この作品は、フランスの公共投資委員会によって割り当てられたグラント契約番号246556（欧州プロジェクトRBUCE-UP）、HandiMedExの下で、欧州連合（EU）セブンス·フレームワーク·プログラム（FP7/2007-2013）からの資金によってサポートされています。マルセルBonayはサンテRespiratoire、およびセンター - 援助Respiratoireà法人住所D&#39;イル=ド=フランス（CARDIF）JPフォン·ド·寄託金ルシェルシュ、Chancellerie DESUniversités·ド·パリ（脚POIX）によってサポートされていました

このプロトコルは、優秀（パリシュッド、グラント契約番号246556の大学）と大学·ド·ベルサイユサンカンタン·アン·イヴリーヌのRBUCEアップ椅子の倫理委員会によって承認された。 滅菌手術器具の1。準備<ol><li>実験室の洗剤で手術器具を清掃してください。 </li><li>手術前に楽器をオートクレーブ。 </li><li>外科セッションでは、2の手術の間、180℃で10分間ホットビーズ滅菌器でのヒントを配置することでツールを殺菌。 </li></ol>医薬品の2。準備<ol><li>前麻酔薬カクテルや術後の薬のために2×1ミリリットル注射器を準備します。 </li><li>カルプロフェン（5 mg / kg）を、ブプレノルフィン（50μgの/ kg）を、バイトリル（5 mg / kg）をし、デクスメデトミジン（0.5 mg / kg）をラットの体重に応じて、事前に麻酔薬を注射器を準備します。乳酸リンゲル液に1ミリリットルにボリュームを完了します。 </li><li>中準備別のシリンジプレ麻酔薬の逆転：アチパメゾール（500μgの/キロ）。 </li></ol>ラットの3。麻酔<ol><li>動物にステップ2.2で説明した前の麻酔薬の溶液を皮下投与する。その後、戻ってケージに動物を入れて、鎮静効果が表示されるまで待ちます。 </li><li> 100％のO 2、5％イソフルランでいっぱいにクローズ室にラットを置き、呼吸リズムが（30秒程度）遅くなるまで待ちます。その後、チャンバーからラットを削除し、挿管のテーブルの上に置きます。 </li></ol> 4。経口気管内挿管<ol><li>テーブルに彼の前歯に付属のストラップを配置することにより、ヘッドを固定した後、彼の背中に動物に存在する。 </li><li>光ファイバの光で、胸部のスペースを照らす。その後、動物の口の中に喉頭鏡（または1をカスタムメイド、詳細は城之内ら 20）を配置します。声帯を視覚化する。 </li><li> SLIDEと（声帯の間）気管内に経口気管ガイドを配置。ガイドに経口気管内チューブ（16gのカテーテルサイズ）をスライドさせます。 </li><li>ガイドを削除して、水分の存在のために経口気管内チューブの端部に配置され、喉頭鏡で確認し、気管内ではなく食道にチューブの適切な位置を確認した。 </li><li> （683齧歯類人工呼吸器、ハーバード装置）げっ歯類の人工呼吸器にチューブを接続し、（100％のO 2）で2％イソフルランの濃度を調整します。 </li><li>サージカルテープで経口気管内チューブを固定します。 </li></ol> 5。脊椎手術<ol><li>外科医に90°の角度を指して鼻で、加熱された手術用プレート上腹臥位の位置に動物を配置します。手術全体で37.5℃付近体温を維持。 </li><li>肩甲骨の間にバリカンで毛を剃るとガーゼで髪を削除します。 </li><li>それから7で、ベタジンで肌をきれいに0％アルコール。このステップ3回繰り返します。 </li><li>つま先のピンチは、適切な麻酔深度を確保するために、手術の開始前に行われる。 &#160;すると、肩甲骨の間にはさみで横方向の皮膚切開の吻側尾側を実行します。 </li><li>出血を防ぐために、腱に従うことによってacromiotrapezius筋吻側尾側をカットします。その後、脊髄筋（脊椎骨の周囲）にアクセスするための菱形筋を解離する。 </li><li> C3は椎骨にC1から脊髄の筋肉を撤回。 C2は椎骨は、著名な骨端を有するものである。 </li><li>無菌綿棒を使って、椎骨の背側部分の周りの筋肉を清掃してください。 </li><li>骨鉗子で慎重にC2の骨端を除去して起動します。背側脊髄が露出するまで、細心の注意を払って継続する。椎弓切除術は、背側半椎弓切除術であることを確認してください。脊髄を囲む硬膜、この領域の近傍の動脈に細心の注意を払う。 </li><li> ＃55ピンセットで、ROSを解剖TRO-尾C2方向硬膜は、次の各吻側および尾側に横方向に続けています。 </li><li>脳脊髄液をスポンジ。 </li><li> microscissorsと頸椎後根番号2の下の横方向のセクションを作る。病変の程度は（傷害の背側については、図2（a）参照 ）、脊髄の正中線に到達するのに十分近いことをマイクロメスで確認してください。そうでない場合には、別のカットが損傷を完了するために行うことができる。出血の場合には、滅菌した綿棒を使用しています。それ以外の場合は、動物が怪我から回復せず、呼吸不全を持って、反対側に行かないように注意してください。 </li><li>保護層としての筋肉を縫合し、皮膚を縫合バック。ベタジン飽和滅菌ガーゼで傷口をきれいにします。 </li><li>イソフルラン気化器をオフにして、反転薬（アチパメゾール[500μgの/ kgで、IM]）を注入し、体温をチェックしてください。 </li><li>動物は、人工呼吸器に対して息をし始めると、人工呼吸器から気管チューブを切断した後、経口気管内チューブを取り外します。回復のために加熱されたケージに動物を配置します。 </li></ol> 6。手術後のケア手術後、動物を回復するために可能な限り最高の環境を確保するために継続的に監視される。抗生物質（バイトリル、5 mg / kg）を、抗炎症（カルプロフェン、5ミリグラム/ kg）およびブプレノルフィン（50μgの/ kg）の薬物が感染を防止し、発生を低減する最初の2日間、12時間ごとに、手術後に与えられている手術後の痛みの。ラットは、（第一術後一日またはゼリー状水）ソフト食料と水へのアクセスを自由に摂取しています。皮下流体は、最初のいくつかの術後の日に脱水を予防するために用いることができる。体重および食物摂取量を毎日モニターする。その環境は、実験と時間、損傷後（デュアル住宅、ケージ内チューブ）を通じて濃縮されている。

