現在の研究はSolorz - ザック研究財団によって資金を供給される。

すべての外科的処置は、倫理審査を受け、バイエルンの政府によって承認された（参照番号：55.2-1-54-2532.3-13-13と-2532-136-11）。動物は、約25gの体重の雄C57BL / 6マウスである。 1。動物の準備<ol><li>チャンバー内にマウスを置くことによって麻酔を誘導する。動物が意識を失うまで、5％イソフルランでチャンバーをフラッシュします。 </li><li>腹腔内に予混合麻酔薬を注入：フェンタニル（0.​​05 mg / kg）を、ミダゾラム（5 mg / kg）をし、メデトミジン（0.5 mg / kg）を。手順の間に前と定期的に反射神経をチェックしてください。麻酔を維持するために時間ごとに初期量の3分の1を再注入。 </li><li> 20 Gの静脈カテーテル11から作られたチューブを挿管orotracheally。挿管のために、曲がったピンセットで舌を引っ込める手術用顕微鏡下に声帯を視覚化し、気管にチューブを挿入し、傾斜プラットフォーム（30°）で動物を修正吸気時。 </li><li>腹臥位でマウスを置き、木綿のピースまたはmicrocapnographでチューブの正しい配置を確認してください。 </li><li>呼吸器への挿管チューブを接続します。 180〜220回/分であり、200〜250μLの拍出量の周波数で25％の酸素を補給し室内空気とマウスを換気する。 </li><li> microcapnographに挿管チューブを接続します。換気回数を調整することにより、30 mmHgので呼気終末PCO 2を維持する。 </li><li>直腸温度プローブを挿入し、37℃の中核体温を維持するために、加熱パッド上に動物を置く。 </li><li>右後肢に環状pulsoximeterセンサーを適用します。 </li><li>はさみで頭蓋骨の上の皮膚を開きます。切開は約0.5cm、長と耳と目の間でなければなりません。 </li><li>頭骨のメスで、左側頭筋を解剖。 </li><li>レーザードップラー流量計（LDF）プローブにのり左頭骨。接着剤が硬化するまで固定位置にプローブを保持する。 </li><li>左側頭骨に歯科用ドリルで約1.5ミリメートル径の穴を開けます。熱損傷を防止するために、生理食塩水で骨を冷却する。 </li><li>頭蓋腔へのICPプローブを挿入します。脳組織の損傷や出血を防ぐために、背側に可能な限り進めて。 </li><li>プローブが正しい位置にあれば、修正し、セメントでそれを封印。 5分間のセメント乾燥させる。 </li><li>仰臥位に慎重に、マウスの電源を入れます。 </li><li>連続血圧監視のために、左大腿動脈カテーテルを挿入。 </li><li>血圧監視装置に大腿カテーテルを接続します。 </li></ol> 2。 SAH誘導<ol><li>あご（2 CM）への胸骨からハサミで皮膚を開きます。ぶっきらぼうに結合組織を解剖し、脇に唾液腺を押してください。 </li><li>左総頸動脈（CCA）を露出し、それを動員する。守るCCAと同じ結合組織鞘で実行される迷走神経、。頭蓋移動して、同じテクニックを使用してICAとECAを公開し、動員する。 </li><li>限り頭側できるだけECAを結紮。 </li><li> ECAの周りのフィラメントのための2以上のライゲーションを予定する。 </li><li>マイクロクリップで一時的にCCAとICAを塞ぐ。マイクロクリップアプリケーター付きマイクロクリップを配置します。クリップはそっとそれらを引き戻すことで正しく適用されていることを確認します。 </li><li>血管はさみでECAにフィラメントを挿入するための穴をカット。 </li><li> ECAに12ミリメートルの長さとプロレン5-0フィラメントを挿入します。 </li><li> 1事前に決められたライゲーションで挿入部位を閉じます。 </li><li> CCAとICAからマイクロクリップアプリケーターをマイクロクリップを削除します。 </li><li> ICPは上昇するまで、ICAに鉗子でフィラメントを進める。 ICPの急激な上昇は、出血の誘導を示している。 </li><li>すぐにフィラメントを撤回し、PRの両方を閉じることでECAを結紮連続earrangedライゲーション。これは挿入部位からの出血防止します。 </li><li>皮膚創傷を縫合。 </li><li>さらに20分間、動物の生理的パラメータを監視する。 </li><li> ICPおよびLDFプローブを除去し、皮膚創傷を縫合。 </li></ol> 3。実験終了<ol><li> PBS内の20mlの4％PFA（4°C）、続いて食塩水（室温）20mlを経た動物を灌流。 </li><li>頭蓋骨から脳を解剖。正中線に軌道空洞間頭蓋骨を切った。そして、脳から骨をはがします。 </li><li>クモ膜下腔の血分布を評価。 </li></ol> 4。サバイバル手術の場合の考慮事項（ビデオで示されていない） <ol><li>直接麻酔導入後の術後鎮痛のためにカルプロフェン（4 mg / kgを皮下投与）を注入。術後観察期間中カルプロフェン（4 mg / kgを皮下投与）24時間毎に注入される。 </li&gt; <li>代わりに侵襲的​​な血圧測定の非観血血圧モニタリングシステムを利用する。 </li><li>皮下に薬を拮抗麻酔注入の終了のため：ナロキソン（1.2 mg / kg）を、フルマゼニル（0.​​5 mg / kg）をし、アチパメゾール（2.5 mg / kg）を。 </li><li>動物を抜管。 </li><li>反射の回復後に予熱したチャンバー内に動物を入れる。 24時間、約32℃で動物を保​​管してください。 </li><li>動物は、手術後の最初の数時間の間に自発呼吸とその全身状態を定期的にチェックされます。脳幹が影響を受ける場合の動物が問題を呼吸しているし、安楽死させなければならない。 </li><li>動物は、その一般的な状態や体重のためだけでなく、神経学的および感覚欠損15を毎日チェックされます。 </li></ol>

