この作業は、脳損傷の研究でニュージャージー州委員会によって運営されている。

<ol>
	<li>Cernak, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+head+trauma.">Animal models of head trauma.</a> NeuroRx. 2, 410-422 (2005).</li><li>Reilly, P. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brain+injury:+the+pathophysiology+of+the+first+hours.'Talk+and+Die+revisited'.">Brain injury: the pathophysiology of the first hours.'Talk and Die revisited'.</a> J Clin Neurosci. 8, 398-403 (2001).</li><li>Hovda, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+increase+in+local+cerebral+glucose+utilization+following+fluid+percussion+brain+injury+is+prevented+with+kynurenic+acid+and+is+associated+with+an+increase+in+calcium.">The increase in local cerebral glucose utilization following fluid percussion brain injury is prevented with kynurenic acid and is associated with an increase in calcium.</a> Acta neurochir. 51, 331-333 (1990).</li><li>Whiting, M. D., Baranova, A. I., Hamm, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Cognitive Impairment following Traumatic Brain Injury, Animal Models of Cognitive Impairment. , (2006).</li><li>McIntosh, T. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Traumatic+brain+injury+in+the+rat:+characterization+of+a+lateral+fluid-percussion+model.">Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model.</a> Neuroscience. 28, 233-244 (1989).</li><li>Adams, J. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diffuse+axonal+injury+in+head+injury:+definition,+diagnosis+and+grading.">Diffuse axonal injury in head injury: definition, diagnosis and grading.</a> Histopathology. 15, 49-59 (1989).</li><li>Cordobes, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Post-traumatic+diffuse+axonal+brain+injury.+Analysis+of+78+patients+studied+with+computed+tomography.">Post-traumatic diffuse axonal brain injury. Analysis of 78 patients studied with computed tomography.</a> Acta Neurochir. 81, 27-35 (1986).</li><li>Maxwell, W. L., Povlishock, J. T., Graham, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+mechanistic+analysis+of+nondisruptive+axonal+injury:+a+review.">A mechanistic analysis of nondisruptive axonal injury: a review.</a> J Neurotrauma. 14, 419-440 (1997).</li><li>Lighthall, J. W., Anderson, T. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The neurobiology of cenral nervous system trauma. , 3-12 (1994).</li><li>Marcoux, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Persistent+metabolic+crisis+as+measured+by+elevated+cerebral+microdialysis+lactate-pyruvate+ratio+predicts+chronic+frontal+lobe+brain+atrophy+after+traumatic+brain+injury.">Persistent metabolic crisis as measured by elevated cerebral microdialysis lactate-pyruvate ratio predicts chronic frontal lobe brain atrophy after traumatic brain injury.</a> Crit Care Med. 36, 2871-2877 (2008).</li><li>McIntosh, T. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuropathological+sequelae+of+traumatic+brain+injury:+relationship+to+neurochemical+and+biomechanical+mechanisms.">Neuropathological sequelae of traumatic brain injury: relationship to neurochemical and biomechanical mechanisms.</a> Lab Invest. 74, 315-342 (1996).</li><li>Morganti-Kossmann, M. C., Satgunaseelan, L., Bye, N., Kossmann, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+immune+response+by+head+injury.">Modulation of immune response by head injury.</a> Injury. 38, 1392-1400 (2007).</li><li>Capruso, D. X., Levin, H. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+impairment+following+closed+head+injury.">Cognitive impairment following closed head injury.</a> Neurol Clin. 10, 879-893 (1992).</li><li>Levin, H. S., Goldstein, F. C., High, W. M., Eisenberg, H. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Disproportionately+severe+memory+deficit+in+relation+to+normal+intellectual+functioning+after+closed+head+injury.">Disproportionately severe memory deficit in relation to normal intellectual functioning after closed head injury.</a> J Neurol Neurosurg Psychiatry. 51, 1294-1301 (1988).</li><li>Kabadi, S. V., Hilton, G. D., Stoica, B. A., Zapple, D. N., Faden, A. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluid-percussion-induced+traumatic+brain+injury+model+in+rats.">Fluid-percussion-induced traumatic brain injury model in rats.</a> Nat Protoc. 5, 1552-1563 (2010).