<ol>
	<li>Frankel, H. 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=Long-term+survival+in+spinal+cord+injury:+a+fifty+year+investigation.">Long-term survival in spinal cord injury: a fifty year investigation.</a> Spinal Cord. 36, 266-274 (1998).</li><li>Ramer, M. S., Harper, G. P., Bradbury, E. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Progress+in+spinal+cord+research+-+a+refined+strategy+for+the+International+Spinal+Research+Trust.">Progress in spinal cord research - a refined strategy for the International Spinal Research Trust.</a> Spinal Cord. 38, 449-472 (2000).</li><li>Zimmer, M. B., Nantwi, K., Goshgarian, H. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+spinal+cord+injury+on+the+respiratory+system:+basic+research+and+current+clinical+treatment+options.">Effect of spinal cord injury on the respiratory system: basic research and current clinical treatment options.</a> J Spinal Cord Med. 30, 319-330 (2007).</li><li>Mantilla, C. B., Sieck, G. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuromuscular+adaptations+to+respiratory+muscle+inactivity.">Neuromuscular adaptations to respiratory muscle inactivity.</a> Respir Physiol Neurobiol. 169, 133-140 (2009).</li><li>Goshgarian, H. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+crossed+phrenic+phenomenon+and+recovery+of+function+following+spinal+cord+injury.">The crossed phrenic phenomenon and recovery of function following spinal cord injury.</a> Respir Physiol Neurobiol. 169, 85-93 (2009).</li><li>Nantwi, K. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recovery+of+respiratory+activity+after+C2+hemisection+(C2HS):+involvement+of+adenosinergic+mechanisms.">Recovery of respiratory activity after C2 hemisection (C2HS): involvement of adenosinergic mechanisms.</a> Respir Physiol Neurobiol. 169, 102-114 (2009).</li><li>Sandhu, M. S., 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=Respiratory+recovery+following+high+cervical+hemisection.">Respiratory recovery following high cervical hemisection.</a> Respir Physiol Neurobiol. 169, 94-101 (2009).</li><li>Lane, M. A., Lee, K. Z., Fuller, D. D., Reier, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spinal+circuitry+and+respiratory+recovery+following+spinal+cord+injury.">Spinal circuitry and respiratory recovery following spinal cord injury.</a> Respir Physiol Neurobiol. 169, 123-132 (2009).</li><li>Seeds, N. W., Akison, L., Minor, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+plasminogen+activator+in+spinal+cord+remodeling+after+spinal+cord+injury.">Role of plasminogen activator in spinal cord remodeling after spinal cord injury.</a> Respir Physiol Neurobiol. 169, 141-149 (2009).</li><li>Alilain, W. J., Horn, K. P., Hu, H., Dick, T. E., Silver, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+regeneration+of+respiratory+pathways+after+spinal+cord+injury.">Functional regeneration of respiratory pathways after spinal cord injury.</a> Nature. 475, 196-200 (2011).</li><li>Vinit, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cervical+spinal+cord+injuries+and+respiratory+insufficiency:+a+revolutionary+treatment.">Cervical spinal cord injuries and respiratory insufficiency: a revolutionary treatment.</a> Med Sci (Paris. 28, 33-36 (2012).</li><li>Kastner, A., Gauthier, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Are+rodents+an+appropriate+pre-clinical+model+for+treating+spinal+cord+injury?+Examples+from+the+respiratory+system).">Are rodents an appropriate pre-clinical model for treating spinal cord injury? Examples from the respiratory system).</a> Exp Neurol. 213, 249-256 (2008).