LTは、大学医学部ゲッティンゲンForschungsförderungsprogrammから助成金を受けています。 PLとMBは脳の分子生理学（CMPB）、ゲッティンゲンのためのDFG研究センターによってサポートされていました。著者らは、オーディオとビデオ編集のヘルプのためのビデオ撮影とビルギットLiebauの支援については博士ラースTatenhorstに感謝します。

動物は、ジャクソン研究所（＃002726）1から購入した。それらは臨床的に獲得し、運動機能（ロータロッド試験）と筋力（ワイヤ試験をぶら下げ）の試験に供されています。すべてのこれらの試験や動物の殺害後脊髄を準備するためには、動物実験の適正な実施のためのローカルガイドラインに非常に近くに基づき行われてきた。 1。臨床スコア別に体重マウスの評価から以下の4点のスコアリングシステム2運動障害の兆候がないか調べられます： 4点：通常（運動機能障害の兆し） 3点：尾によって中断されたときに後肢の震えは明白です 2点：歩行異常が存在 1点：少なくとも一つの後肢のドラッグ 0点：対称麻痺自体右側にできない、または最大体重の20％の損失が、この場合には動物は直ちに安楽死させ、実験が終了した 2。運動機能のテストと筋力ワイヤーハンギングこのテストは、筋力3、4を評価するために使用されています。すべての動物は、少なくとも1日か2日ロータロッドテストの後にこのテストを実行します。各マウスは0.8 cmの間隔でカスタムメイドの線の蓋の上に置き、慎重に逆さまになっている、藁上に60 cmの底部を覆った。少なくとも180秒の3回連続しての訓練の後に落ちるように遅延が測定されます。各マウスは、180秒の最大かつ最長の期間が記録されているため、反転蓋を保持するには、次の3つの試行までに与えられます。 ロータロッドテスト3、4を用いて測定した。優れた性能は感覚調整の高い学位を必要とします。マシンがテストされた動物の気を散らす刺激を避けるために、穏やかな、非妨害環境に配置する必要があります。それはコンピュータ制御のモーター駆動回転スピンドルと5匹のマウスのための5つのレーンで構成されています。マウスの滝は下部のプラスチック板に圧力を自動的に検出されます。 15 rpmの一定速度で少なくとも180秒の3回連続しての訓練後、動物は回転棒上に残ることができるの時間が測定されます。各動物は、3つの試験と立ち下がりが記録されずに長い待ち時間を受ける。運動協調性に有意差の大半がこの時間枠内で検出されているため、180秒の時間がカットオフ時間として選択されます。 3。脊髄の準備<ol class="lalpha"><li>動物は、地元のガイドラインに従い、CO 2吸入によって殺されており、すぐに4％パラホルムアルデヒド溶液、続いてPBS溶液でtranscardially灌流されています。 </li><li>犠牲にマウスの脊髄を準備するために、動物は、操作テーブルの上に配置され、四肢は、マウスの裏面を露出させるために側に固定されています。 </li><li> 70％エタノール溶液で短い洗浄は、解剖部位をきれいにし、髪のコートを平坦化します。 </li><li>その後、皮膚は正中線に鋭いメスで切開されています。皮膚を切る容易にするために両側に延伸される。脚の筋肉が準備されなければならない場合は、その皮膚が切開されることもあります。 </li><li>皮膚切開が完了したら、それはボディの基本的な表在筋膜を露出させるピンセットで脇にプルアップされています。 </li><li>首の筋肉と項靱帯を除去しなければならないとCAです。refully用意しました。深く病変脊髄に切開しないように注意してください。肩の筋肉にも優れた脊柱を露出させるために削除することができます。 </li><li>その後、傍脊柱筋全体脊柱から削除されます。 </li><li>脊柱を開くためには、いくつかのlaminectomiesは、実行する必要があります。一つは、環椎後頭関節のサイトで上位脳神経の部分から開始する必要があります。 </li><li>上部の2肢の固定を削除し、最初の脊椎の椎弓切除を行うことが良いことができるように首を引き伸ばし過ぎるのが最も簡単です。これらが露出し脊髄に触れずに引き離されています。 </li><li>多くの脊椎は、最初の角度をハサミで両側に脊椎のアーチをtransectingし、背側のプロセスに引いて削除されます。椎骨の残りの側面部分は脊髄の後の完全な除去を容易にするために削除する必要があります。 </li><li>腰部脊椎の解剖学的ランドマークlのコードはまた、頚部脊髄に存在して腫れることがあります。 </li><li>全体脊髄の椎弓切除を終え、あなたもすべての腹根を横断すると髄膜の硬膜から脊髄を解放することを確認してください。 </li><li>その後、脊髄は頭側カットとは、脊髄を除去するために開始されています。 </li><li>最後に、脊髄も完全に解放される遠位馬尾·馬尾で切断されています。 </li><li>最終的に、脊髄を一晩postfixating溶液（例えば4％パラホルムアルデヒド）に配置され、さらに処理することができます。我々は通常、免疫組織学的解析のためにそれを準備する脊髄凍結切片。 </li></ol> 4。代表的な結果脊髄の準備のテクニックは、このビデオの記事の焦点を表しています。これは後に組織切片のために、最終的には脊椎の免疫組織学的解析のために必須の前提条件です。lのコードのセクションを参照してください。最終結果の一例として、野生型マウスの腰部脊髄（WT）およびSOD G93Aトランス（TG）マウスの前角領域の免疫組織化学的後処理が実証されています。運動ニューロンは、一次抗ChATの抗体および二次Cy3標識抗体を用いて、後続の蛍光標識を識別することができます。さらに、DAPI（4,6 -ジアミジノ-2 -フェニル）核カウンター染色（ 図1）が実行されています。 <img src="/files/ftp_upload/3936/3936fig1.jpg" alt="図1" /> 図1抗ChATの抗体（赤）と野生型（WT）マウスの腰部脊髄前角（左側）とのDAPI（青）による細胞核のカウンター染色と運動ニューロンの免疫を可視化する蛍光顕微鏡SOD G93Aトランスジェニック（Tg）（右）130日齢のマウス。スケールバー：40μm以下。 の免疫組織化学的分析などSOD G93Aマウスは、この記事のプライマリスコープではありませんこれらのトランスジェニックマウスが特徴づけられているた元の出版物、さらに、参照1、5、6のために治療法を勉強し、より最近のものを参照してください。治療効果が明確に定義された免疫組織学的レベルで区別されなければならない場合、定量的な評価アルゴリズムは、立体的なソフトウェア（例えば、7を参照）でサポートされて適用されるべきである。

