この作品は、アメリカ陸軍、医学研究および資材コマンド、戦闘死傷者ケアプログラムからの資金提供によってサポートされています。私たちはビデオを作るの彼らの援助のためにLTCケビン・S.エイカーズ、MDさんとクリステンR.ライに感謝します。

あらゆる人間の手続きの前に、治験審査委員会（IRB）は、プロトコルを承認する必要があります。この研究で使用されるプロトコルは、米陸軍医学研究および資材コマンドIRBによって承認されました。プロトコルは、制御され再現可能な実験室の設定で進行中の出血時の個人によって経験と同様の中央の血液量の漸進的減少を補償の生理学的応答を示すように設計されています。 25℃ - 実験室の室温は23で制御されています。 1.機器の準備<ol><li>機器やウォームアップや校正を必要とするデバイスの電源をオンにします。 注：装置およびデバイスは1Hzでデータを記録するデータ収集システムを含みます。非侵襲提供する2つの別個の装置、9-11二つの別個の赤外線フィンガーフォトプレチスモグラフィカフセンサを用いた上腕動脈の血圧および動脈酸素飽和度（SpO 2）の連続測定。 capnogra呼吸終期CO 2及び呼吸数を測定するためのpH;指パルスオキシメータは、代償予約を測定するために末梢拍動動脈波形を取得します。 </li><li>実験中の時間をマークするために使用される実験室のマスタークロックに合わせて、各機器にタイムスタンプを調整することにより、内部クロックとの楽器のすべてを同期します。 </li></ol> 2.件名の準備<ol><li>試験前にカフェイン、アルコール、および激しい運動24時間を回避するために、および血行動態代償は吐き気を誘発した場合には、プロトコルの前に少なくとも2時間を食べることを避けるために、被験者に指示します。 </li><li>プロトコルの開始前に、医師が被験者は最小限の健康要件を満たし、かつ除外基準（ニコチン使用、高血圧、自律神経機能障害、または失神のエピソードの歴史）が存在しないことを確実に保証するために、医療スクリーニング試験を行う必要があります。妊娠はの除外基準であるので、参加は、試験当日に、標準的な尿妊娠検査を取るために女性の参加を必要とします。 注：被験者の安全のため、研究医師が救命に認定されており、研究中に存在しています。設備の整った「クラッシュカートは意識の喪失またはLBNP手順中に起こる急性心臓不整脈が発生した場合に被験者の気道、呼吸、循環をサポートするためにすぐに利用可能です。 </li><li>手順については、被写体に通知し、研究に参加する書面による同意を得ます。 注：この研究の目的は、心血管代償（失神寸前の状態）の発症までLBNPを適用することで、被験者に説明してください。この点を定義する心血管パラメータがあることを説明し、これらの心血管パラメータが観察されたときにLBNPは終了します。彼らはまた、LBNPのproce時には標準で失神寸前の状態に関連する症状を経験する可能性があること主題を知らせますdure。これらの症状が発生し、LBNPを直ちに終了される場合は調査員に通知するために、被験者に指示します。 </li><li>主題のネオプレンLBNPスカートを置きます。スカートは、気密シールを作成するために、腰と胴体の周りにぴったりされていることを確認してください。 </li><li> LBNP中に所定の位置に胴体を確保するために、固定ポストを跨いLBNP室のベッドの上で仰向け築くために、被験者に指示します。 LBNP露光時に下半身を緩和する対象を指示します。室にベッドをスライドし、気密シールを作成するために、チャンバ開口部にネオプレンスカートを取り付けることにより、LBNP室に対象を固定します。 注：LBNP室は-100 mmHgの手動またはコンピュータ化されたプロファイルを持つに0からの内部の圧力を制御する（0.1 mmHgの範囲内）を正確の機能を提供します。