮、としかめっ面のような苦痛の一般的な徴候のための48時間術後期間中に密接に動物を監視します。創傷赤みのための条件、腫れ、裂開、および感染症を監視します。 注意：追加の治療は、獣医師の勧告に出席に応じて処方されることがあります。 </li><li>獣医師の勧告に出席に応じて縫合または創傷クリップを削除します。 </li></ol></li><li>安楽死<ol><li>手術の2週間後に、22を分析し 、死後ヒスト形態学のための頸動脈を分離するために、ラットを安楽死させます。呼吸の完全な停止するまで、少なくとも2分間、空気を飽和5から20までパーセントイソフルランを含むチャンバーにラットを置きます。前の器官および組織の切開に死を確認します。 </li></ol></li></ol>

<ol>
	<li>Chaabane, C., Otsuka, F., Virmani, R., Bochaton-Piallat, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Biological+responses+in+stented+arteries.">Biological responses in stented arteries.</a> Cardiovasc Res. 99, 353-363 (2013).</li><li>Goel, S. A., Guo, L. W., Liu, B., Kent, K. C. <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+post-intervention+arterial+remodelling.">Mechanisms of post-intervention arterial remodelling.</a> Cardiovasc Res. 96, 363-371 (2012).</li><li>Khan, R., Agrotis, A., Bobik, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Understanding+the+role+of+transforming+growth+factor-beta1+in+intimal+thickening+after+vascular+injury.">Understanding the role of transforming growth factor-beta1 in intimal thickening after vascular injury.</a> Cardiovasc Res. 74, 223-234 (2007).</li><li>Schillinger, M., Minar, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Restenosis+after+percutaneous+angioplasty:+the+role+of+vascular+inflammation.">Restenosis after percutaneous angioplasty: the role of vascular inflammation.</a> Vasc Health Risk Manag. 1, 73-78 (2005).</li><li>Katz, G., Harchandani, B., Shah, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drug-eluting+stents:+the+past,+present,+and+future.">Drug-eluting stents: the past, present, and future.</a> Curr Atheroscler Rep. 17, 485 (2015).</li><li>Jain, M., Singh, A., Singh, V., Barthwal, M. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Involvement+of+Interleukin-1+Receptor-Associated+Kinase-1+in+Vascular+Smooth+Muscle+Cell+Proliferation+and+Neointimal+Formation+After+Rat+Carotid+Injury.">Involvement of Interleukin-1 Receptor-Associated Kinase-1 in Vascular Smooth Muscle Cell Proliferation and Neointimal Formation After Rat Carotid Injury.</a> Arterioscler Thromb Vasc Biol. , (2015).</li><li>Lee, K. P., 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=Carvacrol+inhibits+atherosclerotic+neointima+formation+by+downregulating+reactive+oxygen+species+production+in+vascular+smooth+muscle+cells.">Carvacrol inhibits atherosclerotic neointima formation by downregulating reactive oxygen species production in vascular smooth muscle cells.</a> Atherosclerosis. 240, 367-373 (2015).</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 (12), 1362-1365 (2000).</li><li>Noda, 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=New+endoplasmic+reticulum+stress+regulator,+gipie,+regulates+the+survival+of+vascular+smooth+muscle+cells+and+the+neointima+formation+after+vascular+injury.">New endoplasmic reticulum stress regulator, gipie, regulates the survival of vascular smooth muscle cells and the neointima formation after vascular injury.</a> Arterioscler Thromb Vasc Biol. 35 (5), 1246-1253 (2015).</li><li>Deuse, 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=Dichloroacetate+prevents+restenosis+in+preclinical+animal+models+of+vessel+injury.">Dichloroacetate prevents restenosis in preclinical animal models of vessel injury.</a> Nature. 509 (7502), 641-644 (2014).</li><li>Guo, 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=p55gamma+functional+mimetic+peptide+N24+blocks+vascular+proliferative+disorders.">p55gamma functional mimetic peptide N24 blocks vascular proliferative disorders.</a> J Mol Med (Berl). , (2015).</li><li>Oh, C. 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=Dimethylfumarate+attenuates+restenosis+after+acute+vascular+injury+by+cell-specific+and+Nrf2-dependent+mechanisms.">Dimethylfumarate attenuates restenosis after acute vascular injury by cell-specific and Nrf2-dependent mechanisms.