著者には謝辞はありません。

このプロトコールは、ソウル大学分立病院動物実験センターの承認を受けた。動物のケアおよび実験は、実験動物のケアおよび使用のための米国国立衛生研究所のガイドラインに従って行われた。 1.外科的準備<ol><li>手術の前に、開存性を確実にするために滅菌生理食塩水でカテーテルを洗い流す。 </li><li>手術用テーブルに暖房用毛布を置き、無菌ドレープでテーブルを覆う。 </li><li>雄Sprague-Dawleyラット（270-330g）を、100％酸素中3.0％〜4.0％のイソフルランを含むアクリルボックスに入れる。 </li><li>ラットの目に潤滑剤を塗布する。 </li><li>ラットを仰臥位の手術台に置き、吸入イソフルラン（1.0％〜2.5容積％）を連続的に投与したフェイシャルマスクを用いて麻酔を維持する。 </li><li>直腸プローブを配置し、体温を37.0〜38.0℃の間で監視および維持する。 </li&gt; </ol> 2.大腿動脈カテーテル法<ol><li>右の鼠径部をベタディンと70％エタノールを使って静かにこすります。 </li><li>右鼠径部のはさみを使って、2cmの水平な皮膚切開を行います。 </li><li>開創器を使用して、手術野を露出させる。 </li><li>周囲の静脈および神経から大腿動脈を解剖する。湾曲した鉗子と鈍い鉗子を使用して、動脈の1cmの部分を分離する。 </li><li> 4.0黒い絹の縫合糸を使用して、暴露を最大にするために、動脈の近位端および遠位端の両方に緩い結び目を置く。 </li><li>大腿動脈をマイクロはさみで切開する。 </li><li> 2-Frを挿入します。マイクロ鉗子を用いて大腿動脈内にバルーンチップカテーテルを挿入した。近位結紮でカテーテルヘッドから約1cmのところでカテーテルを血管に固定し、遠位結紮糸を結ぶ。 </li></ol> 3.頚動脈カテーテル法<ol><li> betadを使用して右前頸部を擦るineと70％エタノールを入れ、皮膚切開を行います。 </li><li>開創器を使用して、手術野を露出させる。動脈の1cmの部分を分離し、暴露を最大にするために、動脈の近位端および遠位端の両方に絹の縫合糸を用いて緩く結ぶ。 </li><li> 24 Gの静脈内カテーテルを用いて頸動脈を穿刺し、カテーテルの近位1cmを心臓に向けて前進させる。 </li><li>近位結紮でカテーテルを固定し、遠位結紮糸を結ぶ。 </li><li>三方活栓を使用して、カテーテルの遠位端を生理食塩水で満たされたマイクロチューブおよび外部リザーバーに接続する。 </li></ol> 4.尾部動脈カテーテル法<ol><li>ベタディンと70％エタノールを使用して尾の腹側を擦り、2cmの皮膚切開を行います。 </li><li>周囲の構造から尾動脈を解剖し、湾曲鉗子と鈍端鉗子を用いて動脈の1cm切片を分離する。 </li><li> 4.0黒の絹の縫合糸を使用して、緩く置く暴露を最大限にするために動脈の近位端および遠位端の両方を結ぶ。 </li><li> 24 Gの静脈内カテーテルを用いて尾動脈を突き刺し、カテーテルを動脈内に進める。 </li><li>近位の結紮具でカテーテルを血管（カテーテルヘッドから約1cm）に固定し、遠位結紮糸を結ぶ。 </li><li>カテーテルの遠位部分を動脈圧監視装置に接続する。 </li></ol> 5.脊髄虚血の誘導<ol><li>カテーテル挿入が完了したら、2 Fr.を進める。カテーテルの先端が左鎖骨下動脈に達するように、バルーンチップカテーテルを下降する胸部大動脈に挿入する。 </li><li>挿入部位から10 cmの深さまで挿入します。 </li><li> 100ユニット/ mLの濃度の150単位のヘパリンを頸動脈カテーテルに注入する。 </li><li> 0.05mLの生理食塩水でカテーテルバルーンを膨らませる。 </li><li>同時に、血液を外部血液コンテナにcか​​ら排出させる近位動脈圧を80mmHgに調節するための頚動脈動脈。 </li><li>動脈圧モニタリングシステムを3方向ストップコックの残りの管腔に接続し、動脈圧を監視して排液量を制御する。 </li><li>突然の減少と遠位動脈圧の連続的な損失によって、大動脈閉塞の成功を確認する。 </li><li> 9、10、または11分の大動脈閉塞の後、Fogartyカテーテルバルーンを収縮させ、排出された血液を再注入する。 </li></ol> 6.手術後のケアおよび神経学的評価<ol><li>尾動脈を通る動脈圧を監視しながら、大腿動脈および頸動脈からカテーテルを取り出し、絹の縫合糸で創傷を閉じる。 </li><li>動脈圧が正常範囲に回復したことを確認した後、尾動脈からカテーテルを取り出し、創傷を閉じる。 </li><li>麻酔から回復した後、ラットをケージに戻す。 </li><li>評価する手術後24時間で運動不足指数を用いて肢体運動機能を評価した（ 表1 ）。運動不足指数は、歩行スコアと配置/歩行反射スコアの合計として定義される。 6のモーター赤字指数は最大赤字を示します。 </li></ol> 7.組織病理学的評価<ol><li>神経学的評価後、ラットをマスク送達イソフルランで麻酔し、麻酔下でヘパリン処理された生理食塩水100mLで心筋灌流によりそれらを屠殺し、脊髄を抽出する。 8 </li><li>パラフィンに腰椎3-5のレベルからコードセクションを埋め込みます。 </li><li>ヘマトキシリンおよびエオシン（H＆E）で横断切片を染色する。 </li><li>顕微鏡下での運動ニューロン損傷を観察する。 9 </li></ol> 8.統計分析<ol><li> Social Sciencesバージョン20の統計パッケージを使用して統計分析を実行します。モータdefKruskal-Wallis検定、続いてMann-Whitney U検定を用いて、3つの群の奏功指数を比較した。 0.05未満のP値は統計的に有意であると考えられた。 </li></ol>