チャンバは、被検者の身体の位置を固定するための調節可能なサドルを含みます。クリアプレキシガラスの窓は、被験者の脚の可視化を可能にします。調整可能なアルミ腰ボードは、対象と腸骨稜（ 図1）のレベルでLBNP室が着用ネオプレンスカートによって作成される気密シールを可能にします。 </li><li>場所の心電図（ECG）、左右の体液性鎖骨関節に、右側の電極と心拍数を連続的に測定するために修正されたリードIIの構成（ 図1）に下リブ（4の合計）を残しました。 </li><li>アームは手が心臓レベルでサポートされるように調整し、休符に被験者の腕を置きます。適切なサイズの指カフを使用して、赤外線フィンガーフォトプレチスモグラフィを配置します&#160;血圧の連続非侵襲ビート・ツー・ビート測定用左右の中指の装置。 </li><li>圧力モニタに指カフを取り付けます。製造業者の指示に従ってデバイスとレコード血圧を調整します。12は、被写体の情報を入力します（年齢、性別、heig必要であればModelflowアルゴリズムにより、ストローク量、心拍出量と末梢血管抵抗を計算するための適切な仮定（推定）を有効にするには、HT、および重量）。13,14 </li><li>補償引当金1,12（ 図2）の連続測定のための右の人差し指に指パルスオキシメータを配置します。 </li><li>被写体に鼻カニューレを配置し、吸気および呼気中の敏感な反射を確実にするために鼻から息をする対象を指示します。鼻空気サンプリングは、対象が症状を発症の自己申告のために自由に話をすることができます。呼吸の連続測定のためのカプノグラフに鼻カニューレを接続し、潮のCO 2を終了します。 </li></ol> 3. LBNPプロトコルを実行<ol><li>データ収集システムの「スタート」ボタンをクリックしてデータの記録を開始します。 5分間の録音基準データ。中央hypovoleの最初のレベルを開始します真空モータをオンにし、-15 mmHgの負圧を設定し、5分間この圧力を保持する。 図3は、プロトコルの概要を説明することによってミア。 </li><li> -30 mmHgのにLBNPを増やし、そして5分間この圧力を保持します。 </li><li> -45 mmHgのにLBNPを増やし、そして5分間この圧力を保持します。 </li><li> -60 mmHgのにLBNPを増やし、そして5分間この圧力を保持します。 </li><li> -70 mmHgのにLBNPを増やし、そして5分間この圧力を保持します。 </li><li> （-100 mmHgのLBNPで5分）プロトコルの終了または血行力学的代償不全の時点まで-10 mmHgで5分ごとによってLBNPレベルを増加し続けます。 LBNP室に圧力解除ボタンを押してLBNPを終了します。 注：血行動態代償は、80 mmHgの下の収縮期動脈圧の急落、またはそのようなグレーアウト（色覚の喪失）、トンネルビジョン、発汗、吐き気やめまい（ 図4）などのpresyncopal症状を報告する対象によって識別されます。 </li><li>LBNPの停止（postLBNP回復）後10分の間、データ収集システム上のデータを記録し続けます。 </li><li>データ取得システム上で「停止」ボタンをクリックすることで、10分間の回復期間の終了時にデータの記録を停止。 </li><li>被写体からすべての機器を外し、LBNP室から対象を削除します。研究室を離れる前に、彼らは無症状であることを確認するためにLBNPプラットフォームから退任した後に座って、被写体を確認して下さい。調査が完了しました。 </li><li>補償リザーブ指数（CRI）、平均動脈圧（MAP）、心拍数、およびのSpO 2値を抽出するための取得システムからデータファイルをダウンロードしてください。1,15,16 </li></ol>