</li><li>Cherian, L., Robertson, C. S., Contant, C. F., Bryan, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lateral+cortical+impact+injury+in+rats:+cerebrovascular+effects+of+varying+depth+of+cortical+deformation+and+impact+velocity.">Lateral cortical impact injury in rats: cerebrovascular effects of varying depth of cortical deformation and impact velocity.</a> J Neurotrauma. 11, 573-585 (1994).</li><li>Dixon, C. E., Clifton, G. L., Lighthall, J. W., Yaghmai, A. A., Hayes, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+controlled+cortical+impact+model+of+traumatic+brain+injury+in+the+rat.">A controlled cortical impact model of traumatic brain injury in the rat.</a> J Neurosci Methods. 39, 253-262 (1991).</li><li>Flierl, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+closed+head+injury+model+induced+by+a+weight-drop+device.">Mouse closed head injury model induced by a weight-drop device.</a> Nat Protoc. 4, 1328-1337 (2009).</li><li>Lifshitz, J., Chen, J., Xu, Z. C., Xu, X. -. M., Zhang, J. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chapter+32.">Chapter 32.</a> Animal Models of Acute Neurological Injuries. , 369-384 (2008).</li><li>Thompson, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lateral+fluid+percussion+brain+injury:+a+15-year+review+and+evaluation.">Lateral fluid percussion brain injury: a 15-year review and evaluation.</a> J Neurotrauma. 22, 42-75 (2005).</li><li>Hamm, R. J., Pike, B. R., O'Dell, D. M., Lyeth, B. G., Jenkins, L. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+rotarod+test:+an+evaluation+of+its+effectiveness+in+assessing+motor+deficits+following+traumatic+brain+injury.">The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury.</a> J Neurotrauma. 11, 187-196 (1994).</li><li>Scherbel, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+acute+and+chronic+responses+of+tumor+necrosis+factor-deficient+mice+to+experimental+brain+injury.">Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury.</a> Proc Natl Acad Sci. 96, 8721-8726 (1999).</li><li>Morris, R. G., Garrud, P., Rawlins, J. N., O'Keefe, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Place+navigation+impaired+in+rats+with+hippocampal+lesions.">Place navigation impaired in rats with hippocampal lesions.</a> Nature. 297, 681-683 (1982).</li><li>Stichel, C. C., Muller, H. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+CNS+lesion+scar:+new+vistas+on+an+old+regeneration+barrier.">The CNS lesion scar: new vistas on an old regeneration barrier.</a> Cell Tissue Res. 294, 1-9 (1998).</li><li>Brechot, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+macrophage+activation+state+protects+tissue+from+necrosis+during+critical+limb+ischemia+in+thrombospondin-1-deficient+mice.">Modulation of macrophage activation state protects tissue from necrosis during critical limb ischemia in thrombospondin-1-deficient mice.</a> PLoS One. 3, e3950-e3950 (2008).</li><li>Lifshitz, J., Witgen, B. M., Grady, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+cognitive+impairment+after+lateral+fluid+percussion+brain+injury+recovers+by+1+month:+evaluation+by+conditioned+fear+response.">Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: evaluation by conditioned fear response.</a> Behav Brain Res. 177, 347-357 (2007).</li><li>Thompson, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+evaluation+of+traumatically+brain-injured+rats+using+serial+testing+in+the+Morris+water+maze.">Cognitive evaluation of traumatically brain-injured rats using serial testing in the Morris water maze.</a> Restor Neurol Neurosci. 24, 109-114 (2006).</li><li>Doll, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharyngeal+selective+brain+cooling+improves+neurofunctional+and+neurocognitive+outcome+after+fluid+percussion+brain+injury+in+rats.">Pharyngeal selective brain cooling improves neurofunctional and neurocognitive outcome after fluid percussion brain injury in rats.</a> Journal of neurotrauma. 26, 235-242 (2009).</li><li>Fujimoto, S. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+and+cognitive+function+evaluation+following+experimental+traumatic+brain+injury.">Motor and cognitive function evaluation following experimental traumatic brain injury.</a> Neuroscience and biobehavioral reviews. 28, 365-378 (2004).</li><li>Carbonell, W. S., Maris, D. O., McCall, T., Grady, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adaptation+of+the+fluid+percussion+injury+model+to+the+mouse.">Adaptation of the fluid percussion injury model to the mouse.</a> Journal of neurotrauma. 15, 217-229 (1998).</li></ol>