<ol>
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Methods. 123, 89-97 (2003).</li><li>Altay, 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=A+novel+method+for+subarachnoid+hemorrhage+to+induce+vasospasm+in+mice.">A novel method for subarachnoid hemorrhage to induce vasospasm in mice.</a> J. Neurosci. Methods. 183, 136-140 (2009).</li><li>Feiler, S., Friedrich, B., Scholler, K., Thal, S. C., Plesnila, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standardized+induction+of+subarachnoid+hemorrhage+in+mice+by+intracranial+pressure+monitoring.">Standardized induction of subarachnoid hemorrhage in mice by intracranial pressure monitoring.</a> J. Neurosci. Methods. 190, 164-170 (2010).</li><li>Bederson, J. B., Germano, I. 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J., Jakubowski, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Sheffield+model+of+subarachnoid+hemorrhage+in+rats.">The Sheffield model of subarachnoid hemorrhage in rats.</a> Stroke. 26, 1279-1283 (1995).</li><li>Kamii, 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=Amelioration+of+vasospasm+after+subarachnoid+hemorrhage+in+transgenic+mice+overexpressing+CuZn-superoxide+dismutase.">Amelioration of vasospasm after subarachnoid hemorrhage in transgenic mice overexpressing CuZn-superoxide dismutase.</a> Stroke. 30, 867-871 (1999).</li><li>Parra, 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=Mouse+model+of+subarachnoid+hemorrhage+associated+cerebral+vasospasm:+methodological+analysis.">Mouse model of subarachnoid hemorrhage associated cerebral vasospasm: methodological analysis.</a> Neurol. Res. 24, 510-516 (2002).</li><li>Broderick, J. P., Brott, T. G., Duldner, J. E., Tomsick, T., Leach, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Initial+and+recurrent+bleeding+are+the+major+causes+of+death+following+subarachnoid+hemorrhage.">Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage.</a> Stroke. 25, 1342-1347 (1994).</li><li>Thal, S. C., Plesnila, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Non-invasive+intraoperative+monitoring+of+blood+pressure+and+arterial+pCO2+during+surgical+anesthesia+in+mice.">Non-invasive intraoperative monitoring of blood pressure and arterial pCO2 during surgical anesthesia in mice.</a> J. Neurosci. Methods. 159, 261-267 (2007).</li><li>Hockel, K., Trabold, R., Scholler, K., Torok, E., Plesnila, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+anesthesia+on+pathophysiology+and+mortality+following+subarachnoid+hemorrhage+in+rats.">Impact of anesthesia on pathophysiology and mortality following subarachnoid hemorrhage in rats.</a> Exp. Transl. Stroke Med. 4, 5 (2012).</li><li>Wang, Z., Schuler, B., Vogel, O., Arras, M., Vogel, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=What+is+the+optimal+anesthetic+protocol+for+measurements+of+cerebral+autoregulation+in+spontaneously+breathing+mice?.">What is the optimal anesthetic protocol for measurements of cerebral autoregulation in spontaneously breathing mice?.</a> Exp. Brain Res. 207, 249-258 (2010).</li><li>Schwartz, A. Y., Masago, A., Sehba, F. A., Bederson, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+models+of+subarachnoid+hemorrhage+in+the+rat:+a+refinement+of+the+endovascular+filament+model.">Experimental models of subarachnoid hemorrhage in the rat: a refinement of the endovascular filament model.</a> J. Neurosci. Methods. 96, 161-167 (2000).</li><li>Feiler, S., Plesnila, N., Thal, S. C., Zausinger, S., Scholler, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contribution+of+matrix+metalloproteinase-9+to+cerebral+edema+and+functional+outcome+following+experimental+subarachnoid+hemorrhage.">Contribution of matrix metalloproteinase-9 to cerebral edema and functional outcome following experimental subarachnoid hemorrhage.</a> Cerebrovasc. Dis. 32, 289-295 (2011).</li></ol>