<ol>
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著者には競合する金銭的利益はない。この研究は、韓国政府の国立研究財団からの助成金2012R1A1A3014010によって支援された。

今回の研究では、大動脈閉塞時間に依存して後肢に様々な程度の運動障害を誘発するTaira and Marsalaの方法5に基づく脊髄虚血のラットモデルを実証した。 大動脈閉塞の長さは、運動不足の程度に影響し得る。大動脈閉塞時間が長い場合、運動障害はより深刻になる。したがって、研究者は、このモデルで大動脈閉塞時間を制御することによって、ある程?...

対麻痺は、胸腹部大動脈瘤手術の致命的な合併症である。これは、大動脈のクロスクランプおよびアンクランプ中に起こる脊髄虚血 - 再灌流損傷に起因する。怪我の影響を受けて全身低体温症と脳脊髄ドレナージ脊髄を保護するために導入されている、2、3、4しかし、多くの患者が残っているなど、1つのいくつかの戦略。 いくつかの動物の脊髄虚血モデルがその病因を調査し、損傷に対する防御戦略を考案するために導入されている。今回の研究では、平良とマルサラの方法に基づいた脊髄虚血のラットモデルを概説する。サイズに多少の違いはあるものの5ラットにおける脊髄循環システムは、ヒトでの脊髄の血管および担保システムに非常に類似しており、ロケーション。 図6、 図7はこのように、ラットは、病因、合併症、および脊髄虚血の治療を調査する実験モデルのために利用する解剖学的に適切な動物です。さらに、この脊髄虚血モデルは、胸部大動脈の血管内バルーン閉塞を利用することにより最小限の介入で確実な大動脈閉塞を生じる。 本研究では、この脊髄虚血ラットモデルが、大動脈閉塞時間に応じて重症度が異なる後肢における再現性運動障害を誘発することを実証した。