利害の衝突は宣言されません。

LFPの方法は、ここで紹介のneuropathalogicalと行動の成果の多くのモデルは、TBIの広く使用されている動物モデルとなった理由である外傷性脳損傷の軽度から中等度。この手法の妥当性と信頼性を向上させるために考慮すべきいくつかの重要なステップがあります。例えば、硬膜の完全性がクレイニエクトミ中に危険にさらされていないだけで、動物がLFPに供し、研究で使用することが重要です。クレイニエクトミは、任意の接着剤やセメントによって閉塞されている場合、さらに、クレイニエクトミ下硬膜のように一部が流体圧の力にさらされていない、動物は試験から除外されるべきである。最後に、立ち直り反射の時間や死亡率が所望の範囲内にない場合、動物は研究に含まれるべきではない。圧力パルスの強度は、より深刻な怪我を生成するために増加することができます。 図1に示すように、LFPデバイスの設定は比較的単純で、傷害の程度の再現性は、オシロスコープに圧力の雰囲気を監視することによって維持されています。オシロスコープのトレース上の曲線の滑ら​​かな形状は、LFPの傷害の誘導を妨害する可能性流体内に気泡がないことを示しています。テストパルスは、傷害を誘発する前に配信される必要がありますし、オシロスコープのトレースは、滑らかな曲線を示していない場合、気泡を削除する必要があります。パルスの持続時間は、衝突試験のシミュレーションで測定された誘導の時間を表す約20ミリ秒です。短いパルスの傷害はより多くの焦点怪我を生産する可能性があります。 TBIしたがって、パルスのモデルのこの期間は人間。 LFPを以下の形態学的および細胞の変化は、組織への物理的な損傷だけでなく、図2に示すようにアストロサイトとマクロファージ数の増加が含まれています。それは傷害の顕著な兆候の一つは、星状膠細胞とグリア瘢痕の形成の過形成であることが十分に確立されている。グリア瘢痕が有益と有害な影響24の両方を有することが示されている。同様に、マクロファージは、治癒のプロセスが25を開始したとき、位相は、次の怪我の間に様々な組織に蓄積することが知られている。このように偽のコントロールに対する相対LFP試料のGFAPとMAC​​1陽性細胞数の増加は、傷害の誘導の指標である。偽のコントロールで、これらの細胞特異的マーカーの発現の欠如は、単独で手術操作は脳組織の健康上およびタンパク質発現の変化は、傷害のパラダイムに固有の負の結果を持っていないことを示しています。 図3に示す軽度のLFPの行動結果は、認知や運動障害などがあります。 MWMの所見LFPマウスは、最終的にタスクを学ぶことを示しているが偽のマウスよりも遅い速度で、彼らは訓練の後だけでなく、一日の作業を覚えていません。このように、さらに軽度負傷マウスは、その後のテスト中に取得する必要が空間的な情報を、処理の統合、および格納するための外部手がかりを使ってで偽のマウスよりも効率的です。このような条件性恐怖反応のような他の海馬依存の認知タスクはLFP 26に受けたマウスでは損なわれることが示されている。最後に、軽度の損傷後の3週間にロータロッドパラダイムで偽のマウスの相対LFPマウスによって落下する短い待ち時間は、統合されたvestibulomotorと感覚運動機能の障害の指標です。他のグループ27から30によって示されているとして、より多くの中程度の傷害は、認知および運動機能のより顕著な変化を明らかにするだろう。 それが予想される基準の多くを満たしているため合計では、LFPは人間TBIの有効なモデルです。 LFPは、構成概念妥当性を提供するという点では、ヒトにおけるTBI誘導病因のプロセスを再作成します。具体的には、力と死亡率の大きさは、事前に怪我の外科的介入は、動物モデルに対して一意であることを警告と軽度および中等度のスポーツカー関連の負傷で発生しているものと同様である。 LFPはまた、人間のTBIで観測された解剖学的、生化学的、神経病理学的および行動への影響の多くのそのLFP反復するに顔の妥当性を示す。そこにLFP後に検出される焦点とびまん性変化の両方があり、インパクトの左右差は1つが対側のそれと怪我に同側での形態学的損傷を比較することができます。一つ注意点は、認知運動効果を1つだけの半球が負傷の結果として、より微妙な場合があることである。最後に、LFPは、予測的妥当性を示し、LFPの手法の信頼性は、傷害20の誘導の前または後に様々な薬理学的および遺伝的操作の評価が可能になります。このような血圧、血液のpHや血液などの生理学的変数ガスは、治療薬の作用機序を決定するために、テスト薬剤の存在下および非存在下で測定する必要があります。しかし、TBIのプライマリとセカンダリの影響の複雑な性質のため、それはすべての症状を緩和することができる単一の介入を識別することは困難な作業です。 LFPのテクニックの一つ将来の考慮事項は、流体15の振り子によって提供される力を校正するための必要性をなくし、そのような気泡のような運用上の変数を避けるために、マイクロプロセッサ制御、空気圧駆動機器を採用したマイクロ流体パーカッションの使用可能性があります。しかし、標準のLFPのアプローチは、より良い介入や治療につながるTBI以下のダメージと回復の分子メカニズムを探索するために信頼性とシンプルな手法であることが多くの研究者によって証明されています。