著者らは、開示することは何もありません。

SAH後の治療の選択肢が乏しいと、ほとんど効果のないです。したがって、ポスト出血性脳損傷の病態生理学は、更に、新たな治療標的を同定し、新規な治療アプローチを開発するために理解する必要がある。標準化された遺伝子改変動物、 すなわちマウス、でよく再現可能な動物モデルは、そのような調査のために重要である。それは密接にヒトでの病態生理に似ているようにCWPモ?...

SAHは、患者のための少なくとも有益な結果とストロークサブタイプである：患者の40％が出血1ヶ月後以内に死亡し、生存者はほとんど臨床的に良好な治療成績を持っていません。 自発SAHs（80％）の大部分は、主に動脈、脳底動脈および中大脳動脈（MCA）2を通信する前方および後方に沿って配置され、頭蓋内動脈瘤の破裂によって引き起こされる。 このような動脈瘤は、動物でモデル化することが困難であるため、SAHの動物モデルは、どちらかクモ膜下腔/脳室へ、またはくも膜下血管の血管内穿孔により血液の注射によって実施されています。 血液量が直接3を制御することができるように、大槽内へmagnaの自己血注入を行うことが容易で、再現可能である。残念ながら、SAHの病態生理のいくつかの側面には、 例えば血管損傷は、この手順によってモデル化することができない。 SAHの誘導のための別の技術的なアプローチは、槽内の静脈4の開口部である。 しかし、MCA支店で管腔内CWP、モデル、ヒトの病態生理最も密接5の手順であるように思われる。この方法は、Veelkenや同僚6,7によってBedersonらが、同時に開発され、最初のラットに記載されている。後で腔内穿孔モデルはマウス8,9に適合させた。フィラメントは、外頚動脈（ECA）に挿入し、内頸動脈（ICA）を介して頭蓋底に進む。 MCAの分岐点で、フィラメントは、血管を穿孔し、頭蓋底でクモ膜下腔への出血を誘発する。その後、血液は亀裂や血管に沿って残りのくも膜下空間内に分配する。出血は穿孔部位での血栓形成により停止したが、rebleedings、WHさICH、患者10にしばしば有害で発生する可能性があります。したがって、血管内のフィラメントモデルは、過去数年の間に広く使用されているSAHモデルとなりました。フィラメント穿孔モデル​​の最も頻繁に言及欠点は、出血量を直接制御することができず、従って、可変であり得ることである。この可変性は著しく動物生理学および後出血ICPを厳密に制御することによって低減することができる。 マウスは遺伝的に改変された株の大多数が利用可能であるという大きな利点を有する。しかしながら、それらの小さいサイズのために外科的処置は、より大きな種、 例えばラットまたはウサギにおけるよりも複雑になる傾向がある。従ってマウスにラットのために開発された技術の微細化は、しばしば、マウスは非常に限られた体重および血液量、血圧および血液ガス分析のための、並びにヘモグロビン飽和度と心拍数を監視するための非侵襲的な技術を持っている、例えば 、所望の結果をもたらさない可能な限り適用しなければならない。したがって、現在の出版物の目的は、マウスにおけるSAH用フィラメントミシンモデルを記述するために、このモデルは、標準化された再現性の高い方法で行うことができる方法を示すことです。

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

a murine model of subarachnoid hemorrhage

このビデオ公報にくも膜下出血（SAH）の標準化されたマウスモデルが提示されている。出血はウィリス穿孔（CWP）の血管内円で誘導され、頭蓋内圧（ICP）モニタリングによって証明されています。それによって動脈循環を取り囲むくも膜下スペースおよび小脳における亀裂均質な血液分布が達成される。体温、全身血圧、心拍数、およびヘモグロビン飽和度：動物生理学に挿管、機械的人工換気、及び種々の生理学的および心臓血管のパラメータの連続オンラインモニタリングによって維持される。それにより脳潅流圧が密に血管外遊出した血液の少ない可変容積をもたらすモニターすることができる。これは、マウスの血管内フィラメント穿孔のよりよい標準化を可能にし、モデル全体が高度に再現可能になります。したがって、野生型および遺伝での薬理学的および病態生理学的研究のために容易に利用可能であるLYマウ​​スを変えた。

死亡手術技術を習得したら手順は任意の術中死亡率を誘発しない。また、出血は、実質的に全ての動物において達成することができる。術後の死亡率は、ほとんどの動物が手術後（ 図5）1日目に死んで百分の30から40までです。 ICPはSAH後の値出血の前に、ICPは約4 mmHgである。 120 mmHgの、最大のICPの急激な増加をもたらす?...