<table border="0" cellpadding="0" cellspacing="0" width="1009">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:269px;">Fogarty Arterial Embolectomy catheter</td>
			<td style="width:181px;">Edward Life Sciences</td>
			<td style="width:147px;">120602F</td>
			<td style="width:413px;">a balloon-tipped catheter inserted into the femoral artery</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:269px;">BD Insyte-N Autoguard Shielded IV catheter&#160;</td>
			<td style="width:181px;">BD&#160;</td>
			<td style="width:147px;">381411</td>
			<td>24-gauge intravenous catheter</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">50mL syringe</td>
			<td style="width:181px;">KOREA VACCINE&#160;</td>
			<td>KOVAX-SYRINGE 50mL</td>
			<td>Facial mask</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">1mL syringe</td>
			<td style="width:181px;">KOREA VACCINE</td>
			<td>KOVAX-SYRINGE 1ml</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:269px;">Recal probe</td>
			<td>HARVARD APPARATUS</td>
			<td>50-7221F</td>
			<td>Rectal probe for temperature monitoring</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Micro dissecting spring scissor</td>
			<td>Jeung do bio &#38; Plant co.LTD.</td>
			<td>JD-S-10</td>
			<td>Micro-scissor</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">SCISSOR (SHARP-SHARP)</td>
			<td>Jeung do bio &#38; Plant co.LTD.</td>
			<td>S-51-12-S</td>
			<td>Scissors</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Retractor</td>
			<td>Jeung do bio &#38; Plant co.LTD.</td>
			<td>JD-S-74A</td>
			<td>Retractor</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Micro forcep&#160;</td>
			<td>Jeung do bio &#38; Plant co.LTD.</td>
			<td>JD-S-29</td>
			<td>Micro-forceps</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:269px;">MOSQUITO FORCEP (Curved)</td>
			<td>Jeung do bio &#38; Plant co.LTD.</td>
			<td>S-44-CPK</td>
			<td>Curved forceps</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">DRESSING FORCEP&#160;</td>
			<td>Jeung do bio &#38; Plant co.LTD.</td>
			<td>S-37-16S</td>
			<td>Blunted forceps</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">4/0 black silk&#160;</td>
			<td>Woori Medical</td>
			<td style="width:147px;">S431</td>
			<td>4.0 black silk suture</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">3-WAY STOCK</td>
			<td style="width:181px;">Seonwon Medcal</td>
			<td>D-98-01</td>
			<td>3-way stopcock</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Patient monitor</td>
			<td>PHILIPS</td>
			<td style="width:147px;">MP20</td>
			<td>The arterial pressure monitoring device.&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Heating blanket</td>
			<td style="width:181px;">Self production</td>
			<td style="width:147px;"></td>
			<td>Heating blanket</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Microtube and external reservoir</td>
			<td style="width:181px;">Self production</td>
			<td style="width:147px;"></td>
			<td>Microtube and external reservoir</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Heparin</td>
			<td style="width:181px;">JW Pharmaceutical</td>
			<td style="width:147px;"></td>
			<td>Heparin</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">0.9% NS 1000ml</td>
			<td style="width:181px;">JW Pharmaceutical</td>
			<td style="width:147px;"></td>
			<td>Normal saline</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Isoflurane</td>
			<td style="width:181px;">Hana Med</td>
			<td style="width:147px;"></td>
			<td>Isoflurane</td>
		</tr>
	</tbody>
</table>

reproducible motor deficit following aortic occlusion in a rat model of spinal cord ischemia