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Trauma. 66, S69-S76 (2009).</li><li>Kragh, 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=Survival+with+emergency+tourniquet+use+to+stop+bleeding+in+major+limb+trauma.">Survival with emergency tourniquet use to stop bleeding in major limb trauma.</a> Ann Surgery. 249 (1), 1-7 (2009).</li><li>Chung, K. K., 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=Continous+renal+replacement+therapy+improves+survival+in+severly+burned+military+casualties+with+acute+kidney+injury.">Continous renal replacement therapy improves survival in severly burned military casualties with acute kidney injury.</a> J. Trauma. 64, S179-S187 (2008).</li><li>Stewart, C. 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=The+compensatory+reserve+for+early+and+accurate+prediction+of+hemodynamic+compromise:+case+studies+for+clinical+utility+in+acute+care+and+physical+performance.">The compensatory reserve for early and accurate prediction of hemodynamic compromise: case studies for clinical utility in acute care and physical performance.</a> J Special Op. Med. 16, 6-13 (2016).</li></ol>

The authors declare that they have no competing financial interests. The views expressed herein are the private views of the authors and are not to be construed as representing those of the US Department of the Army or the US Department of Defense.

中央の血液量の漸進的かつ継続的な減少を引き起こすLBNPを使用して、我々は低血圧や徐脈（ 図7）の突然の発症によって特徴づけられる被験者における血行動態代償不全の典型的な応答を誘導することができました。出血に統合された代償性反応が非常に複雑であることを理解することが重要である19は、血液の損失に対する耐性が大幅に個体差が生じる。他の人が同様?...

心臓血管系の最も重要な機能は、動脈血圧の恒常性の調節を介して身体のすべての組織に十分な灌流（血流および酸素送達）の制御です。補償（ 例えば 、自律神経系の活動、心拍数と収縮、静脈還流、血管収縮、呼吸）の様々なメカニズムが、組織内の酸素の正常な生理的レベルを維持するために貢献しています。そのような出血によって引き起こされるもののような循環血液量での1削減が妥協することができます心血管代償機構の能力、最終的には致命的なことができ、低動脈血圧、深刻な組織低酸素症、及び循環性ショックにつながります。 重度の出血（ すなわち、出血性ショック）によって引き起こされる循環性ショック、外傷による死亡の主な原因である。ショックの発症から患者を防ぐ最も挑戦的な側面の2つが私たちですその早期発症を認識することができません。ショックの開発に向けた進行の早期および正確な評価は、現在あるため、体の多数の代償の血液損失の初期段階ではほとんど変更バイタルサインの測定値を提供する技術（ すなわち、医療モニター）により、臨床設定で制限されています血圧を調節するための機構。3-6このように、血液の損失を補償するために、身体の準備の合計を測定する能力は、組織灌流状態とショックを発症するリスクの最も正確な反射を表す。1この予備が呼び出され正確に動脈波形の特徴の変化をリアルタイムで測定することにより評価することができる補償引当金補償引当金の1枯渇は、低血圧の突然の発症と重症患者で観察され、端末心血管不安定性を複製します。;血行動態デコとして知られている状態mpensation。7 ヒトにおける進行中の失血中代償準備および血圧の調節の使用との関係は（生理学的測定の包括的なセットを使用して実験室で実証することができ、例えば 、血圧、心拍数、動脈血酸素飽和度、一回拍出量、出血中に発生したものと同様の中央の血液量の継続的な進歩的な削減の際に、標準的な生理学的モニタリングによって提供さ心拍出量、血管抵抗、呼吸数、パルスの文字、精神状態、呼吸終期CO 2、組織の酸素）。下げ中心血液量が下半身陰圧（LBNP）の漸進的増加で非侵襲的に誘導することができる。8生理学的測定とLBNPのこの組み合わせを使用して、縮小中心血液量を補償する身体能力を評価する方法の概念理解を容易にすることができます悪魔trated。この研究はprelab準備、シミュレートされた出血中に他の生理学的反応に関連した代償性反応のデモンストレーション、および結果のpostlab評価を示しています。補償引当金の測定を行うために必要な実験技術は、ヒトのボランティアで実証されています。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Dynamic Research Evaluation Workstation (DREW) data acquisition syetem</td>
			<td>NA</td>
			<td>NA</td>
			<td>Custom Built by ISR personnel.&#160; The DREW allows for time synchronization of both digital and analog signal data collection from up to 16 independent instruments with a sampling rate of 1000 Hz.</td>
		</tr>
		<tr>
			<td>Finometer</td>
			<td>Finapress Medical Systems (FMS)</td>
			<td>Model 1</td>
			<td>Device that provides non-invasive, continuous measurements of brachial artery blood pressure and arterial oxygen saturation (SpO2) using two separate infrared finger photophlethymography cuff sensors.</td>
		</tr>
		<tr>
			<td>BCI Capnocheck Plus</td>
			<td>Smith Medical PM Inc.</td>
			<td>9004</td>
			<td>Capnograph used to measure&#160; end tidal CO2 and respiration rate</td>
		</tr>
		<tr>
			<td>CipherOX&#160;</td>
			<td>Flashback Technologies Inc.</td>
			<td>R200</td>
			<td>Investigational device used to calculate Compensatory Reserve Index (CRI)</td>
		</tr>
		<tr>
			<td>Nonin 9560 Pulse Oximeter</td>
			<td>Nonin</td>
			<td>9560</td>
			<td>finger pulse oximeter</td>
		</tr>
		<tr>
			<td>Lower Body Negative Pressure Chamber (LBNP)</td>
			<td>NASA</td>
			<td>79K32632-1</td>
			<td>Custom Chamber built by NASA</td>
		</tr>
		<tr>
			<td>ECG Biotach</td>
			<td>Gould</td>
			<td>13-6615-65</td>
			<td>Electrocardiograph for measuring ECG</td>
		</tr>
		<tr>
			<td>Nasal CO2 Sample Line</td>
			<td>Salter Labs</td>
			<td>REF 4000</td>
			<td>Latex free nasal cannula for sampling expired air</td>
		</tr>
	</tbody>
</table>