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

A Murine Model of Subarachnoid Hemorrhage

ウィリス穿孔の管腔内サークルによるくも膜下出血の標準化されたマウスモデルが記載されている。血管穿孔やくも膜下出血は頭蓋内圧監視によって監視されています。さらに、種々の重要なパラメータが記録され、生理学的条件を維持するように制御される。

くも膜下出血のマウスモデル

In this video publication a standardized mouse model of subarachnoid  hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of  Willis ...

a-murine-model-of-subarachnoid-hemorrhage

Research

JoVE Journal

Medicine

19.5K ビュー.  University of Munich Medical Center. ウィリス穿孔の管腔内サークルによるくも膜下出血の標準化されたマウスモデルが記載されている。血管穿孔やくも膜下出血は頭蓋内圧監視によって監視されています。さらに、種々の重要なパラメータが記録され、生理学的条件を維持するように制御される。 

ビデオ: A Murine Model of Subarachnoid Hemorrhage

A Murine Model of Muscle Training by Neuromuscular Electrical Stimulation

Neuromuscular electrical stimulation (NMES) is a common clinical modality that is widely used to restore1, maintain2 or enhance3-5 muscle functional capacity. Transcutaneous surface stimulation of skeletal muscle involves a current flow between a cathode and an anode, thereby inducing excitement of the motor unit and the surrounding muscle fibers. 
NMES is an attractive modality to evaluate skeletal muscle adaptive responses for several reasons. First, it provides a reproducible experimental model in which physiological adaptations, such as myofiber hypertophy and muscle strengthening6, angiogenesis7-9, growth factor secretion9-11, and muscle precursor cell activation12 are well documented. Such physiological responses may be carefully titrated using different parameters of stimulation (for Cochrane review, see 13). In addition, NMES recruits motor units non-selectively, and in a spatially fixed and temporally synchronous manner14, offering the advantage of exerting a treatment effect on all fibers, regardless of fiber type. Although there are specified contraindications to NMES in clinical populations, including peripheral venous disorders or malignancy, for example, NMES is safe and feasible, even for those who are ill and/or bedridden and for populations in which rigorous exercise may be challenging. 
Here, we demonstrate the protocol for adapting commercially available electrodes and performing a NMES protocol using a murine model. This animal model has the advantage of utilizing a clinically available device and providing instant feedback regarding positioning of the electrode to elicit the desired muscle contractile effect. For the purpose of this manuscript, we will describe the protocol for muscle stimulation of the anterior compartment muscles of a mouse hindlimb.

A murine model of neuromuscular electrical stimulation (NMES), a safe and inexpensive clinical modality, to the anterior compartment muscles is described. This model has the advantage of modifying a readily available clinical device for the purpose of eliciting targeted and specific muscle contractions in mice.

神経筋電気刺激による筋力トレーニングのマウスモデル

Neuromuscular electrical stimulation (NMES) is a common clinical modality that is widely used to restore1, maintain2 or enhance3-5 muscle functional ...

医学

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

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

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

実験的くも膜下出血後の脳血管攣縮遅延を評価するための低死亡率のラットモデル

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

Murine Model of Wound Healing

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

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

創傷治癒のマウスモデル

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

A New Murine Model of Endovascular Aortic Aneurysm Repair

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

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

血管内大動脈瘤の修復の新しいマウスモデル

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

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

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

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

脳内出血のマウスモデルとして、自己血やクロストリジウムコラゲナーゼの線条体内注入

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

A Preclinical Murine Model of Hepatic Metastases

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

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

肝転移の前臨床マウスモデル

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

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

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

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

くも膜下出血の急性および後期後遺症の研究のためのウサギの血液シャントモデル：技術的側面

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

A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction

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

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

不可逆とリバーシブル片側尿管閉塞のマウスモデル

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

Pre-clinical Orthotopic Murine Model of Human Prostate Cancer

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

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

ヒト前立腺癌の前臨床同所性マウスモデル

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

Integrated Compensatory Responses in a Human Model of Hemorrhage

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

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