<ul><li>マウスの定位アライメント測定器（Kopfはインスツルメンツ） </li><li>マウスのガス麻酔ヘッドホルダー（Kopfはインスツルメンツ） </li><li> O 2フラッシュ（パークランドサイエンティフィック）と麻酔器</li><li> O2フラッシュ（パークランドサイエンティフィック）と麻酔器</li><li> Buprenorphrine（ウェブスターの動物の供給） </li><li>リフレッシュLacri潤滑眼軟膏（フィッシャー） </li><li>ブピバカイン/ Marcaine（ウェブスターの動物の供給） </li><li>ポビドン - ヨウ素溶液（フィッシャー） </li><li> 20グラム1 ½&quot;針（Becton Dickinson社製） </li><li>手術用メスの刃（＃15）とホルダー（ベクトンディッキンソン） </li><li>ブルドッグクランプ（ファイン科学のツール） </li><li>歯科用ツールや骨のスクレーパー（ファイン科学のツール） </li><li>鉗子デュモンを把握する側＃6（ファイン科学のツール） </li><li> 3ミリメートル外径トレフィン（研究の計装屋、ペンシルバニア大学） </li><li>固体ナイロンコード（1.7mmの直径、例えば雑草トリマーライン） </li><li>スーパー接着剤ゲル</li><li>ロックタイトシアノアクリレート接着剤（ロックタイト444徳パック）（ヘンケル株式会社） </li><li>ジェットアクリルリキッド（バトラーシャイン） </li><li>パーマの新しい線を引く/修理樹脂（バトラーシャイン） </li><li>ストレージオシロスコープTDS 1001B、40 MHzの、500ミリ/秒（テクトロニクス） </li><li>外傷デューサ圧力トランスデューサアンプ（カスタム設計と製作、バージニアコモンウェルス大学） </li><li> LFPデバイス（カスタム設計と製作、バージニアコモンウェルス大学） </li><li>高圧チューブ、長さ41センチメートル、ボリューム2ミリリットル（バクスター） </li><li> 3M Vetbond組織接着剤（フィッシャー） </li></ul>