integrated compensatory responses in a human model of hemorrhage

出血は、血液の損失の重大性の早期診断が困難である理由の一つ、トラウマに関連した死亡の主な原因です。現在の臨床ツールが原因代償機構に出血の初期段階で安定したままでバイタルサインの対策を提供するため、出血患者の評価は困難です。従って、減少循環血液量と、それらがどのように進行中の進行性の出血中に変化を補償するためのメカニズムの合計統合を理解し、測定する必要があります。身体の準備金は減少し、循環血液量を補償するための「補償引当金」と呼ばれています。補償金は正確に高性能のコンピュータを使用して測定された動脈波形の特徴の変化のリアルタイム測定を用いて評価することができます。下半身陰圧（LBNP）は、出血に関連したヒトにおける生理学的反応の多くをシミュレートすることが示されていますそして、出血に対する代償応答を研究するために使用されます。本研究の目的は、出血のシミュレーションとしてLBNPと中央の血液量の漸進的な削減の際に評価される方法を補償引当金を実証することです。

LBNP手順は胴体下部と脚周りの空気圧の低下を引き起こします。この真空が漸進的に増加すると、下半身に頭と胴体上部からの血液量の変化は、中心血液量減少の状態を作成します。中央の血液量（ すなわち 、LBNP）の漸進的な減少は、赤外指の光電脈波（ 図5）を用いて測定した動脈波形の特徴で有意な変化を生成します。補償準備指数（CRI）は?...

Watch this Scientific Journal Video about Integrated Compensatory Responses in a Human Model of Hemorrhage at JoVE.com

Integrated Compensatory Responses in a Human Model of Hemorrhage

このプロトコルの目的は、ヒトの血液量不足の代償機構の合計積分を定量化するために使用することができる人間の出血の非侵襲的な実験モデルとして下半身陰圧を用いて還元中央の血液量に対する代償応答を測定するための技術を実証することです。

出血の人体モデルで統合代償応答

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

integrated-compensatory-responses-in-a-human-model-of-hemorrhage

Research

JoVE Journal

Medicine

12.4K ビュー.  JBSA Fort Sam Houston. このプロトコルの目的は、ヒトの血液量不足の代償機構の合計積分を定量化するために使用することができる人間の出血の非侵襲的な実験モデルとして下半身陰圧を用いて還元中央の血液量に対する代償応答を測定するための技術を実証することです。 

ビデオ: Integrated Compensatory Responses in a Human Model of Hemorrhage

Stem Cell Transplantation in an in vitro Simulated Ischemia/Reperfusion Model

Stem cell transplantation protocols are finding their way into clinical practice1,2,3. Getting better results, making the protocols more robust, and finding new sources for implantable cells are the focus of recent research4,5. Investigating the effectiveness of cell therapies is not an easy task and new tools are needed to investigate the mechanisms involved in the treatment process6. We designed an experimental protocol of ischemia/reperfusion in order to allow the observation of cellular connections and even subcellular mechanisms during ischemia/reperfusion injury and after stem cell transplantation and to evaluate the efficacy of cell therapy. H9c2 cardiomyoblast cells were placed onto cell culture plates7,8. Ischemia was simulated with 150 minutes in a glucose free medium with oxygen level below 0.5%. Then, normal media and oxygen levels were reintroduced to simulate reperfusion. After oxygen glucose deprivation, the damaged cells were treated with transplantation of labeled human bone marrow derived mesenchymal stem cells by adding them to the culture. Mesenchymal stem cells are preferred in clinical trials because they are easily accessible with minimal invasive surgery, easily expandable and autologous. After 24 hours of co-cultivation, cells were stained with calcein and ethidium-homodimer to differentiate between live and dead cells. This setup allowed us to investigate the intercellular connections using confocal fluorescent microscopy and to quantify the survival rate of postischemic cells by flow cytometry. Confocal microscopy showed the interactions of the two cell populations such as cell fusion and formation of intercellular nanotubes. Flow cytometry analysis revealed 3 clusters of damaged cells which can be plotted on a graph and analyzed statistically. These populations can be investigated separately and conclusions can be drawn on these data on the effectiveness of the simulated therapeutical approach.