<ol>
	<li>Gurney, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+neuron+degeneration+in+mice+that+express+a+human+Cu,+Zn+superoxide+dismutase+mutation.">Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation.</a> Science. 264 (5166), 1772-1775 (1994).</li><li>Weydt, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessing+disease+onset+and+progression+in+the+SOD1+mouse+model+of+ALS.">Assessing disease onset and progression in the SOD1 mouse model of ALS.</a> Neuroreport. 14 (7), 1051-1054 (2003).</li><li>Crawley, J. 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L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuromuscular+disease+models+and+analysis.">Neuromuscular disease models and analysis.</a> Methods Mol. Biol. 602, 347-393 (2010).</li><li>Hayworth, C. R., Gonzalez-Lima, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pre-symptomatic+detection+of+chronic+motor+deficits+and+genotype+prediction+in+congenic+B6.SOD1(G93A)+ALS+mouse+model.">Pre-symptomatic detection of chronic motor deficits and genotype prediction in congenic B6.SOD1(G93A) ALS mouse model.</a> Neuroscience. 164 (3), 975-985 (2009).</li><li>Ludolph, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+preclinical+animal+research+in+ALS&#47;MND:+A+consensus+meeting.">Guidelines for preclinical animal research in ALS&#47;MND: A consensus meeting.</a> Amyotroph Lateral Scler. 11 (1-2), 38-45 (2010).</li><li>Boillee, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Onset+and+progression+in+inherited+ALS+determined+by+motor+neurons+and+microglia.">Onset and progression in inherited ALS determined by motor neurons and microglia.</a> Science. 5778 (3), 1389-1392 (2006).</li></ol>

利害の衝突が宣言されません。

SOD1（G93A）の遺伝的マウスモデルはヒトの筋萎縮性側索硬化症8に匹敵する進歩的な運動ニューロン損失の疾患経過を研究する貴重な動物モデルである。異なる治療パラダイムの様々なこのモデルでは評価され、後で人間の臨床試験8-10にテストするための基礎を表すされています。これらのマウスの実験的治療の研究では有意差を検出することができるようにするためには、?...

