この研究は、神経障害および脳卒中（MPB）に関する国立研究所のR01 NS067417によって支持された。

これらの研究は、国立研究所の保健所の実験動物のケアと使用に関するガイドの推奨事項に厳密に従って行った。このプロトコールは、ジョージタウン大学の動物実験および使用委員会の承認を受けた。マウスを温度制御された動物施設に収容し、12時間明/ 12時間暗サイクルで維持した。食べ物と水は自由に自由に入手できました 。 1. mTBI装置の準備注記：mTBI装置には、衝撃パラメータを制御するデータ収集（DAQ）ボックス、衝突を実行する高速空気圧インパクタ、衝撃後にヘッドを減速するための成形ゲル充填ベースが含まれています。 <ol><li>圧縮空気をオンにし、高速空気圧インパクターを861.85 kPaの圧力設定に初期化します。 </li><li> DAQ制御システムを、2.35 m / sのピストン速度、表面滞留時間eは31.5msである。 </li><li>正中線がインパクタ先端の軌跡と垂直になるように、成形ゲル充填ベース（圧縮率64kPa / mm）を配置します。 </li></ol> 2. mTBIインパクト<ol><li>使用するすべてのマウスの体重を記録する。 </li><li>誘導チャンバー内で120秒間、酸素中3％イソフルランでマウスを麻酔する。 </li><li>マウスをmTBI装置に移し、柔軟で固定されていないノーズコーンを介して麻酔を継続する。 </li><li>ノーズコーンでは、マウスパッドの頭をゲルパッドの上に置き、頭蓋骨の平らな表面がインパクターの先端に垂直になるようにします。 </li><li>テープをマウスの頭の上に置き、平らな面を作り、耳をインパクトサイトから離します。 </li><li>ポリテトラフルオロエチレンインパクターの先端を下げて、頭の中心にある矢状の中線に合わせます。使用されるインパクタ先端部は直径10mmであり、目の真後ろから耳の正中線までの頭皮の領域を覆う。インパクタを調整してjustがマウスの頭の表面に触れる。 </li><li>インパクターの先端を引っ込め、必要なたわみ深さ（7.5 mm）を手動でダイヤルします。 </li><li> DAQコントロールシステムをアームし、トリガボタンを押してマウスの頭部に影響を与えます（特異または反復のいずれかの影響）。反復的なインパクトは、各インパクトの間に遅延なしで連続して提供されます。 </li><li>最後のインパクトの直後に、マウスを麻酔およびmTBI装置から取り出し、仰臥位に置く。 </li><li>ストップウオッチを使用すると、右旋回の戻り（仰臥位から​​腹臥位へ）の戻り時間を測定し、意識の時間の損失、歩行までの時間（妨げられない歩行）を測定します。 </li><li>マウスをモニターし、正常な動作に回復すると、そのホームケージに戻ります。 </li><li>擬似マウスは、同じ取り扱いと麻酔を受けるが、影響はない。 </li></ol>