<html>脊髄虚血は、胸腔腹部大動脈瘤手術後の致命的な合併症である。研究者は、脊髄虚血の実験モデルを用いてこの合併症を予防および治療するための戦略を調査することができる。ここに記載されたモデルは、ラットの脊髄虚血モデルにおける胸部大動脈閉塞後の閉塞の長さに関連する様々な程度の対麻痺を示す。 2-Fr。バルーン先端カテーテルを、麻酔した雄Sprague-Dawleyラットの左鎖骨下動脈にカテーテル先端を配置するまで、大腿動脈を通して下行胸部大動脈に前進させた。カテーテルバルーンを膨張させることによって脊髄虚血を誘発した。一定の閉塞（9,10または11分）後、バルーンは収縮した。手術後24時間で運動異常を用いて神経学的評価を行い、病理組織学的検査のために脊髄を採取した。 10分の大動脈閉塞を受けたラットは、中程度ではあるが可逆的な運動障害を示した。大動脈閉塞の11分間に曝されたラットは、完全で持続的であった大動脈閉塞の期間がより短いラットにおいて、脊髄切片における運動ニューロンはより保存された。 研究者は、この脊髄虚血モデルを用いて胸部大動脈閉塞後に再現性のある後肢運動障害を達成することができる。

脊髄虚血の期間中、大動脈閉塞を9分（n = 3）、10分（n = 3）、または11分（n = 3）行った。ラットにおける運動障害指数を表2に示す。大動脈閉塞を9分間受けたラットは、後肢に軽度の可逆性運動障害を示した。 10分間の大動脈閉塞を受けたラットは、中等度の運動障害を示したが、完全な麻痺はなかった。 11分の閉塞時間を経たラットは、完全で持続的な麻痺を示した。 ...

Watch this Scientific Journal Video about Reproducible Motor Deficit Following Aortic Occlusion in a Rat Model Of Spinal Cord Ischemia at JoVE.com

Reproducible Motor Deficit Following Aortic Occlusion in a Rat Model Of Spinal Cord Ischemia

この研究は、ラットにおいて最小侵襲性で容易に再現可能な脊髄虚血モデルを作製する技術を実証している。大動脈閉塞時間を制御することにより、様々な程度の後肢運動欠損を生じさせることができる。

脊髄虚血ラットモデルにおける大動脈閉塞後の再現性のある運動障害

Spinal cord ischemia is a fatal complication following thoracoabdominal aortic aneurysm surgery. Researchers can investigate the strategies for preventing ...

reproducible-motor-deficit-following-aortic-occlusion-rat-model

Research

JoVE Journal

Medicine

7.1K ビュー.  SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul. この研究は、ラットにおいて最小侵襲性で容易に再現可能な脊髄虚血モデルを作製する技術を実証している。大動脈閉塞時間を制御することにより、様々な程度の後肢運動欠損を生じさせることができる。 

ビデオ: Reproducible Motor Deficit Following Aortic Occlusion in a Rat Model Of Spinal Cord Ischemia

Acute and Chronic Tactile Sensory Testing after Spinal Cord Injury in Rats

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory testing in rat SCI models is needed. However, until recently, no single testing approach had been validated for SCI so that standardized methods have not been implemented across labs. Additionally, available testing methods could not be implemented acutely or when severe motor impairments existed, preventing studies of the development of SCI-induced allodynia3. Here we present two validated sensory testing methods using von Frey Hair (VFH) monofilaments which quantify changes in tactile sensory thresholds after SCI4-5. One test is the well-established Up-Down test which demonstrates high sensitivity and specificity across different SCI severities when tested chronically5. The other test is a newly-developed dorsal VFH test that can be applied acutely after SCI when allodynia develops, prior to motor recovery4-5. Each VFH monofilament applies a calibrated force when touched to the skin of the hind paw until it bends. In the up-down method, alternating VFHs of higher or lower forces are used on the plantar L5 dermatome to delineate flexor withdrawal thresholds. Successively higher forces are applied until withdrawal occurs then lower force VFHs are used until withdrawal ceases. The tactile threshold reflects the force required to elicit withdrawal in 50% of the stimuli. For the new test, each VFH is applied to the dorsal L5 dermatome of the paw while the rat is supported by the examiner. The VFH stimulation occurs in ascending order of force until at least 2 of 3 applications at a given force produces paw withdrawal. Tactile sensory threshold is the lowest force to elicit withdrawal 66% of the time. Acclimation, testing and scoring procedures are described. Aberrant trials that require a retest and typical trials are defined. Animal use was approved by Ohio State University Animal Care and Use Committee.