</li><li>Vinit, S., Lovett-Barr, M. R., Mitchell, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intermittent+hypoxia+induces+functional+recovery+following+cervical+spinal+injury.">Intermittent hypoxia induces functional recovery following cervical spinal injury.</a> Physiol Neurobiol. 169, 210-217 (2009).</li><li>Porter, W. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Path+of+the+Respiratory+Impulse+from+the+Bulb+to+the+Phrenic+Nuclei.">The Path of the Respiratory Impulse from the Bulb to the Phrenic Nuclei.</a> J Physiol. 17, 455-485 .</li><li>Nicaise, C., 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=Phrenic+motor+neuron+degeneration+compromises+phrenic+axonal+circuitry+and+diaphragm+activity+in+a+unilateral+cervical+contusion+model+of+spinal+cord+injury.">Phrenic motor neuron degeneration compromises phrenic axonal circuitry and diaphragm activity in a unilateral cervical contusion model of spinal cord injury.</a> Exp Neurol. 235, 539-552 (2012).</li><li>Goshgarian, H. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+crossed+phrenic+phenomenon:+a+model+for+plasticity+in+the+respiratory+pathways+following+spinal+cord+injury.">The crossed phrenic phenomenon: a model for plasticity in the respiratory pathways following spinal cord injury.</a> J Appl Physiol. 94, 795-810 (2003).</li><li>Vinit, S., Gauthier, P., Stamegna, J. C., Kastner, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High+cervical+lateral+spinal+cord+injury+results+in+long-term+ipsilateral+hemidiaphragm+paralysis.">High cervical lateral spinal cord injury results in long-term ipsilateral hemidiaphragm paralysis.</a> J Neurotrauma. 23, 1137-1146 (2006).</li><li>Fuller, D. D., Johnson, S. M., Johnson, R. A., Mitchell, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+cervical+spinal+sensory+denervation+reveals+ineffective+spinal+pathways+to+phrenic+motoneurons+in+the+rat.">Chronic cervical spinal sensory denervation reveals ineffective spinal pathways to phrenic motoneurons in the rat.</a> Neurosci Lett. 323, 25-28 (2002).</li><li>Dougherty, B. J., Lee, K. Z., Lane, M. A., Reier, P. J., Fuller, D. D. <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+the+spontaneous+crossed-phrenic+phenomenon+to+inspiratory+tidal+volume+in+spontaneously+breathing+rats.">Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats.</a> J Appl Physiol. 112, 96-105 (2012).</li><li>Jou, I. M., 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=Simplified+rat+intubation+using+a+new+oropharyngeal+intubation+wedge.">Simplified rat intubation using a new oropharyngeal intubation wedge.</a> J Appl Physiol. 89, 1766-1770 (2000).</li><li>Fuller, D. D., 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=Graded+unilateral+cervical+spinal+cord+injury+and+respiratory+motor+recovery.">Graded unilateral cervical spinal cord injury and respiratory motor recovery.</a> Respir Physiol Neurobiol. 165, 245-253 (2009).</li><li>Vinit, S., Windelborn, J. A., Mitchell, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lipopolysaccharide+attenuates+phrenic+long-term+facilitation+following+acute+intermittent+hypoxia.">Lipopolysaccharide attenuates phrenic long-term facilitation following acute intermittent hypoxia.</a> Respir Physiol Neurobiol. 176, 130-135 (2011).</li><li>Ahmad, F., Wang, M. Y., Levi, A. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hypothermia+for+Acute+Spinal+Cord+Injury-A+Review.">Hypothermia for Acute Spinal Cord Injury-A Review.</a> World Neurosurg. , (2013).</li><li>Lovett-Barr, M. R., 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=Repetitive+intermittent+hypoxia+induces+respiratory+and+somatic+motor+recovery+after+chronic+cervical+spinal+injury.">Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury.</a> J Neurosci. 32, 3591-3600 (2012).</li><li>Minor, K. H., Akison, L. K., Goshgarian, H. G., Seeds, N. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spinal+cord+injury-induced+plasticity+in+the+mouse--the+crossed+phrenic+phenomenon.">Spinal cord injury-induced plasticity in the mouse--the crossed phrenic phenomenon.</a> Exp Neurol. 200, 486-495 (2006).</li><li>Baussart, B., Stamegna, J. C., Polentes, J., Tadie, M., Gauthier, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+model+of+upper+cervical+spinal+contusion+inducing+a+persistent+unilateral+diaphragmatic+deficit+in+the+adult+rat.">A new model of upper cervical spinal contusion inducing a persistent unilateral diaphragmatic deficit in the adult rat.</a> Neurobiol Dis. 22, 562-574 (2006).</li><li>Golder, F. 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=Breathing+patterns+after+mid-cervical+spinal+contusion+in+rats.">Breathing patterns after mid-cervical spinal contusion in rats.</a> Exp Neurol. 231, 97-103 (2011).</li><li>Lane, M. 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=Respiratory+function+following+bilateral+mid-cervical+contusion+injury+in+the+adult+rat.">Respiratory function following bilateral mid-cervical contusion injury in the adult rat.</a> Exp Neurol. 235, 197-210 (2012).</li><li>Vinit, S., 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=Axotomized+bulbospinal+neurons+express+c-Jun+after+cervical+spinal+cord+injury.">Axotomized bulbospinal neurons express c-Jun after cervical spinal cord injury.</a> Neuroreport. 16, 1535-1539 (2005).</li><li>Guenther, C. H., Windelborn, J. A., Tubon, T. C., Yin, J. C., Mitchell, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+atypical+PKC+expression+and+activity+in+the+phrenic+motor+nucleus+following+cervical+spinal+injury.">Increased atypical PKC expression and activity in the phrenic motor nucleus following cervical spinal injury.</a> Exp Neurol. 234, 513-520 (2012).</li><li>Mantilla, C. B., Gransee, H. M., Zhan, W. Z., Sieck, G. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motoneuron+BDNF/TrkB+signaling+enhances+functional+recovery+after+cervical+spinal+cord+injury.">Motoneuron BDNF/TrkB signaling enhances functional recovery after cervical spinal cord injury.</a> Exp Neurol. 247, 101-109 (2013).</li><li>Vinit, S., Darlot, F., Aoulaiche, H., Boulenguez, P., Kastner, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinct+expression+of+c-Jun+and+HSP27+in+axotomized+and+spared+bulbospinal+neurons+after+cervical+spinal+cord+injury.">Distinct expression of c-Jun and HSP27 in axotomized and spared bulbospinal neurons after cervical spinal cord injury.</a> J Mol Neurosci. 45, 119-133 (2011).</li><li>Windelborn, J. A., Mitchell, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glial+activation+in+the+spinal+ventral+horn+caudal+to+cervical+injury.">Glial activation in the spinal ventral horn caudal to cervical injury.</a> Respir Physiol Neurobiol. 180, 61-68 (2012).</li><li>Vinit, S., Stamegna, J. C., Boulenguez, P., Gauthier, P., Kastner, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Restorative+respiratory+pathways+after+partial+cervical+spinal+cord+injury:+role+of+ipsilateral+phrenic+afferents.">Restorative respiratory pathways after partial cervical spinal cord injury: role of ipsilateral phrenic afferents.</a> Eur J Neurosci. 25, 3551-3560 (2007).</li><li>Dougherty, B. 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=Recovery+of+inspiratory+intercostal+muscle+activity+following+high+cervical+hemisection.">Recovery of inspiratory intercostal muscle activity following high cervical hemisection.</a> Respir Physiol Neurobiol. 183, 186-192 (2012).</li></ol>