lateral fluid percussion: model of traumatic brain injury in mice

外傷性脳損傷（TBI）の研究では、どの罹患率と死亡率の結果頭部外傷の意識の高まりにより、新たな勢いを、達成している。再生のプロセスの1,2に続いているTBI、複雑かつ異種の二次影響の結果、以下の一次的損傷の性質に基づく。一次的損傷は、頭蓋骨の骨折からまたはせん断と動き3,4に起因する脳の変位を引き起こす組織の伸張から脳への直接挫傷により誘導され得る。結果として得られる血腫と裂傷が血管反応3,5を引き起こす、と白質の形態学的および機能的な損傷は、軸索傷害6-8拡散につながる。一般的に脳に見られる追加の二次的変化は、浮腫や頭蓋内圧亢進9です。 TBIは、次の最終的に長期的な神経学的障害を13,14につながる興奮神経伝達物質、免疫メディエーターおよび酸素ラジカル10-12、の放出に関与する生化学および生理学的経路の微視的な変化があります。したがって、ヒトおよびげっ歯類に存在する同様の細胞や分子のイベントはTBIそのTBIの適切な動物モデルを選択すると、損傷および修復のメカニズムを研究するために重要です。 流体パーカッション、皮質への影響及び重量落下/衝撃加速度1：TBIの様々な実験モデルはヒトで観察TBIの局面を再現するために開発されている、それらの間の3つの特定のモデルが広くげっ歯類に適応されています。流体のパーカッションのデバイスは、そのまま硬膜への簡単な流体の圧力パルスを印加することによりクレイニエクトミによって傷害を生成します。パルスは、流体のリザーバーのピストンを打つ振り子によって作成されます。パーカッションは、神経組織1,15の簡単な変位や変形を生成します。逆に、皮質衝撃傷害は、空気圧16,17の下で厳格なインパクターを経由して無傷の硬膜への機械的エネルギーを提供します。重量落下/衝撃モデルは閉じた頭蓋骨18日に特定の質量を持つ棒の落下によって特徴付けられる。 TBIのモデルの中で、LFPは混合焦点とびまん性脳損傷19を評価するために最も確立されたと一般的に使用されるモデルです。それは再現可能であり、傷害のパラメータの操作を可能にするために標準化されています。 LFPの反復するの怪我は、このように、それが臨床的に関連するレンダリング、ヒトで観察し、臨床翻訳20の新規治療薬の探索が可能になります。 我々は、マウスでLFPの手順を実行するための詳細なプロトコルを記述する。与えた損傷は皮質、海馬および最も脆弱である脳梁のような脳の領域で、軽度から中等度です。海馬と運動学習のタスクは、LFPは、次の探索されます。

Watch this Scientific Journal Video about Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice at JoVE.com

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

横方向の流体パーカッション（LFP）、マウスの外傷性脳損傷の確立されたモデルは、実証される。妥当性、信頼性と臨床的関連：LFPは、動物モデルの3つの主要な基準を満たしています。外科的開頭で構成される手順は、ハブの固定は、焦点とびまん性傷害の結果、傷害の誘導が続く記述されています。

横方向の流体のパーカッション：マウスにおける外傷性脳損傷のモデル

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and ...

lateral-fluid-percussion-model-of-traumatic-brain-injury-in-mice

Nanyang Technological University

Research

JoVE Journal

Neuroscience

40.4K ビュー.  University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School. 横方向の流体パーカッション（LFP）、マウスの外傷性脳損傷の確立されたモデルは、実証される。妥当性、信頼性と臨床的関連：LFPは、動物モデルの3つの主要な基準を満たしています。外科的開頭で構成される手順は、ハブの固定は、焦点とびまん性傷害の結果、傷害の誘導が続く記述されています。

ビデオ: Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

A Method to Inflict Closed Head Traumatic Brain Injury in Drosophila

Traumatic brain injury (TBI) affects millions of people each year, causing impairment of physical, cognitive, and behavioral functions and death. Studies using Drosophila have contributed important breakthroughs in understanding neurological processes. Thus, with the goal of understanding the cellular and molecular basis of TBI pathologies in humans, we developed the High Impact Trauma (HIT) device to inflict closed head TBI in flies. Flies subjected to the HIT device display phenotypes consistent with human TBI such as temporary incapacitation and progressive neurodegeneration. The HIT device uses a spring-based mechanism to propel flies against the wall of a vial, causing mechanical damage to the fly brain. The device is inexpensive and easy to construct, its operation is simple and rapid, and it produces reproducible results. Consequently, the HIT device can be combined with existing experimental tools and techniques for flies to address fundamental questions about TBI that can lead to the development of diagnostics and treatments for TBI. In particular, the HIT device can be used to perform large-scale genetic screens to understand the genetic basis of TBI pathologies.

A Method to Inflict Closed Head Traumatic Brain Injury in Drosophila

Here we describe a method to inflict closed head traumatic brain injury (TBI) in Drosophila. This method provides a gateway to investigate the cellular and molecular mechanisms that underlie TBI pathologies using the vast array of experimental tools and techniques available for flies.

で閉鎖性頭部外傷性脳損傷を負わせる方法<em&gt;ショウジョウバエ</em

Traumatic brain injury (TBI) affects millions of people each year, causing impairment of physical, cognitive, and behavioral functions and death. Studies ...