</a> Redox Biol. 2, 855-864 (2014).</li><li>Tae, H. 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=The+N-glycoform+of+sRAGE+is+the+key+determinant+for+its+therapeutic+efficacy+to+attenuate+injury-elicited+arterial+inflammation+and+neointimal+growth.">The N-glycoform of sRAGE is the key determinant for its therapeutic efficacy to attenuate injury-elicited arterial inflammation and neointimal growth.</a> J Mol Med (Berl. 91 (12), 1369-1381 (2013).</li><li>Zhou, Z., 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=Receptor+for+AGE+(RAGE)+mediates+neointimal+formation+in+response+to+arterial+injury.">Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury.</a> Circulation. 107 (17), 2238-2243 (2003).</li><li>Lindner, V., Fingerle, J., Reidy, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+model+of+arterial+injury.">Mouse model of arterial injury.</a> Circ Res. 73 (5), 792-796 (1993).</li><li>Le, V., Johnson, C. G., Lee, J. D., Baker, A. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Murine+model+of+femoral+artery+wire+injury+with+implantation+of+a+perivascular+drug+delivery+patch.">Murine model of femoral artery wire injury with implantation of a perivascular drug delivery patch.</a> J Vis Exp. (96), e52403 (2015).</li><li>Iannaccone, P. M., Jacob, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rats!+.">Rats! .</a> Dis Model Mech. 2 (5-6), 206-210 (2009).</li><li>Fu, Y., Sander, J. D., Reyon, D., Cascio, V. M., Joung, J. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improving+CRISPR-Cas+nuclease+specificity+using+truncated+guide+RNAs.">Improving CRISPR-Cas nuclease specificity using truncated guide RNAs.</a> Nat Biotechnol. 32 (3), 279-284 (2014).</li><li>Sander, J. D., Joung, J. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CRISPR-Cas+systems+for+editing,+regulating+and+targeting+genomes.">CRISPR-Cas systems for editing, regulating and targeting genomes.</a> Nat Biotechnol. 32 (4), 347-355 (2014).</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 Mol Med. 139, 1-30 (2007).</li><li>Zhang, W., Trebak, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vascular+balloon+injury+and+intraluminal+administration+in+rat+carotid+artery.">Vascular balloon injury and intraluminal administration in rat carotid artery.</a> J Vis Exp. (94), (2014).</li><li>Tae, H. 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=Vessel+ultrasound+sonographic+assessment+of+soluble+receptor+for+advanced+glycation+end+products+efficacy+in+a+rat+balloon+injury+model.">Vessel ultrasound sonographic assessment of soluble receptor for advanced glycation end products efficacy in a rat balloon injury model.</a> Curr Ther Res Clin Exp. 76, 110-115 (2014).</li><li>Tae, H. 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=Chronic+treatment+with+a+broad-spectrum+metalloproteinase+inhibitor,+doxycycline,+prevents+the+development+of+spontaneous+aortic+lesions+in+a+mouse+model+of+vascular+Ehlers-Danlos+syndrome.">Chronic treatment with a broad-spectrum metalloproteinase inhibitor, doxycycline, prevents the development of spontaneous aortic lesions in a mouse model of vascular Ehlers-Danlos syndrome.</a> J Pharmacol Exp Ther. 343 (1), 246-251 (2012).</li><li>Sakaguchi, 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=Central+role+of+RAGE-dependent+neointimal+expansion+in+arterial+restenosis.">Central role of RAGE-dependent neointimal expansion in arterial restenosis.</a> J Clin Invest. 111 (7), 959-972 (2003).</li></ol>

著者は、彼らが競合する金融利害関係を持たないことを宣言します。

頚動脈の動脈内腔で壁画内皮を除去損傷を生成するためにバルーンを膨張させるために使用される二つの方法がありました。一つは、液体20を取り付けた注射器を充填することであり、他方は空気圧21を使用することです。我々は、正確な液量（0.02 ml）を各手順に使用されるので、液体が充填された注射器を使用することを好みます。これは、処置を受けて各動物における損?...