<ol>
	<li>McMahon, P., 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=Symptomatology+and+functional+outcome+in+mild+traumatic+brain+injury:+results+from+the+prospective+TRACK-TBI+study.">Symptomatology and functional outcome in mild traumatic brain injury: results from the prospective TRACK-TBI study.</a> J Neurotrauma. 31 (1), 26-33 (2014).</li><li>Barkhoudarian, G., Hovda, D. A., Giza, C. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+molecular+pathophysiology+of+concussive+brain+injury.">The molecular pathophysiology of concussive brain injury.</a> Clin Sports Med. 30 (1), 33-48 (2011).</li><li>Blennow, K., Hardy, J., Zetterberg, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+neuropathology+and+neurobiology+of+traumatic+brain+injury.">The neuropathology and neurobiology of traumatic brain injury.</a> Neuron. 76 (5), 886-899 (2012).</li><li>Levin, H. S., Diaz-Arrastia, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosis,+prognosis,+and+clinical+management+of+mild+traumatic+brain+injury.">Diagnosis, prognosis, and clinical management of mild traumatic brain injury.</a> Lancet Neurol. 14 (5), 506-517 (2015).</li><li>McCrory, P., 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=Consensus+statement+on+concussion+in+sport:+the+4th+International+Conference+on+Concussion+in+Sport,+Zurich,+November+2012.">Consensus statement on concussion in sport: the 4th International Conference on Concussion in Sport, Zurich, November 2012.</a> J Athl Train. 48 (4), 554-575 (2012).</li><li>Talavage, T. 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=Functionally-detected+cognitive+impairment+in+high+school+football+players+without+clinically-diagnosed+concussion.">Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion.</a> J Neurotrauma. 31 (4), 327-338 (2014).</li><li>Angoa-Perez, 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=Animal+models+of+sports-related+head+injury:+bridging+the+gap+between+pre-clinical+research+and+clinical+reality.">Animal models of sports-related head injury: bridging the gap between pre-clinical research and clinical reality.</a> J Neurochem. 129 (6), 916-931 (2014).</li><li>Creed, J. 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=Concussive+brain+trauma+in+the+mouse+results+in+acute+cognitive+deficits+and+sustained+impairment+of+axonal+function.">Concussive brain trauma in the mouse results in acute cognitive deficits and sustained impairment of axonal function.</a> J Neurotrauma. 28 (4), 547-563 (2011).</li><li>Hamberger, 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=Concussion+in+professional+football:+morphology+of+brain+injuries+in+the+NFL+concussion+model--part+16.">Concussion in professional football: morphology of brain injuries in the NFL concussion model--part 16.</a> Neurosurgery. 64 (6), 1174-1182 (2009).</li><li>Kane, M. 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=A+mouse+model+of+human+repetitive+mild+traumatic+brain+injury.">A mouse model of human repetitive mild traumatic brain injury.</a> J Neurosci Methods. 203 (1), 41-49 (2012).</li><li>Prins, M. 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=Repeat+traumatic+brain+injury+in+the+juvenile+rat+is+associated+with+increased+axonal+injury+and+cognitive+impairments.">Repeat traumatic brain injury in the juvenile rat is associated with increased axonal injury and cognitive impairments.</a> Dev Neurosci. 32 (5-6), 510-518 (2010).</li><li>Tang, Y. P., 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=A+concussive-like+brain+injury+model+in+mice+(II):+selective+neuronal+loss+in+the+cortex+and+hippocampus.">A concussive-like brain injury model in mice (II): selective neuronal loss in the cortex and hippocampus.</a> J Neurotrauma. 14 (11), 863-873 (1997).</li><li>Winston, C. N., 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=Dendritic+Spine+Loss+and+Chronic+White+Matter+Inflammation+in+a+Mouse+Model+of+Highly+Repetitive+Head+Trauma.">Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma.</a> Am J Pathol. 186 (3), 552-567 (2016).</li><li>Johnson, V. E., 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=Inflammation+and+white+matter+degeneration+persist+for+years+after+a+single+traumatic+brain+injury.">Inflammation and white matter degeneration persist for years after a single traumatic brain injury.</a> Brain. 136, 28-42 (2013).</li><li>Barrio, J. 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=In+vivo+characterization+of+chronic+traumatic+encephalopathy+using+[F-18]FDDNP+PET+brain+imaging.">In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.</a> Proc Natl Acad Sci U S A. 112 (16), 2039-2047 (2015).</li></ol>

著者は何も開示することはない。

ヒトにおいて、mTBIは、構造的損傷がない場合の機能障害によって特徴付けられる。これは、意識消失の有無にかかわらず発生する可能性がある1 。脳震盪を繰り返す暴露は、現在、CTE 4などの神経変性疾患の発症および/または進行の根底にあると考えられている。 CTEは一般的にボクサーやフットボールの選手には見られますが、反復脳震盪（意識消失をも...