著者は、彼らが競合する経済的利益を持っていないことを宣言します。

C2は傷害モデルを作る技術的な問題 C2の損傷のマウスモデルでは、呼吸器、ポスト病変神経可塑性を研究するための興味深いツールです。しかし、再現性と信頼性の高いモデルを作成するために必要な手順が多数あり、それぞれが研究の結果に影響を与える可能性がある。たとえば、挿管過程で細心の注意を経口気管内チューブが怪我自体に起因する初期の...

脊髄損傷は、永久的な麻痺などの劇的な発生率とのヒト集団において観察された一般的な傷害である。しかし、損傷の重症度は、最初の外傷の程度と範囲に依存します。呼吸不全は、上部頸椎脊髄損傷（SCI）1以下の死亡率の主な原因である。現在、唯一の治療的処置は、換気補助の下に患者を配置することです。少数の患者は、後の病変の遅延で発生する自然回復による換気支援2をオフに離乳することができるので、新しい革新的な非侵襲的な治療薬を開発する必要性が緊急3である。 、推定治療戦略の適用を研究し、そのため呼吸不全に対する子宮頸SCIの効果を調査してもいい標準化された前臨床モデルを持つことは不可欠です。 この技術的な記事では、特定の前臨床マウスモデルOを記述C2レベルでの部分的な子宮頸SCIによって誘導されたF呼吸障害。このモデルは、現在、（：4月13日のレビューのために）、世界中のいくつかの研究室で使用されます。しかし、外科的処置のわずかな差は、この特定の子宮頸部損傷のマウスモデルを生成する別の研究者の間で観察することができる。呼吸器の出力にC2 SCIの効果は、第ポーター14によって1895年に記載された。子宮頸片側切断サイレント横隔神経活動とその後のダイヤフラムの麻痺につながる、損傷の同側（脳幹にrVRGにあり、 図1（a））、その中央のドライブから横隔運動ニューロンの求心路遮断を誘導する。反対側はそのまま残り、動物が生き残ることができます。下脊髄分節（C4レベル15で例えば挫傷の傷害）に位置する異なるSCIとは異なり、両方の側で横隔運動ニューロン核の完全性が維持されます。 CERVの後iCalのC2の損傷、いくつかの自発的な活動は、分節レベルC3〜C6（クロス横隔経路、CPP、 図1B）で、脊髄正中線を越えて反対側のサイレントシナプス経路の活性化を（横隔膜と横隔膜）同側で観測することができます。定義上、あるCPPの活性化、同側の部分横隔膜神経の回復を誘導対側横隔神経切断術と組み合わせたC2片側切断は、時間から数週間の損傷後16〜18を発生することがあります。呼吸の回復でこのCPP経路の本当の有益な効果は19制限されており、さらなる調査と治療は、自発的な回復3の大きさを改善するために開発されるべきである。 このプロトコルは、（前と横隔運動ニューロン、介在ニューロン、分子·蜂巣から呼吸生理学、様々なレベルでの呼吸ポスト病変可塑性を研究するための前臨床マウスモデルの強力なタイプが用意されていますR、例えば前肢）の運動だけでなく、C2は、部​​分的頸髄損傷後の呼吸器および運動回復を改善することを目的とした侵襲的·非侵襲的な治療戦略をテストするためのモデル。

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			<td>Fine Science Tool</td>
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			<td>Centravet</td>
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			<td>Fine Science Tool</td>
			<td>18000-45</td>
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			<td height="21" style="height:21px;">Catheter&#160;</td>
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			<td>MIR011</td>
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			<td height="21" style="height:21px;">Lactated Ringers</td>
			<td>Centravet</td>
			<td>RIN020</td>
			<td></td>
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			<td>Centravet</td>
			<td></td>
			<td></td>
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			<td>I1001M20R2A001</td>
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			<td height="21" style="height:21px;">683 RodentT Ventilator 115/230V</td>
			<td>Havard Apparatus</td>
			<td>55-0000</td>
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			<td height="21" style="height:21px;">Stand-Alone Vaporizer</td>
			<td>WPI</td>
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			<td>WPI</td>
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			<td>VET066</td>
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a murine model of cervical spinal cord injury to study post-lesional respiratory neuroplasticity