血管形成術は、アテローム性動脈硬化症のような病理学的状態から得られる狭めたり閉塞した動脈を広げるために使用される血管内処置です。血管形成術の一つの一般的な合併症は、外科的傷害とその後の炎症誘発性血管リモデリングにより発生した後の運用の新生内膜過形成、または再狭窄、です。これらの条件は、血管平滑筋細胞の増殖、および複数の病態生理学的な結果1-3につながります。新生内膜過形成の容器を再厚く、かつ1年以内に60％まで血管形成後の患者の中で起こります。したがって、再狭窄は、広く使用されている血管形成術手順4の主要な後退です。薬剤溶出ステントの植え込みは、再狭窄を防止するのに役立つかもしれないが、唯一の選択された候補は、この費用のかかる手順5を受けることができます。 動物および臨床研究の両方が慢性炎症がvascuによって生成されたことを確立しましたLAR傷害および/ ​​または手術創は、血管形成後の新生内膜増殖2,4のための主要な刺激として機能します。ラット頸動脈バルーン損傷モデルは、臨床的状況を模倣し、従って、血管リモデリングおよび血管細胞増殖6-9に関与する細胞因子を同定するための貴重なモデルシステムとして機能します。このモデル系は、また、前臨床翻訳研究10-14における新生内膜増殖を抑制する薬物および治療 ​​薬のために非常に有用で評価するためのツール及び/又はスクリーンです。 マウス頸動脈ワイヤ傷害モデル15およびマウス大腿動脈ワイヤ傷害モデル16に比べて、ラット頸動脈バルーン傷害モデルが与え損傷の再現性を容易にする外科的処置を容易にするためにサイズが十分に大きいという利点を有します。これはADDITための一次細胞の多く（ 例えば 、血管平滑筋細胞、内皮細胞）を提供することができますional インビトロ血管リモデリングを支配する分子機構を描くための研究。重要なことには、マウスに比べて、ラットにも生理学的および毒性試験17のためのより良いモデルであることが知られています。ラットモデルの欠点または制限が変更された遺伝的および遺伝子ノックアウトモデルの欠如であるが、この欠点は、ラットゲノム配列の可用性と、このようなレンダリングCRISPR-CAS技術などの強力なゲノム編集ツールの最近の開発によって克服することができます異なるモデル系18,19におけるゲノム配列の広大な範囲の可能な操作。 ラットバルーン傷害モデルでは、複数のラボや様々な包括的なプロトコルで使用されてきたが20,21を公開されている、このプロトコルは、手術前の準備でより詳細な情報を提供することを目的とし、この外科的な練習をセットアップするには、この手順に新しい研究者を案内することができます。また、トンの術後のケアを重視します生きた動物13,22だけでなく、動脈リモデリングに対する治療効果の死後の病理学的および組織形態学的分析だけでなく、超音波超音波検査の研究ができます彼の動物。

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			<td height="21" style="height:21px;width:287px;">2 F Fogarty balloon embolectomy catheter&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</td>
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			<td height="21" style="height:21px;width:287px;">Compact hot bead sterilizer</td>
			<td style="width:163px;">Fine Science Tools</td>
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			<td height="21" style="height:21px;width:287px;">Self-regulating heating pad</td>
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			<td height="21" style="height:21px;width:287px;">Isoflurane (forane), liquid form</td>
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			<td style="width:163px;">Reckitt Benckiser Healthcare (UK) Ltd.&#160;</td>
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			<td style="width:163px;">Fisher</td>
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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.

二週間バルー​​ン損傷後、ラットを安楽死させられ、頸動脈はヒスト形態素解析のために単離されます。両方とも、左頸動脈および非作動右動脈は、断面に処理され、パラフィン包埋されている操作しました。パラフィン次いで、サンプルをさらに薄い切片であり、そしてヘマトキシリン​​ - エオシン（H＆E）で染色しました。ヒスト形態学的分析は、デジタル?...