Stem Cell Transplantation in an in vitro Simulated Ischemia/Reperfusion Model

We demonstrate how to set up an in vitro ischemia/reperfusion model and how to evaluate the effect of stem cell therapy on postischemic cardiac cells.

における幹細胞移植 in vitroで模擬虚血/再灌流モデル

Stem cell transplantation protocols are finding their way into clinical practice1,2,3. Getting better results, making the protocols more robust, and ...

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) ...

A Murine Model of Subarachnoid Hemorrhage

In this video publication a standardized mouse model of subarachnoid hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of Willis perforation (CWp) and proven by intracranial pressure (ICP) monitoring. Thereby a homogenous blood distribution in subarachnoid spaces surrounding the arterial circulation and cerebellar fissures is achieved. Animal physiology is maintained by intubation, mechanical ventilation, and continuous on-line monitoring of various physiological and cardiovascular parameters: body temperature, systemic blood pressure, heart rate, and hemoglobin saturation. Thereby the cerebral perfusion pressure can be tightly monitored resulting in a less variable volume of extravasated blood. This allows a better standardization of endovascular filament perforation in mice and makes the whole model highly reproducible. Thus it is readily available for pharmacological and pathophysiological studies in wild type and genetically altered mice.

A standardized mouse model of subarachnoid hemorrhage by intraluminal Circle of Willis perforation is described. Vessel perforation and subarachnoid bleeding are monitored by intracranial pressure monitoring. In addition various vital parameters are recorded and controlled to maintain physiologic conditions.

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 ...

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As such, primary or &#39;neuronal-like&#39; cell culture systems are commonly utilized. While&#160;these systems are relatively easy to work with, and are useful model systems in which various functional outcomes (such as cell death) can be readily quantified, the examined outcomes and pathways in cultured immature neurons (such as excitotoxicity-mediated cell death pathways) are not necessarily the same as those observed in mature brain, or in intact tissue. Therefore, there is the need to develop models in which cellular mechanisms in mature neural tissue can be examined. We have developed an in vitro technique that can be used to investigate a variety of molecular pathways in intact nervous tissue. The technique described herein utilizes rat cortical tissue, but this technique can be adapted to use tissue from a variety of species (such as mouse, rabbit, guinea pig, and chicken) or brain regions (for example, hippocampus, striatum, etc.). Additionally, a variety of stimulations/treatments can be used (for example, excitotoxic, administration of inhibitors, etc.). In conclusion, the brain slice model described herein can be used to examine a variety of molecular mechanisms involved in excitotoxicity-mediated brain injury.

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

We have developed a brain slice model which can be used to examine molecular mechanisms involved in excitotoxicity-mediated brain injury.&#160;This technique generates viable mature brain tissue and reduces animal numbers required for experimentation, whilst keeping the neuronal circuitry, cellular interactions, and postsynaptic compartments partly intact.

脳Microslicesの興奮毒性刺激<em&gt;インビトロ</em&gt;脳卒中のモデル

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As ...

Urinary Bladder Distention Evoked Visceromotor Responses as a Model for Bladder Pain in Mice

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized by increased urgency and frequency of urination, as well as nocturia and general pelvic pain, especially upon bladder filling or voiding. Despite years of research, the cause of IC/BPS remains elusive and treatment strategies are unable to provide complete relief to patients. In order to study nervous system contributions to the condition, many animal models have been developed to mimic the pain and symptoms associated with IC/BPS. One such murine model is urinary bladder distension (UBD). In this model, compressed air of a specific pressure is delivered to the bladder of a lightly anesthetized animal over a set period of time. Throughout the procedure, wires in the superior oblique abdominal muscles record electrical activity from the muscle. This activity is known as the visceromotor response (VMR) and is a reliable and reproducible measure of nociception. Here, we describe the steps necessary to perform this technique in mice including surgical manipulations, physiological recording, and data analysis. With the use of this model, the coordination between primary sensory neurons, spinal cord secondary afferents, and higher central nervous system areas involved in bladder pain can be unraveled. This basic science knowledge can then be clinically translated to treat patients suffering from IC/BPS.