外傷性脳傷害（TBI）は、外部の物理的な力から持続される頭部外傷として定義され、正常な脳機能の破壊をもたらす。これは、疾病予防予防センター（The Disease Control and Prevention Center）2015年の報告書によると、毎年250万人のアメリカ人が毎年TBIを維持していると推定して、社会経済的および公衆衛生上の重大な負担となっています。これは、患者の生活の質に影響を与えるだけでなく、現在、年間765億ドルと推定される、コミュニティに非常に高い経済的費用をかける。実際の脳損傷の量および急性期の症状は、軽度、中等度および重度のTBIを定義するものである。 脳震盪とも呼ばれる軽度の外傷性脳傷害（mTBI）は、毎年報告されているTBIの70％以上を占めています1 。ボクシングやサッカーを含むハイリスクの接触スポーツに参加する選手の間で最も一般的です。中等度とは異なりまたは重度のTBIの場合、mTBIに伴う即時の傷害および症状は時には顕著ではない3 。対照的に、mTBIの長期的な効果は、中等度および重度の形態で見られるものと同様に衰弱させることができます。反復性mTBIに苦しむ人々は、慢性的な外傷性脳症（CTE）ならびに他の認知および変性疾患を発症することが示されている4 。したがって、mTBI後に起こる短期症状や全体的な長期的な損傷に寄与するメカニズムをより深く理解することが重要です。 人間の場合、スポーツにおける脳震盪に関する第4回国際会議（チューリッヒ2012） 5で定義された脳震盪の定義は、スポーツ脳震盪の軽度のレベルは軽度であり、肉眼的病理学的変化を引き起こさないが、短期間の神経学的欠損自発的に解決されます。実際、受信者nt研究は、頭部衝撃遠隔測定システムを用いて、高校サッカー選手における認知障害に対するmTBIの効果を調べた。この調査では、1シーズンで20グラムを超えるヘルメットインパクトをプレイヤーが持続した回数が、最低226（平均4.7セッション）から最高1855（平均38.6 /セッション6 ）の範囲であった6 。これらの影響の大部分は、脳震盪の臨床診断をもたらさなかった。 fMRI 6を用いて脳機能の機能的変化の証拠を観察することができた。これらの機能的変化を引き起こす脳の変化は未知であり、したがって、脳震盪および副作用のあるmTBIの効果の研究を容易にするための信頼性の高い再現性のあるモデルが求められています。 マウスおよびラットでmTBIをモデル化する以前の試みにもかかわらず、多くの場合、有害作用が報告されている。特に、ほとんどのげっ歯類モデルは、より少ないthを用いてその反復性が制限されている頭蓋内出血、頭蓋骨折、重症の軸索損傷、神経細胞死、死亡率の増加などの有害な病理学的事象を有することが示されている8,9,10,11,12。ここでは、人間の脳震盪の真の定義に近いmTBIのマウスモデルについて説明する。このモデルは、ヒトのmTBIで観察される症状の多くを再現します。例えば、顕性肉眼的脳病変がなく、意識の一過性喪失をもたらす機械的力です。さらに、これまでに報告されているように、長時間にわたって単一衝撃および反復衝撃パラダイムの両方に利用できるという利点がある。

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			<td height="21" style="height:21px;width:323px;">Powerlab 8SP data acquisition (DAQ) control box&#160;</td>
			<td style="width:203px;">(AD instruments)</td>
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			<td style="width:167px;"></td>
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			<td height="21" style="height:21px;width:323px;">VIP 3000 calibrated vaporizer</td>
			<td style="width:203px;">Matrx</td>
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			<td height="21" style="height:21px;">Isoflurane</td>
			<td style="width:203px;">Henry Schein Animal Health</td>
			<td style="width:119px;">29405</td>
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			<td height="21" style="height:21px;width:323px;">Oxygen</td>
			<td style="width:203px;"></td>
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			<td>Commercially available</td>
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			<td height="21" style="height:21px;width:323px;">Compressed Air</td>
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			<td>Commercially available</td>
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			<td height="21" style="height:21px;">Masking Tape</td>
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			<td style="width:119px;"></td>
			<td>Commercially available</td>
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			<td height="21" style="height:21px;">Stop Watch</td>
			<td style="width:203px;">Fisher Scientific</td>
			<td>02-261-840</td>
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			<td height="21" style="height:21px;">C57 Bl/6 Mice</td>
			<td style="width:203px;">Jackson Laboratories</td>
			<td style="width:119px;"></td>
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			<td height="21" style="height:21px;width:323px;">Digital Scale and weigh container</td>
			<td style="width:203px;">Fisher Scientific</td>
			<td>20031</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:323px;">anti-Iba1 antibody</td>
			<td style="width:203px;">Wako</td>
			<td style="width:119px;">019-19741</td>
			<td></td>
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			<td height="21" style="height:21px;width:323px;">HRP labelled secondary&#160;</td>
			<td style="width:203px;">Jackson Immunoresearch</td>
			<td style="width:119px;">111-035-003</td>
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a mouse model of single and repetitive mild traumatic brain injury