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

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

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

ラット頸動脈バルーン損傷モデルは、抗血管リモデリングの治療薬をテストします

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 ...

a-rat-carotid-balloon-injury-model-to-test-anti-vascular-remodeling

Research

JoVE Journal

Medicine

8.6K ビュー.  National Institute on Aging. The rat carotid balloon injury model described below allows researchers to evaluate drugs or therapeutics that negate injury-induced arterial hyperplasia. Detailed pre-surgical preparation, surgical procedure, and post-surgical cares of the animal are described. 

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

Intranasal Administration of CNS Therapeutics to Awake Mice

Intranasal administration is a method of delivering therapeutic agents to the central nervous system (CNS). It is non-invasive and allows large molecules that do not cross the blood-brain barrier access to the CNS. Drugs are directly targeted to the CNS with intranasal delivery, reducing systemic exposure and thus unwanted systemic side effects1. Delivery from the nose to the CNS occurs within minutes along both the olfactory and trigeminal neural pathways via an extracellular route and does not require drug to bind to any receptor or axonal transport2. Intranasal delivery is a widely publicized method and is currently being used in human clinical trials3.
Intranasal delivery of drugs in animal models allows for initial evaluation of pharmacokinetic distribution and efficacy. With mice, it is possible to administer drugs to awake (non-anesthetized) animals on a regular basis using a specialized intranasal grip. Awake delivery is beneficial because it allows for long-term chronic dosing without anesthesia, it takes less time than with anesthesia, and can be learned and done by many people so that teams of technicians can dose large numbers of mice in short periods. Efficacy of therapeutics administered intranasally in this way to mice has been demonstrated in a number of studies including insulin in diabetic mouse models 4-6 and deferoxamine in Alzheimer's mouse models. 7,8
The intranasal grip for mice can be learned, but is not easy and requires practice, skill, and a precise grip to effectively deliver drug to the brain and avoid drainage to the lung and stomach. Mice are restrained by hand using a modified scruff in the non-dominant hand with the neck held parallel to the floor, while drug is delivered with a pipettor using the dominant hand. It usually takes 3-4 weeks of acclimating to handling before mice can be held with this grip without a stress response. We have prepared this JoVE video to make this intranasal delivery technique more accessible.

A method to intranasally administer drugs to awake mice for the purpose of targeting the brain is described. This method allows for repeat dosing over long periods using intranasal administration of drug without anesthesia, and nose-to-brain delivery with minimal systemic exposure.

アウェイクマウスに対する中枢神経系治療薬の経鼻投与

Intranasal administration is a method of delivering  therapeutic agents to the central nervous system (CNS). It is  non-invasive and allows large ...

医学

Rat Model of Blood-brain Barrier Disruption to Allow Targeted Neurovascular Therapeutics

Endothelial cells with tight junctions along with the basement membrane and astrocyte end feet surround cerebral blood vessels to form the blood-brain barrier1. The barrier selectively excludes molecules from crossing between the blood and the brain based upon their size and charge. This function can impede the delivery of therapeutics for neurological disorders. A number of chemotherapeutic drugs, for example, will not effectively cross the blood-brain barrier to reach tumor cells2. Thus, improving the delivery of drugs across the blood-brain barrier is an area of interest.
The most prevalent methods for enhancing the delivery of drugs to the brain are direct cerebral infusion and blood-brain barrier disruption3. Direct intracerebral infusion guarantees that therapies reach the brain; however, this method has a limited ability to disperse the drug4. Blood-brain barrier disruption (BBBD) allows drugs to flow directly from the circulatory system into the brain and thus more effectively reach dispersed tumor cells. Three methods of barrier disruption include osmotic barrier disruption, pharmacological barrier disruption, and focused ultrasound with microbubbles. Osmotic disruption, pioneered by Neuwelt, uses a hypertonic solution of 25% mannitol that dehydrates the cells of the blood-brain barrier causing them to shrink and disrupt their tight junctions. Barrier disruption can also be accomplished pharmacologically with vasoactive compounds such as histamine5 and bradykinin6. This method, however, is selective primarily for the brain-tumor barrier7. Additionally, RMP-7, an analog of the peptide bradykinin, was found to be inferior when compared head-to-head with osmotic BBBD with 25% mannitol8. Another method, focused ultrasound (FUS) in conjunction with microbubble ultrasound contrast agents, has also been shown to reversibly open the blood-brain barrier9. In comparison to FUS, though, 25% mannitol has a longer history of safety in human patients that makes it a proven tool for translational research10-12.
In order to accomplish BBBD, mannitol must be delivered at a high rate directly into the brain's arterial circulation. In humans, an endovascular catheter is guided to the brain where rapid, direct flow can be accomplished. This protocol models human BBBD as closely as possible. Following a cut-down to the bifurcation of the common carotid artery, a catheter is inserted retrograde into the ECA and used to deliver mannitol directly into the internal carotid artery (ICA) circulation. Propofol and N2O anesthesia are used for their ability to maximize the effectiveness of barrier disruption13. If executed properly, this procedure has the ability to safely, effectively, and reversibly open the blood-brain barrier and improve the delivery of drugs that do not ordinarily reach the brain 8,13,14.