神経科学

Imaging Neural Activity in the Primary Somatosensory Cortex Using Thy1-GCaMP6s Transgenic Mice

The mammalian brain exhibits marked symmetry across the sagittal plane. However, detailed description of neural dynamics in symmetric brain regions in adult mammalian animals remains elusive. In this study, we describe an experimental procedure for measuring calcium dynamics through dual optical windows above bilateral primary somatosensory corticies (S1) in Thy1-GCaMP6s transgenic mice using 2-photon (2P) microscopy. This method enables recordings and quantifications of neural activity in bilateral mouse brain regions one at a time in the same experiment for a prolonged period in vivo. Key aspects of this method, which can be completed within an hour, include minimally invasive surgery procedures for creating dual optical windows, and the use of 2P imaging. Although we only demonstrate the technique in the S1 area, the method can be applied to other regions of the living brain facilitating the elucidation of structural and functional complexities of brain neural networks.

Imaging Neural Activity in the Primary Somatosensory Cortex Using Thy1-GCaMP6s Transgenic Mice

We describe an experimental procedure for measuring neuronal activity through dual optical windows above bilateral primary somatosensory corticies (S1) in Thy1-GCaMP6s transgenic mice using 2-photon (2P) microscopy in vivo.

Thy1を用いた一次体性感覚野における神経活動のイメージング-GCaMP6s トランスジェニック マウス

The mammalian brain exhibits marked symmetry across the sagittal plane. However, detailed description of neural dynamics in symmetric brain regions in ...

Automated Gait Analysis in Mice with Chronic Constriction Injury

The von Frey test is a classical method that has been widely used to examine the sensory function of neuropathic pain animals. However, it has some disadvantages such as subjective data and the requirement of a skilled, experienced experimenter. To date, a variety of modifications have improved the von Frey method, but it still has a few limitations. Recent reports have suggested that gait analysis produces more accurate and objective data from the neuropathic animals. This protocol demonstrates how to perform the automated gait analysis to determine the degree of neuropathic pain in mice. After several days of acclimation, the mice were allowed to walk freely on the glass floor to illuminate footprints. Then, quantification of the footprints and gait were performed through video clips with automatic analysis of various walking parameters, such as area of paw print, swing time, angle of paw, etc.
The main purpose of this study is to describe the methodology of automated gait analysis and briefly compare it with data from the classical sensory test using von Frey filament.

The precise assessment of pain response in a neuropathic animal model is critical to investigate the pathophysiology of pain diseases and develop new analgesics. We present a sensitive and objective method to determine the sensory function of the rodent hind paw by an automated gait analysis system.

絞扼性損傷マウス自動歩行分析

The von Frey test is a classical method that has been widely used to examine the sensory function of neuropathic pain animals. However, it has some ...

A Novel In Vitro Model of Blast Traumatic Brain Injury

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the detonation of explosive devices, however, the mechanisms that underlie the brain damage resulting from blast overpressure exposure are not entirely understood and are believed to be unique to this type of brain injury. Preclinical models are crucial tools that contribute to better understand blast-induced brain injury. A novel in vitro blast TBI model was developed using an open-ended shock tube to simulate real-life open-field blast waves modelled by the Friedlander waveform. C57BL/6N mouse organotypic hippocampal slice cultures were exposed to single shock waves and the development of injury was characterized up to 72 h using propidium iodide, a well-established fluorescent marker of cell damage that only penetrates cells with compromised cellular membranes. Propidium iodide fluorescence was significantly higher in the slices exposed to a blast wave when compared with sham slices throughout the duration of the protocol. The brain tissue injury is very reproducible and proportional to the peak overpressure of the shock wave applied.

A Novel In Vitro Model of Blast Traumatic Brain Injury

This paper describes a novel model of primary blast traumatic brain injury. A compressed-air driven shock tube is used to expose in vitro mouse hippocampal slice cultures to a single shock wave. This is a simple and rapid protocol generating a reproducible brain tissue injury with a high throughput.

爆発外傷性脳損傷の新規In Vitroモデル

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the ...