子宮頸部脊髄損傷は永久的な麻痺を誘導し、しばしば呼吸困難をもたらす。現在まで、効率的な治療薬は、高子宮頸部脊髄損傷（SCI）は、次の呼吸不全を改善/向上させるために開発されていない。ここでは、多様なポスト病変呼吸神経可塑性を研究するために、子宮頸部2（C2）メタメリックレベルの高い、SCIのマウス前臨床モデルを提案する。技術は、脳幹に位置して呼吸中枢からの横隔運動ニューロンの求心路遮断にダイヤフラムのhemiparalysisを誘発するC2レベルの外科部分の損傷、から構成されています。損傷の反対側はそのまま残り、動物の回復を可能にする。 （胸部と腰部のレベルで）運動機能に影響を与える他のSCIと異なり、呼吸機能は、動物のモチベーションを必要とせず、欠陥/回復の定量化が容易に（横隔膜と横隔膜神経記録を行うことができますS、全身換気）。この前臨床C2のSCIモデル（生理学、分子）の異なるレベルでの様々な呼吸器および非呼吸神経可塑性の事象を研究し、中に呼吸が向上する可能性があり、多様な推定の治療戦略をテストするために、強力で便利、そして信頼性の前臨床モデルであるSCI患者。

傷害の程度 成功と、この特定の実験モデルの再現性は、各マニピュレータ/外科医の経験に依存している。 C2は損傷後の呼吸の回復（横隔神経活動と横隔膜活性）のその後の量は、残りの腹と相関している白質21を免れる。怪我が「手作り」で、外科医からのいくつかの練習を必要とするので、それぞれのけがの程度は正確なサイズを決定するために...

Watch this Scientific Journal Video about A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity at JoVE.com

A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity

呼吸不全は、子宮頸部脊髄損傷後の死亡の主要な原因である。部分的な頚椎損傷によって誘発される呼吸不全の、再現性の定量化、および信頼性の前臨床動物モデルを持つことは、その後の呼吸器および非呼吸神経可塑性を理解するのに役立つと推定される補修戦略をテストすることができます。

ポスト病変呼吸神経可塑性を研究するための子宮頸脊髄損傷のマウスモデル

A cervical spinal cord injury induces permanent paralysis, and often leads to respiratory distress. To date, no efficient therapeutics have been developed ...

a-murine-model-cervical-spinal-cord-injury-to-study-post-lesional

Research

JoVE Journal

Medicine

13.4K ビュー.  Université de Versailles Saint-Quentin-en-Yvelines. 呼吸不全は、子宮頸部脊髄損傷後の死亡の主要な原因である。部分的な頚椎損傷によって誘発される呼吸不全の、再現性の定量化、および信頼性の前臨床動物モデルを持つことは、その後の呼吸器および非呼吸神経可塑性を理解するのに役立つと推定される補修戦略をテストすることができます。 

ビデオ: A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity

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) ...

医学

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 Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of spinal cord injury (SCI) in which the thoracic spinal cord is injured. Additionally, because most human cord injuries occur as the result of blunt, non-penetrating trauma (e.g. motor vehicle accident, sporting injury) where the spinal cord is violently struck by displaced bone or soft tissues, the majority of SCI researchers are of the opinion that the most clinically relevant injury models are those in which the spinal cord is rapidly contused.1 Therefore, an important step in the preclinical evaluation of novel treatments on their way to human translation is an assessment of their efficacy in a model of contusion SCI within the cervical spinal cord. Here, we describe the technical aspects and resultant anatomical and behavioral outcomes of an unilateral contusive model of cervical SCI that employs the Infinite Horizon spinal cord injury impactor.
Sprague Dawley rats underwent a left-sided unilateral laminectomy at C5. To optimize the reproducibility of the biomechanical, functional, and histological outcomes of the injury model, we contused the spinal cords using an impact force of 150 kdyn, an impact trajectory of 22.5&deg; (animals rotated at 22.5&deg;), and an impact location off of midline of 1.4 mm. Functional recovery was assessed using the cylinder rearing test, horizontal ladder test, grooming test and modified Montoya's staircase test for up to 6 weeks, after which the spinal cords were evaluated histologically for white and grey matter sparing.
The injury model presented here imparts consistent and reproducible biomechanical forces to the spinal cord, an important feature of any experimental SCI model. This results in discrete histological damage to the lateral half of the spinal cord which is largely contained to the ipsilateral side of injury. The injury is well tolerated by the animals, but does result in functional deficits of the forelimb that are significant and sustained in the weeks following injury. The cervical unilateral injury model presented here may be a resource to researchers who wish to evaluate potentially promising therapies prior to human translation.