Blood-brain barrier disruption aids the delivery of certain drugs to the brain. Mannitol delivered intra-arterially shrinks cells surrounding blood vessels in order to physically disrupt the barrier.

血液脳関門の破壊のラットモデルは、対象となる神経血管治療を許可する

Endothelial cells with tight junctions along with the basement membrane and astrocyte end feet surround cerebral blood vessels to form the blood-brain ...

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.

マウスにおけるタキサンの薬物動態学的および薬力学的分析のための頸動脈煎茶

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 ...

Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery

The carotid artery balloon injury model in rats has been well established for over two decades. It remains an important method to study the molecular and cellular mechanisms involved in vascular smooth muscle dedifferentiation, neointima formation and vascular remodeling. Male Sprague-Dawley rats are the most frequently employed animals for this model. Female rats are not preferred as female hormones are protective against vascular diseases and thus introduce a variation into this procedure. The left carotid is typically injured with the right carotid serving as a negative control. Left carotid injury is caused by the inflated balloon that denudes the endothelium and distends the vessel wall. Following injury, potential therapeutic strategies such as the use of pharmacological compounds and either gene or shRNA transfer can be evaluated. Typically for gene or shRNA transfer, the injured section of the vessel lumen is locally transduced for 30 min with viral particles encoding either a protein or shRNA for delivery and expression in the injured vessel wall. Neointimal thickening representing proliferative vascular smooth muscle cells usually peaks at 2 weeks after injury. Vessels are mostly harvested at this time point for cellular and molecular analysis of cell signaling pathways as well as gene and protein expression. Vessels can also be harvested at earlier time points to determine the onset of expression and/or activation of a specific protein or pathway, depending on the experimental aims intended. Vessels can be characterized and evaluated using histological staining, immunohistochemistry, protein/mRNA assays, and activity assays. The intact right carotid artery from the same animal is an ideal internal control. Injury-induced changes in molecular and cellular parameters can be evaluated by comparing the injured artery to the internal right control artery. Likewise, therapeutic modalities can be evaluated by comparing the injured and treated artery to the control injured only artery.

This protocol uses a balloon catheter to cause an intraluminal injury on the rat carotid artery and henceforth elicit neointimal hyperplasia. This is a well-established model for studying the mechanisms of vascular remodeling in response to injury. It is also widely used to determine the validity of potential therapeutic approaches.

ラット頸動脈における血管バルーン傷害と管腔内投与

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 ...

Retroductal Submandibular Gland Instillation and Localized Fractionated Irradiation in a Rat Model of Salivary Hypofunction

Normal tissues that lie within the portals of radiation are inadvertently damaged. Salivary glands are often injured during head and neck radiotherapy. Irreparable cell damage results in a chronic loss of salivary function that impairs basic oral activities, and increases the risk of oral infections and dental caries. Salivary hypofunction and its complications gravely impact a patient's comfort. Current symptomatic management of the condition is ineffective, and newer therapies to assuage the condition are needed. 
Salivary glands are exocrine glands, which expel their secretions into the mouth via excretory ducts. Cannulation of these ducts provides direct access to the glands. Retroductal delivery of a contrast agent to major salivary glands is a routine out-patient procedure for diagnostic imaging. Using a similar procedure, localized treatment of the glands is feasible. However, performing this technique in preclinical studies with small animals poses unique challenges. In this study we describe the technique of retroductal administration in rat submandibular glands, a procedure that was refined in Dr. Bruce Baum's laboratory (NIH)1, and lay out a procedure for local gland irradiation.