We describe two tactile sensory testing methods for acute or chronic periods of spinal cord injury in rats. These validated procedures can detect the development and maintenance of allodynia-like sensations.

ラット脊髄損傷後の急性および慢性の触覚官能検査

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory ...

医学

A Contusion Model of Severe Spinal Cord Injury in Rats

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is described to obtain a consistent model of severe SCI. Use of a stereotactic frame and computer controlled impactor allows for creation of reproducible injury. Hypothermia and urinary tract infection pose significant challenges in the post-operative period. Careful monitoring of animals with daily weight recording and bladder expression allows for early detection of post-operative complications. The functional results of this contusion model are equivalent to transection models. The contusion model can be utilized to evaluate the efficacy of both neuroprotective and neuroregenerative approaches.

A contusion model of severe spinal cord injury is described. Detailed pre-operative, operative and post-operative steps are described to obtain a consistent model.

ラットにおける重度の脊髄損傷挫傷モデル

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is ...

2-Vessel Occlusion/Hypotension: A Rat Model of Global Brain Ischemia

Cardiac arrest followed by resuscitation often results in dramatic brain damage caused by ischemia and subsequent reperfusion of the brain. Global brain ischemia produces damage to specific brain regions shown to be highly sensitive to ischemia 1. Hippocampal neurons have higher sensitivity to ischemic insults compared to other cell populations, and specifically, the CA1 region of the hippocampus is particularly vulnerable to ischemia/reperfusion 2.
The design of therapeutic interventions, or study of mechanisms involved in cerebral damage, requires a model that produces damage similar to the clinical condition and in a reproducible manner. Bilateral carotid vessel occlusion with hypotension (2VOH) is a model that produces reversible forebrain ischemia, emulating the cerebral events that can occur during cardiac arrest and resuscitation. We describe a model modified from Smith et al. (1984) 2, as first presented in its current form in Sanderson, et al. (2008) 3, which produces reproducible injury to selectively vulnerable brain regions 3-6. The reliability of this model is dictated by precise control of systemic blood pressure during applied hypotension, the duration of ischemia, close temperature control, a specific anesthesia regimen, and diligent post-operative care. An 8-minute ischemic insult produces cell death of CA1 hippocampal neurons that progresses over the course of 6 to 24 hr of reperfusion, while less vulnerable brain regions are spared. This progressive cell death is easily quantified after 7-14 days of reperfusion, as a near complete loss of CA1 neurons is evident at this time.
In addition to this brain injury model, we present a method for CA1 damage quantification using a simple, yet thorough, methodology. Importantly, quantification can be accomplished using a simple camera-mounted microscope, and a free ImageJ (NIH) software plugin, obviating the need for cost-prohibitive stereology software programs and a motorized microscopic stage for damage assessment.

Bilateral carotid occlusion coupled with systemic hypotension produces global brain ischemia in the rat, resulting in damage to the hippocampus with reproducible severity. Animal subjects are impaired with predictable patterns of brain damage, they recover expediently, and mortality rates are comparatively low.

2血管閉塞/低血圧：グローバル脳虚血のラットモデル

Cardiac arrest followed by resuscitation often results in dramatic brain damage caused by ischemia and subsequent reperfusion of the brain. Global brain ...