A reliable and repeatable way to produce a cervical unilateral spinal cord injury using the Infinite Horizon impactor is described. The method takes advantage of a custom designed frame and clamp to stabilize the spine. The standardized procedure and biomechanical injury parameters result in sufficient and sustained injuries.

無限の地平線インパクターを用いた片側頚髄損傷の打撲のモデル

While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of ...

Controlled Cervical Laceration Injury in Mice

Use of genetically modified mice enhances our understanding of molecular mechanisms underlying several neurological disorders such as a spinal cord injury (SCI). Freehand manual control used to produce a laceration model of SCI creates inconsistent injuries often associated with a crush or contusion component and, therefore, a novel technique was developed. Our model of cervical laceration SCI has resolved inherent difficulties with the freehand method by incorporating 1) cervical vertebral stabilization by vertebral facet fixation, 2) enhanced spinal cord exposure, and 3) creation of a reproducible laceration of the spinal cord using an oscillating blade with an accuracy of &plusmn;0.01 mm in depth without associated contusion. Compared to the standard methods of creating a SCI laceration such as freehand use of a scalpel or scissors, our method has produced a consistent lesion. This method is useful for studies on axonal regeneration of corticospinal, rubrospinal, and dorsal ascending tracts.

A novel technique to create a reproducible in vivo model of cervical spinal cord laceration injury in the mouse is described. This technique is based on spine stabilization by fixation of the cervical facets and laceration of the spinal cord using an oscillating blade with an accuracy of &plusmn;0.01 mm.

マウスで制御子宮裂傷の傷害

Use of genetically modified mice enhances our  understanding of molecular mechanisms underlying several neurological disorders  such as a spinal cord ...

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 ...

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 ...

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 ...

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury

Spinal cord injuries (SCI) cause serious neurological impairment and psychological, economic, and social consequences for patients and their families. Clinically, more than 50% of SCI affect the cervical spine1. As a consequence of the primary injury, a cascade of secondary mechanisms including inflammation, apoptosis, and demyelination occur finally leading to tissue scarring and development of intramedullary cavities2,3. Both represent physical and chemical barriers to cell transplantation, integration, and regeneration. Therefore, shaping the inhibitory environment and bridging cavities to create a supportive milieu for cell transplantation and regeneration is a promising therapeutic target4. Here, a contusion/compression model of cervical SCI using an aneurysm clip is described. This model is more clinically relevant than other experimental models, since complete transection or ruptures of the cord are rare. Also in comparison to the weight drop model, which in particular damage the dorsum columns, circumferential compression of the spinal cord appears advantageous. Clip closing force and duration can be adjusted to achieve different injury severity. A ring spring facilitates precise calibration and constancy of clip force. Under physiological conditions, synthetic self-assembling peptides (SAP) self-assemble into nanofibers and thus, are appealing for application in SCI5. They can be injected directly into the lesion minimizing damage to the cord. SAPs are biocompatible structures erecting scaffolds to bridge intramedullary cavities and thus, equip the damaged cord for regenerative treatments. K2(QL)6K2 (QL6) is a novel SAP introduced by Dong et al.6 In comparison to other peptides, QL6 self-assembles into &#946;-sheets at neutral pH6.14 days after SCI, after the acute stage, SAPs are injected into the center of the lesion and neural precursor cells (NPC) are injected into adjacent dorsal columns. In order to support cell survival, transplantation is combined with continuous subdural administration of growth factors by osmotic micro pumps for 7 days.

Treating cervical spinal cord injury with both self-assembling peptides (SAP) and neural precursor cells (NPC), together with growth factors, is a promising approach to promote regeneration and recovery. A contusion/compression aneurysm clip rat model of cervical SCI and combined treatment involving SAP injection and NPC transplantation is established.

実験的子宮頸脊髄損傷における神経前駆細胞と自己組織化ペプチドの相乗使用

Spinal cord injuries (SCI) cause serious neurological impairment and psychological, economic, and social consequences for patients and their families. ...

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 ...