軽度の外傷性脳傷害（mTBI）は、混乱期、意識消失（LOC）、局所神経学的障害および記憶喪失を含む脳機能の急激な喪失をもたらし得る。接触スポーツに参加している選手は、多数のmTBIに曝される危険性が高い。スポーツ競技者の怪我のレベルでは、mTBIは肉眼的病理学的変化を引き起こさない軽度の傷害として定義されるが、自発的に解決される短期間の神経学的欠損を引き起こす。マウスおよびラットにおいてmTBIをモデル化するこれまでの試みにもかかわらず、多くの者が、頭蓋骨骨折、大脳内出血、軸索損傷および神経細胞死を含む総有害作用を報告している。本明細書では、臨床的に関連する症状を再現するmTBIの再現性の高い動物モデルを記載する。このモデルでは、カスタムメイド製の空気式衝撃装置を使用して閉鎖頭部外傷を提供しています。この衝撃は、正確な速度および変形パラメータの下で行われ、単一または反復的な脳卒中mTBIの効果に寄与するメカニズムを調べるための信頼性の高い再現性のあるモデルを作成します。

この新しいmTBIデバイスの使用は、頭蓋骨の骨折または構造的な脳損傷のリスクを伴わずに、軽度の頭部損傷を1回および反復することを可能にする。このモデルでは、カスタムメイドの空気式テフロン・インパクター・デバイスを使用して、閉じた頭部の機械的エネルギーの影響を与えます。この衝撃は、正確な速度と変形のパラメータの下で行われ、信頼性の高い?...

Watch this Scientific Journal Video about A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury at JoVE.com

A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

アスリートは毎年数百の軽度の外傷性脳傷害（mTBI）/脳震盪を吸収する。しかし、これらの脳への帰結はあまり理解されていません。したがって、臨床的に関連する症状を一貫して複製する単一および反復mTBIの動物モデルは、mTBIおよび脳震盪の研究を進める手段を提供する。

片性および反復性軽度外傷性脳損傷のマウスモデル

Mild Traumatic Brain Injury (mTBI) can result in the acute loss of brain function, including a period of confusion, a loss of consciousness (LOC), focal ...

a-mouse-model-of-single-and-repetitive-mild-traumatic-brain-injury

Research

JoVE Journal

Medicine

11.0K ビュー.  Georgetown University Medical Center. アスリートは毎年数百の軽度の外傷性脳傷害（mTBI）/脳震盪を吸収する。しかし、これらの脳への帰結はあまり理解されていません。したがって、臨床的に関連する症状を一貫して複製する単一および反復mTBIの動物モデルは、mTBIおよび脳震盪の研究を進める手段を提供する。 

ビデオ: A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

Normothermic Cardiac Arrest and Cardiopulmonary Resuscitation: A Mouse Model of Ischemia-Reperfusion Injury