<table border="1"><tbody><tr><td></td><td> メーカー </td><td> オーダ情報 </td></tr><tr><td> 行動実験 </td><td></td><td></td></tr><tr><td>マウス用ロータロッド</td><td>ウーゴ·バジーレ、Comerio、イタリア</td><td> ＃47600 </td></tr><tr><td> Wireデバイスをぶら下げ</td><td>カスタムメード</td><td></td></tr><tr><td colspan="3"></td></tr><tr><td> 脊髄の準備 </td><td></td><td></td></tr><tr><td>演算表 動作ランプ 保護手袋</td><td></td><td></td></tr><tr><td>側に角度 &quot;アイリス&quot;はさみ、 </td><td>ファイン科学ツール、ハイデルベルク、ドイツ</td><td> 14063から09 </td></tr><tr><td>コー​​ハン-Vannas春のはさみ、ストレート</td><td>ファイン科学ツール、ハイデルベルク、ドイツ</td><td> 15000から10 </td&gt; </tr><tr><td>マイクロ鉗子</td><td> Hammacher、ゾーリンゲン、ドイツ</td><td> HWC 111から10 </td></tr><tr><td>メス &quot;präzisaプラス&quot; </td><td> Dahlhausen、ケルン、ドイツ</td><td> 11.000.00.510、図10 </td></tr></tbody></table>

clinical testing and spinal cord removal in a mouse model for amyotrophic lateral sclerosis (als)

筋萎縮性側索硬化症（ALS）は運動ニューロンの進行性変性をもたらす致命的な神経変性疾患である。発症のピークは散発的な疾患および家族性疾患のため50歳前後60歳前後である。その進行性の経過により、患者の50％は、発症から30ヶ月以内に死亡する。この病気のための新たな治療の選択肢を評価するために、ALSの遺伝子のマウスモデルは、そのようなSOD1（G93A）突然変異としてSOD遺伝子の人間の家族の変異に基づいて生成されています。モデルで評価しなければならない最も重要な側面は、全生存期間、臨床経過と運動機能があります。ここでは、臨床評価を示し、二つの行動モーターテストの伝導を示し、すべてのパラメータの定量的なスコアリングシステムを提供しています。 ALSモデルマウスの深さ分析の通常脊髄の免疫組織化学的検査を必要とするため、我々は何を適用する詳細にその準備を実証rsal椎弓切除術の方法。典型的な組織学的所見が実証されています。 ALSのモデルマウスの研究で示され検査法の包括的なアプリケーションは、研究者が確実に後でヒト臨床試験のための基礎を提供することができ、将来の治療オプションをテストすることが可能になります。

Watch this Scientific Journal Video about Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis ALS at JoVE.com

Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis ALS

筋萎縮性側索硬化症（ALS）のマウスモデルは、臨床的および行動的に検討されている。付随する免疫組織学的分析のための前提条件として、脊髄の調製は、詳細に描かれています。

臨床試験および筋萎縮性側索硬化症（ALS）のマウスモデルにおける脊髄の除去

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in progressive degeneration of motoneurons. Peak of onset is around 60 ...

clinical-testing-spinal-cord-removal-mouse-model-for-amyotrophic

Research

JoVE Journal

Medicine

Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis (ALS)

27.9K ビュー.  University Medicine Göttingen. 筋萎縮性側索硬化症（ALS）のマウスモデルは、臨床的および行動的に検討されている。付随する免疫組織学的分析のための前提条件として、脊髄の調製は、詳細に描かれています。

ビデオ: Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis ALS

A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis (ALS)