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized in part by pelvic pain. In order to study nervous system contributions to the condition, a physiological model of urinary bladder pain is used in mice and rats.

マウスの膀胱痛に対するモデルとしての膀胱膨満誘発内臓運動応答

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition ...

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 ...

Mouse Pneumonectomy Model of Compensatory Lung Growth

In humans, disrupted repair and remodeling of injured lung contributes to a host of acute and chronic lung disorders which may ultimately lead to disability or death. Injury-based animal models of lung repair and regeneration are limited by injury-specific responses making it difficult to differentiate changes related to the injury response and injury resolution from changes related to lung repair and lung regeneration. However, use of animal models to identify these repair and regeneration signaling pathways is critical to the development of new therapies aimed at improving pulmonary function following lung injury. The mouse pneumonectomy model utilizes compensatory lung growth to isolate those repair and regeneration signals in order to more clearly define mechanisms of alveolar re-septation. Here, we describe our technique for performing mouse pneumonectomy and sham pneumonectomy. This technique may be utilized in conjunction with lineage tracing or other transgenic mouse models to define molecular and cellular mechanism of lung repair and regeneration.

Mouse pneumonectomy is a commonly employed model of compensatory lung growth. This procedure can be used in conjunction with lineage tracing or transgenic mouse models to elucidate underlying mechanisms.

代償肺の成長のマウス肺モデル

In humans, disrupted repair and remodeling of injured lung contributes to a host of acute and chronic lung disorders which may ultimately lead to ...

Induction of Accelerated Atherosclerosis in Mice: The "Wire-Injury" Model

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. Moreover, by rupture of the defective vascular wall, atherosclerosis induces occlusive thrombus formation, which represents the main cause of myocardial infarction or stroke and the most frequent cause of death. Despite the advances in the cardiovascular field, many questions remain unanswered, and additional basic research is essential to improve our understanding of the molecular mechanisms during atherosclerosis and its effects. Due to limited clinical studies, there is a need for representative animal models recreating atherosclerotic conditions such as neointima formation after stent implantation, balloon angioplasty, or endarterectomy. Since the mouse presents many advantages and is the most frequently used model for studying molecular processes, the current study proposes an invasive procedure of endothelial denudation, also known as the wire-injury model, which is representative of the human condition of neointima formation in arteries after revascularization procedures.

This study describes an invasive procedure for the induction of accelerated atherosclerosis in mice. In comparison to other methods using electric- or cryo-induced injury, mechanical-induced injury mimics the human condition of restenosis after revascularization therapies and is ideal for the study of the molecular mechanisms involved.

マウスにおける加速アテローム性動脈硬化症の誘導:ワイヤー傷害モデル

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

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

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

ワイヤー図法を使用してマウスの腸間膜動脈の等尺性収縮力測定

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

A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the pathophysiological mechanism and to develop effective therapeutic strategy for this devastating neurological disorder. Intraparenchymal hemorrhage and post-traumatic inflammatory response induced by initial physical impact can aggravate microglia/macrophage activation and neuroinflammation which subsequently worsen brain pathology. We provide here a controlled cortical impact (CCI) protocol that can reproduce experimental cortical contusion in mice by using a pneumatic impactor system to deliver mechanical force with controllable magnitude and velocity onto the dural surface. This preclinical model allows researchers to induce moderately severe focal cerebral contusion in mice and to investigate a wide range of post-traumatic pathological progressions including hemorrhage contusion, microglia/macrophage activation, iron toxicity, axonal injury, as well as short-term and long-term neurobehavioral deficits. The present protocol can be useful for exploring the long-term effects of and potential interventions for cerebral contusion.

<meta charset="utf8"></head><body>外傷性出血挫傷および神経炎症に対する前臨床制御皮質衝撃モデル

Intraparenchymal hemorrhage and neuroinflammation accompanied by cerebral contusion can trigger severe secondary brain injury. This protocol details a mouse controlled cortical impact (CCI) model allowing researchers to study hemorrhage contusion and post-traumatic immune responses and explore potential therapeutics.