Effects of Blast-induced Neurotrauma on Pressurized Rodent Middle Cerebral Arteries

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral vascular effects. Impact (i.e., non-blast) traumatic brain injury (TBI) is known to decrease pressure autoregulation in the cerebral vasculature in both humans and experimental animals. The hypothesis that blast-induced traumatic brain injury (bTBI), like impact TBI, results in impaired cerebral vascular reactivity was tested by measuring myogenic dilatory responses to reduced intravascular pressure in rodent middle cerebral arterial (MCA) segments from rats subjected to mild bTBI using an Advanced Blast Simulator (ABS) shock tube. Adult, male Sprague-Dawley rats were anesthetized, intubated, ventilated and prepared for Sham bTBI (identical manipulation and anesthesia except for blast injury) or mild bTBI. Rats were randomly assigned to receive Sham bTBI or mild bTBI followed by sacrifice 30 or 60 min post-injury. Immediately after bTBI, righting reflex (RR) suppression times were assessed, euthanasia at the time points post-injury was completed, the brain was harvested and the individual MCA segments were collected, mounted and pressurized. As the intraluminal pressure perfused through the arterial segments was reduced in 20 mmHg increments from 100 to 20 mmHg, MCA diameters were measured and recorded. With decreasing intraluminal pressure, MCA diameters steadily increased significantly above baseline in the Sham bTBI groups while MCA dilator responses were significantly reduced (p &#60; 0.05) in both bTBI groups as evidenced by the impaired, smaller MCA diameters recorded for the bTBI groups. In addition, RR suppression in the bTBI groups was significantly (p &#60; 0.05) higher than in the Sham bTBI groups. MCA&#39;s collected from the Sham bTBI groups exhibited typical vasodilatory properties to decreases in intraluminal pressure while MCA&#39;s collected following bTBI exhibited significantly impaired myogenic vasodilatory responses to reduced pressure that persisted for at least 60 min after bTBI.

Here, we present a protocol to describe methods for ex vivo vascular reactivity determination following a primary blast traumatic brain injury (bTBI) using isolated, pressurized, rodent middle cerebral arterial (MCA) segments. bTBI induction is accomplished using a shock tube, also known as an Advanced Blast Simulator (ABS) device.

加圧齧歯動物に及ぼす影響の爆発による頭部外傷の中間の大脳動脈

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral ...

Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also demonstrate that traumatic brain injuries cause changes to the gut microbiota. However, mechanisms underlying the bidirectional regulation of the brain-gut axis remain unknown. Currently, few models exist for studying the changes in gut microbiota after traumatic brain injury. Therefore, the presented study combines protocols for inducing traumatic brain injury using a lateral fluid percussion device and analysis of caecum samples following injury for investigating alterations in the gut microbiome. Alterations of the gut microbiota composition after traumatic brain injury are determined using 16S-rDNA sequencing. This protocol provides an effective method for studying the relationships between enteric microorganisms and traumatic brain injury.

Presented here is a protocol to induce diffuse traumatic brain injury using a lateral fluid percussion device followed by the collection of the caecum content for gut microbiome analysis.

マウスの外傷性脳損傷後のカエカム微生物叢の変化を調べている

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also ...

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous variability and heterogeneity (age, gender, type of trauma, other possible pathologies, etc.), animal models play a key role in unraveling factors that are limitations in clinical research. They provide a standardized and controlled setting to investigate the biological mechanisms of injury and repair following TBI. However, not all animal models mimic the diffuse and subtle nature of mTBI effectively. For example, the commonly used controlled cortical impact (CCI) and lateral fluid percussion injury (LFPI) models make use of a craniotomy to expose the brain and induce widespread focal trauma, which are not commonly seen in mTBI. Therefore, these experimental models are not valid to mimic mTBI. Thus, an appropriate model should be used to investigate mTBI. The Marmarou weight drop model for rats induces similar microstructural alterations and cognitive impairments as seen in patients who sustain mild trauma; therefore, this model was selected for this protocol. Conventional computed tomography and magnetic resonance imaging (MRI) scans commonly show no damage following a mild injury, because mTBI induces often only subtle and diffuse injuries. With diffusion weighted MRI, it is possible to investigate microstructural properties of brain tissue, which can provide more insight into the microscopic alterations following mild trauma. Therefore, the goal of this study is to obtain quantitative information of a selected region-of-interest (i.e., hippocampus) to follow up disease progression after obtaining a mild and diffuse brain injury.