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment (RMCA) in Individuals with Chronic Spinal Cord Injury

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination is disrupted by spinal cord injury (SCI), control of respiratory muscles innervated below the injury level is compromised1,2 leading to respiratory muscle dysfunction and pulmonary complications. These conditions are among the leading causes of death in patients with SCI3. Standard pulmonary function tests that assess respiratory motor function include spirometrical and maximum airway pressure outcomes: Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), Maximal Inspiratory Pressure (PImax) and Maximal Expiratory Pressure (PEmax)4,5. These values provide indirect measurements of respiratory muscle performance6. In clinical practice and research, a surface electromyography (sEMG) recorded from respiratory muscles can be used to assess respiratory motor function and help to diagnose neuromuscular pathology. However, variability in the sEMG amplitude inhibits efforts to develop objective and direct measures of respiratory motor function6. Based on a multi-muscle sEMG approach to characterize motor control of limb muscles7, known as the voluntary response index (VRI)8, we developed an analytical tool to characterize respiratory motor control directly from sEMG data recorded from multiple respiratory muscles during the voluntary respiratory tasks. We have termed this the Respiratory Motor Control Assessment (RMCA)9. This vector analysis method quantifies the amount and distribution of activity across muscles and presents it in the form of an index that relates the degree to which sEMG output within a test-subject resembles that from a group of healthy (non-injured) controls. The resulting index value has been shown to have high face validity, sensitivity and specificity9-11. We showed previously9 that the RMCA outcomes significantly correlate with levels of SCI and pulmonary function measures. We are presenting here the method to quantitatively compare post-spinal cord injury respiratory multi-muscle activation patterns to those of healthy individuals.

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment RMCA in Individuals with Chronic Spinal Cord Injury

The purpose of this publication is to present our original work on a multi-muscle surface electromyographic approach to quantitatively characterize respiratory muscle activation patterns in individuals with chronic spinal cord injury using vector-based analysis.

慢性脊髄損傷患者で呼吸器モータ制御評価（RMCA）を使用して呼吸筋活動の評価

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination ...

Reproducable Paraplegia by Thoracic Aortic Occlusion in a Murine Model of Spinal Cord Ischemia-reperfusion

Background 
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury.&#160;The current model demonstrates reproducible lower&#160;extremity paralysis following thoracic aortic occlusion.
Methods 
Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery.&#160; Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr.
Results 
Mice that underwent sham surgery showed no observable hind&#160;limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post&#160;operative mortality.
Conclusion 
Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved.

The lack of mechanistic understanding of spinal cord ischemia-reperfusion injury has hindered further adjuncts to prevent paraplegia following high risk aortic operations. Thus, the development of animal models is imperative. This manuscript demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion in a murine model.

脊髄虚血再灌流のマウスモデルにおいて胸部大動脈閉塞によって再現可能対麻痺

Background
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered ...

Controlled Cortical Impact Model for Traumatic Brain Injury

Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.

Traumatic brain injuries (TBIs) remain a serious health problem. Using the controlled cortical impact surgery model, research on the effects of TBI and possible treatment methods may be performed.

外傷性脳損傷のための制御皮質衝撃モデル

Every year over a million Americans suffer a traumatic brain injury (TBI).  Combined with the incidence of TBIs worldwide, the physical, emotional, ...

A Radio-telemetric System to Monitor Cardiovascular Function in Rats with Spinal Cord Transection and Embryonic Neural Stem Cell Grafts

High thoracic or cervical spinal cord injury (SCI) can lead to cardiovascular dysfunction. To monitor cardiovascular parameters, we implanted a catheter connected to a radio transmitter into the femoral artery of rats that underwent a T4 spinal cord transection with or without grafting of embryonic brainstem-derived neural stem cells expressing green fluorescent protein. Compared to other methods such as cannula insertion or tail-cuff, telemetry is advantageous to continuously monitor blood pressure and heart rate in freely moving animals. It is also capable of long term multiple data acquisitions. In spinal cord injured rats, basal cardiovascular data under unrestrained condition and autonomic dysreflexia in response to colorectal distension were successfully recorded. In addition, cardiovascular parameters before and after SCI can be compared in the same rat if a transmitter is implanted before a spinal cord transection. One limitation of the described telemetry procedure is that implantation in the femoral artery may influence the blood supply to the ipsilateral hindlimb.