Salivary gland hypofunction, a major adverse effect of head and neck radiotherapy diminishes a patient's quality of life. The demonstration of efficacy of new therapies in animal models is a prerequisite before clinical transition. This protocol describes retroductal administration and local irradiation of rat submandibular glands.

唾液機能低下のラットモデルにおけるRetroductal顎下腺点滴とローカライズされた分割照射

Normal tissues that lie within the portals of radiation are inadvertently damaged. Salivary glands are often injured during head and neck radiotherapy. ...

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.

加速動脈硬化家兎モデル: 内腸骨動脈バルーン傷害の方法論的視点

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

Balloon-based Injury to Induce Myointimal Hyperplasia in the Mouse Abdominal Aorta

The use of animal models is essential for a better understanding of MH, one major cause for arterial stenosis.In this article, we demonstrate a murine balloon denudation model, which is comparable with established vessel injury models in large animals. The aorta denudation model with balloon catheters mimics the clinical setting and leads to comparable pathobiological and physiological changes. Briefly, after performing a horizontal incision in the aorta abdominalis, a balloon catheter will be inserted into the vessel, inflated, and introduced retrogradely. Inflation of the balloon will lead to intima injury and overdistension of the vessel. After removing the catheter, the aortic incision will be closed with single stiches. The model shown in this article is reproducible, easy to perform, and can be established quickly and reliably. It is especially suitable for evaluating expensive experimental therapeutic agents, which can be applied in an economical fashion. By using different knockout-mouse strains, the impact of different genes on MH development can be assessed.

This article demonstrates a murine model to study the development of myointimal hyperplasia (MH) after aortic balloon injury.

マウスの腹部大動脈 Myointimal 過形成を誘導するために気球を利用した傷害

The use of animal models is essential for a better understanding of MH, one major cause for arterial stenosis.In this article, we demonstrate a murine ...

A Drosophila In Vivo Injury Model for Studying Neuroregeneration in the Peripheral and Central Nervous System

The regrowth capacity of damaged neurons governs neuroregeneration and functional recovery after nervous system trauma. Over the past few decades, various intrinsic and extrinsic inhibitory factors involved in the restriction of axon regeneration have been identified. However, simply removing these inhibitory cues is insufficient for successful regeneration, indicating the existence of additional regulatory machinery. Drosophila melanogaster, the fruit fly, shares evolutionarily conserved genes and signaling pathways with vertebrates, including humans. Combining the powerful genetic toolbox of flies with two-photon laser axotomy/dendriotomy, we describe here the Drosophila sensory neuron &#8211; dendritic arborization (da) neuron injury model as a platform for systematically screening for novel regeneration regulators. Briefly, this paradigm includes a) the preparation of larvae, b) lesion induction to dendrite(s) or axon(s) using a two-photon laser, c) live confocal imaging post-injury and d) data analysis. Our model enables highly reproducible injury of single labeled neurons, axons, and dendrites of well-defined neuronal subtypes, in both the peripheral and central nervous system.

A Drosophila In Vivo Injury Model for Studying Neuroregeneration in the Peripheral and Central Nervous System

Here, we present a protocol using the Drosophila sensory neuron - dendritic arborization (da) neuron injury model, which combines in vivo live imaging, two-photon laser axotomy/dendriotomy, and the powerful fly genetic toolbox, as a platform for screening potential promoters and inhibitors of neuroregeneration.

再生に関する末梢および中枢神経系を研究するため生体内でショウジョウバエ損傷モデル

The regrowth capacity of damaged neurons governs neuroregeneration and functional recovery after nervous system trauma. Over the past few decades, various ...

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.

塩化第二鉄によるイヌ総頚動脈血栓症: 血管損傷の大動物モデル

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

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

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

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

過期治療アプリケーションを用いてラット頸動脈圧制御区分バルーン損傷

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