The overall goal of this procedure is to obtain quantitative microstructural information of the hippocampus in a rat with mild traumatic brain injury. This is done using an advanced diffusion-weighted magnetic resonance imaging protocol and region-of-interest based analysis of parametric diffusion maps.

軽度の外傷性脳損傷を有するラットの海馬における高度な拡散イメージング

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous ...

Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the United States. In fact, TBI is a contributing factor to over a third of all injury-related mortality. Nonetheless, the cellular and molecular mechanisms underlying the pathophysiology of TBI are poorly understood. Thus, preclinical models of TBI capable of replicating the injury mechanisms pertinent to TBI in human patients are a critical research need. The controlled cortical impact (CCI) model of TBI utilizes a mechanical device to directly impact the exposed cortex. While no model can full recapitulate the disparate injury patterns and heterogeneous nature of TBI in human patients, CCI is capable of inducing a wide range of clinically applicable TBI. Furthermore, CCI is easily standardized allowing investigators to compare results across experiments as well as across investigative groups. The following protocol is a detailed description of applying a severe CCI with a commercially available impacting device in a murine model of TBI.

Here we describe a protocol for the induction of murine traumatic brain injury via an open-head controlled cortical impact.

外傷性脳損傷の誘導に対する制御された皮質影響のマウスモデル

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the ...

Low-intensity Blast Wave Model for Preclinical Assessment of Closed-head Mild Traumatic Brain Injury in Rodents

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of medical visits in the United States. There are currently no FDA-approved treatments available for TBI. The increased incidence of military-related, blast-induced TBI further accentuates the urgent need for effective TBI treatments. Therefore, new preclinical TBI animal models that recapitulate aspects of human blast-related TBI will greatly advance the research efforts into the neurobiological and pathophysiological processes underlying mild to moderate TBI as well as the development of novel therapeutic strategies for TBI.
Here we present a reliable, reproducible model for the investigation of the molecular, cellular, and behavioral effects of mild to moderate blast-induced TBI. We describe a step-by-step protocol for closed-head, blast-induced mild TBI in rodents using a bench-top setup consisting of a gas-driven shock tube equipped with piezoelectric pressure sensors to ensure consistent test conditions. The benefits of the setup that we have established are its relative low-cost, ease of installation, ease of use and high-throughput capacity. Further advantages of this non-invasive TBI model include the scalability of the blast peak overpressure and the generation of controlled reproducible outcomes. The reproducibility and relevance of this TBI model has been evaluated in a number of downstream applications, including neurobiological, neuropathological, neurophysiological and behavioral analyses, supporting the use of this model for the characterization of processes underlying the etiology of mild to moderate TBI.

We present here a protocol of a blast wave model for rodents to investigate neurobiological and pathophysiological effects of mild to moderate traumatic brain injury. We established a gas-driven, bench-top setup equipped with pressure sensors allowing for reliable and reproducible generation of blast-induced mild to moderate traumatic brain injury.

げっ歯類における閉鎖性軽度外傷性脳損傷の前臨床評価のための低強度ブラスト波モデル

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of ...

Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and understanding the mechanisms of how a TBI alters brain function. The availability of multiple animal models of TBI is necessary to model the different aspects and severities of TBI seen in people. This manuscript describes the use of a midline closed head injury (CHI) to develop a mouse model of mild TBI. The model is considered mild because it does not produce structural brain lesions based on neuroimaging or gross neuronal loss. However, a single impact creates enough pathology that cognitive impairment is measurable at least 1 month after injury. A step-by-step protocol to induce a CHI in mice using a stereotaxically guided electromagnetic impactor is defined in the paper. The benefits of the mild midline CHI model include the reproducibility of the injury-induced changes with low mortality. The model has been temporally characterized up to 1 year after the injury for neuroimaging, neurochemical, neuropathological, and behavioral changes. The model is complementary to open skull models of controlled cortical impact using the same impactor device. Thus, labs can model both mild diffuse TBI and focal moderate-to-severe TBI with the same impactor.

The protocol describes mild traumatic brain injury in a mouse model. In particular, a step-by-step protocol to induce a mild midline closed head injury and the characterization of the animal model is fully explained.

マウスにおける軽度外傷性脳損傷の電磁制御クローズドヘッドモデル

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and ...