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression across speech subsystems, and for addressing the critical need for sensitive outcome measures for ongoing experimental treatment trials. To address this need, we are obtaining longitudinal profiles of bulbar impairment in 100 individuals based on a comprehensive instrumentation-based assessment that yield objective measures. Using instrumental approaches to quantify speech-related behaviors is very important in a field that has primarily relied on subjective, auditory-perceptual forms of speech assessment1. Our assessment protocol measures performance across all of the speech subsystems, which include respiratory, phonatory (laryngeal), resonatory (velopharyngeal), and articulatory. The articulatory subsystem is divided into the facial components (jaw and lip), and the tongue. Prior research has suggested that each speech subsystem responds differently to neurological diseases such as ALS. The current protocol is designed to test the performance of each speech subsystem as independently from other subsystems as possible. The speech subsystems are evaluated in the context of more global changes to speech performance. These speech system level variables include speaking rate and intelligibility of speech.
The protocol requires specialized instrumentation, and commercial and custom software. The respiratory, phonatory, and resonatory subsystems are evaluated using pressure-flow (aerodynamic) and acoustic methods. The articulatory subsystem is assessed using 3D motion tracking techniques. The objective measures that are used to quantify bulbar impairment have been well established in the speech literature and show sensitivity to changes in bulbar function with disease progression. The result of the assessment is a comprehensive, across-subsystem performance profile for each participant. The profile, when compared to the same measures obtained from healthy controls, is used for diagnostic purposes. Currently, we are testing the sensitivity and specificity of these measures for diagnosis of ALS and for predicting the rate of disease progression. In the long term, the more refined endophenotype of bulbar ALS derived from this work is expected to strengthen future efforts to identify the genetic loci of ALS and improve diagnostic and treatment specificity of the disease as a whole. The objective assessment that is demonstrated in this video may be used to assess a broad range of speech motor impairments, including those related to stroke, traumatic brain injury, multiple sclerosis, and Parkinson disease.

A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis ALS

Objective assessments of the physiological mechanisms that support speech are needed to monitor disease onset and progression in persons with ALS and to quantify treatment effects in clinical trials. In this video, we present a comprehensive, instrumentation-based protocol for quantifying speech motor performance in clinical populations.

筋萎縮性側索硬化症における延髄機能障害の包括的評価（ALS）のためのプロトコル

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression ...

医学

Intraspinal Cell Transplantation for Targeting Cervical Ventral Horn in Amyotrophic Lateral Sclerosis and Traumatic Spinal Cord Injury

Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) cases 1 and is the ultimate cause of death in patients with the motor neuron disorder, amyotrophic laterals sclerosis (ALS) 2.
ALS is a devastating neurological disorder that is characterized by relatively rapid degeneration of upper and lower motor neurons. Patients ultimately succumb to the disease on average 2-5 years following diagnosis because of respiratory paralysis due to loss of phrenic motor neuron innnervation of the diaphragm 3. The vast majority of cases are sporadic, while 10% are of the familial form. Approximately twenty percent of familial cases are linked to various point mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene on chromosome 21 4. Transgenic mice 4,5 and rats 6 carrying mutant human SOD1 genes (G93A, G37R, G86R, G85R) have been generated, and, despite the existence of other animal models of motor neuron loss, are currently the most highly used models of the disease.
Spinal cord injury (SCI) is a heterogeneous set of conditions resulting from physical trauma to the spinal cord, with functional outcome varying according to the type, location and severity of the injury 7. Nevertheless, approximately half of human SCI cases affect cervical regions, resulting in debilitating respiratory dysfunction due to phrenic motor neuron loss and injury to descending bulbospinal respiratory axons 1. A number of animal models of SCI have been developed, with the most commonly used and clinically-relevant being the contusion 8.
Transplantation of various classes of neural precursor cells (NPCs) is a promising therapeutic strategy for treatment of traumatic CNS injuries and neurodegeneration, including ALS and SCI, because of the ability to replace lost or dysfunctional CNS cell types, provide neuroprotection, and deliver gene factors of interest 9.
Animal models of both ALS and SCI can model many clinically-relevant aspects of these diseases, including phrenic motor neuron loss and consequent respiratory compromise 10,11. In order to evaluate the efficacy of NPC-based strategies on respiratory function in these animal models of ALS and SCI, cellular interventions must be specifically directed to regions containing therapeutically relevant targets such as phrenic motor neurons. We provide a detailed protocol for multi-segmental, intraspinal transplantation of NPCs into the cervical spinal cord ventral gray matter of neurodegenerative models such as SOD1G93A mice and rats, as well as spinal cord injured rats and mice 11.