We present a protocol for using a radio-telemetric system to record cardiovascular parameters in T4 spinal cord transected rats eight weeks after embryonic brainstem neural stem cell grafting into the lesion site. Telemetry is an advanced technique to accurately evaluate cardiovascular function in conscious freely moving spinal cord injured rats.

ラジオ遠隔測定システムは、脊髄離断および胚性神経細胞移植片幹ラットの心臓血管機能を監視する

High thoracic or cervical spinal cord injury (SCI) can lead to cardiovascular dysfunction. To monitor cardiovascular parameters, we implanted a catheter ...

Photothrombosis-induced Focal Ischemia as a Model of Spinal Cord Injury in Mice

Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) below the site of injury. The secondary ischemia that develops following the initial mechanical insult is a serious complication of the SCI and severely impairs the function and viability of surviving neuronal and non-neuronal cells in the SC. In addition, ischemia is also responsible for the growth of lesion during chronic phase of injury and interferes with the cellular repair and healing processes. Thus there is a need to develop a spinal cord ischemia model for studying the mechanisms of ischemia-induced pathology. Focal ischemia induced by photothrombosis (PT) is a minimally invasive and very well established procedure used to investigate the pathology of ischemia-induced cell death in the brain. Here, we describe the use of PT to induce an ischemic lesion in the spinal cord of mice. Following retro-orbital sinus injection of Rose Bengal, the posterior spinal vein and other capillaries on the dorsal surface of SC were irradiated with a green light resulting in the formation of a thrombus and thus ischemia in the affected region. Results from histology and immunochemistry studies show that PT-induced ischemia caused spinal cord infarction, loss of neurons and reactive gliosis. Using this technique a highly reproducible and relatively easy model of SCI in mice can be achieved that would serve the purpose of scientific investigations into the mechanisms of ischemia induced cell death as well as the efficacy of neuroprotective drugs. This model will also allow exploration of the pathological changes that occur following SCI in live mice like axonal degeneration and regeneration, neuronal and astrocytic Ca2+ signaling using two-photon microscopy.

Photothrombosis is a minimally invasive and highly reproducible procedure to induce focal ischemia in the spinal cord and serves as a model of spinal cord injury in mice.

マウスの脊髄損傷のモデルとしての光血栓誘発性局所虚血

Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) ...

A Neonatal Mouse Spinal Cord Compression Injury Model

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life1, this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques1. Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections1.

This article describes a method for generating a reproducible spinal cord compression injury (SCI) in the neonatal mouse. The model provides an advantageous platform for studying mechanisms of adaptive plasticity that underlie spontaneous functional recovery.

新生児マウス脊髄圧縮損傷モデル

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal ...

Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model

Percutaneous vascular interventions uniformly result in arterial denudation injuries that subsequently lead to thrombosis and restenosis. These complications can be attributed to impairments in re-endothelialization within the wound margins. Yet, the cellular and molecular mechanisms of re-endothelialization remain to be defined. While several animal models to study re-endothelialization after arterial denudation are available, few are performed in the mouse because of surgical limitations. This undermines the opportunity to exploit transgenic mouse lines and investigate the contribution of specific genes to the process of re-endothelialization. Here, we present a step-by-step protocol for creating a highly reproducible murine model of arterial denudation injury in the infrarenal abdominal aorta using external vascular clamping. Immunocytochemical staining of injured aortas for fibrinogen and &#946;-catenin demonstrate the exposure of a pro-thrombotic surface and the border of intact endothelium, respectively. The method presented here has the advantages of speed, excellent overall survival rate, and relative technical ease, creating a uniquely practical tool for imposing arterial denudation injury in transgenic mouse models. Using this method, investigators may elucidate the mechanisms of re-endothelialization under normal or pathological conditions.

Understanding the cellular and molecular mechanisms of re-endothelialization following arterial denudation injury is of paramount importance in preventing thrombosis and restenosis of arteries. Here we describe a protocol for reproducible arterial denudation injury of the infrarenal abdominal aorta. The procedure was developed to investigate the underlying mechanisms that regulate endothelial regeneration using mouse models.