Neural precursor transplantation is a promising strategy for protecting and/or replacing lost/dysfunctional cervical phrenic motor neurons in spinal cord injury (SCI) and the motor neuron disorder, amyotrophic laterals sclerosis (ALS). We provide a protocol for cell delivery to cervical spinal cord ventral horn in rodent models of ALS and SCI.

筋萎縮性側索硬化症や外傷性脊髄損傷では頚椎前角をターゲットとするための髄腔内細胞移植

Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) ...

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 ...

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 ...

Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis

The split hand phenomenon refers to predominant wasting of thenar muscles and is an early and specific feature of amyotrophic lateral sclerosis (ALS). A novel split hand index (SI) was developed to quantify the split hand phenomenon, and its diagnostic utility was assessed in ALS patients. The split hand index was derived by dividing the product of the compound muscle action potential (CMAP) amplitude recorded over the abductor pollicis brevis and first dorsal interosseous muscles by the CMAP amplitude recorded over the abductor digiti minimi muscle. In order to assess the diagnostic utility of the split hand index, ALS patients were prospectively assessed and their results were compared to neuromuscular disorder patients. The split hand index was significantly reduced in ALS when compared to neuromuscular disorder patients (P&#60;0.0001). Limb-onset ALS patients exhibited the greatest reduction in the split&#160;hand index, and a value of 5.2 or less reliably differentiated ALS from other neuromuscular disorders. Consequently, the split&#160;hand index appears to be a novel diagnostic biomarker for ALS, perhaps facilitating an earlier diagnosis.

Dissociated atrophy of intrinsic hand muscles, termed the split hand, appears to be a specific feature of amyotrophic lateral sclerosis (ALS).&#160;Consequently, a novel neurodiagnostic test, termed the split hand&#160;index, was developed to quantify the clinical phenomenon of the split hand, which differentiated ALS from mimic disorders.

筋萎縮性側索硬化症の診断で解離極限ハンド筋萎縮の有用性

The split hand phenomenon refers to predominant wasting of thenar muscles and is an early and specific feature of amyotrophic lateral sclerosis (ALS). A ...

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 ...

Calibrated Forceps Model of Spinal Cord Compression Injury

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The calibrated forceps model of compression injury is a convenient, low cost, and very reproducible animal model for SCI. We used a pair of modified forceps in accordance with the method published by Plemel et al. (2008) to laterally compress the spinal cord to a distance of 0.35 mm. In this video, we will demonstrate a dorsal laminectomy to expose the spinal cord, followed by compression of the spinal cord with the modified forceps. In the video, we will also address issues related to the care of paraplegic laboratory animals. This injury model produces mice that exhibit impairment in sensation, as well as impaired hindlimb locomotor function. Furthermore, this method of injury produces consistent aberrations in the pathology of the SCI, as determined by immunohistochemical methods. After watching this video, viewers should be able to determine the necessary supplies and methods for producing SCI of various severities in the mouse for studies on SCI and/or treatments designed to mitigate impairment after injury.

Spinal cord injury models should be highly reproducible. We demonstrate that the calibrated forceps compression model of spinal cord injury is an easy to use surgical method for generating reproducible injuries to the murine spinal cord.

脊髄圧縮傷害の校正済み鉗子モデル

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The ...

A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening protocol, demonstrated in video herein, which reliably assesses the neuromuscular function of SOD1-G93A mice in a quick manner. This protocol encompasses a simple neurological scoring system (NeuroScore) designed to assess hindlimb function. NeuroScore is focused on hindlimb function because hindlimb deficits are the earliest reported neurological sign of disease in SOD1-G93A mice. The protocol developed by ALS TDI provides an unbiased assessment of onset of paresis (slight or partial paralysis), progression and severity of paralysis and it is sensitive enough to identify drug-induced changes in disease progression. In this report, the combination of a detailed manuscript with video minimizes scoring ambiguities and inter-experimenter variability thus allowing for the protocol to be adopted by other laboratories and enabling comparisons between studies taking place at different settings. We believe that this video protocol can serve as an excellent training tool for present and future ALS researchers.

This video protocol describes a sensitive, reliable, and quick method for evaluating the neuromuscular deficits in a transgenic mouse model of amyotrophic lateral sclerosis.

ALSのSOD1-G93Aマウスモデルにおける疾患進行を評価するためのクイック表現型の神経学的スコアリングシステム

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening ...

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 ...