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused by whole-body hypoperfusion.5,6 Successful reproduction of whole-body hypoperfusion in rodent models has been fraught with 
difficulty.7-9,9,10 Models which employ focal ischemia have repeatedly demonstrated results which do not translate to the clinical setting, and larger 
animal models which allow for whole body hypoperfusion lack access to the full toolset of genetic manipulation possible in the mouse.11,12 However, in recent 
years a mouse model of cardiac arrest and cardiopulmonary resuscitation has emerged which can be adapted to model AKI.13 This model reliably reproduces 
physiologic, functional, anatomic, and histologic outcomes seen in clinical AKI, is rapidly repeatable, and offers all of the significant advantages of a murine surgical 
model, including access to genetic manipulative techniques, low cost relative to large animals, and ease of use. Our group has developed extensive experience 
with use of this model to assess a number of organ-specific outcomes in AKI.14,15

A powerful model for perioperative and critical care related acute kidney injury is presented. Using whole body hypoperfusion induced by cardiac arrest it is possible to nearly replicate the histologic and functional changes of clinical AKI.

正常体温心停止と心肺蘇生法：虚血再灌流障害のマウスモデル

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused ...

医学

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for objective diagnosis but also for the evaluation of therapeutic efficacy and resilience to trauma. Ongoing research is directed at identifying molecular biomarkers for PTSD, including traumatic stress induced proteins, transcriptomes, genomic variances and genetic modulators, using biologic samples from subjects' blood, saliva, urine, and postmortem brain tissues. However, the correlation of these biomarker molecules in peripheral or postmortem samples to altered brain functions associated with psychiatric symptoms in PTSD remains unresolved. Here, we present an animal model of PTSD in which both peripheral blood and central brain biomarkers, as well as behavioral phenotype, can be collected and measured, thus providing the needed correlation of the central biomarkers of PTSD, which are mechanistic and pathognomonic but cannot be collected from people, with the peripheral biomarkers and behavioral phenotypes, which can.
Our animal model of PTSD employs restraint and tail shocks repeated for three continuous days - the inescapable tail-shock model (ITS) in rats. This ITS model mimics the pathophysiology of PTSD 17, 7, 4, 10. We and others have verified that the ITS model induces behavioral and neurobiological alterations similar to those found in PTSD subjects 17, 7, 10, 9. Specifically, these stressed rats exhibit (1) a delayed and exaggerated startle response appearing several days after stressor cessation, which given the compressed time scale of the rat's life compared to a humans, corresponds to the one to three months delay of symptoms in PTSD patients (DSM-IV-TR PTSD Criterian D/E 13), (2) enhanced plasma corticosterone (CORT) for several days, indicating compromise of the hypothalamopituitary axis (HPA), and (3) retarded body weight gain after stressor cessation, indicating dysfunction of metabolic regulation.
The experimental paradigms employed for this model are: (1) a learned helplessness paradigm in the rat assayed by measurement of acoustic startle response (ASR) and a charting of body mass; (2) microdissection of the rat brain into regions and nuclei; (3) enzyme-linked immunosorbent assay (ELISA) for blood levels of CORT; (4) a gene expression microarray plus related bioinformatics tools 18. This microarray, dubbed rMNChip, focuses on mitochondrial and mitochondria-related nuclear genes in the rat so as to specifically address the neuronal bioenergetics hypothesized to be involved in PTSD.

We describe a rat model of post traumatic stress disorder (PTSD) that reveals the persistent alterations in neuroendocrine function and the delayed long-term, exaggerated fear response, characteristic of PTSD patients. The animal model and methods described here are useful for correlating biomarkers in brain nuclei, which are mechanistic but cannot be measured in patients, with biomarkers in peripheral white blood cells, which can.

PTSDの、ニューラル血液学的および行動的相関関係を明らかにするための動物モデルにおけるバイオマーカー

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for ...

Stretch in Brain Microvascular Endothelial Cells (cEND) as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying mechanisms involved in it are useful for treatment. There are both in vivo and in vitro methods available for this purpose. In vivo models can mimic actual head injury as it occurs during TBI. However, in vivo techniques may not be exploited for studies at the cell physiology level. Hence, in vitro methods are more advantageous for this purpose since they provide easier access to the cells and the extracellular environment for manipulation.
Our protocol presents an in vitro model of TBI using stretch injury in brain microvascular endothelial cells. It utilizes pressure applied to the cells cultured in flexible-bottomed wells. The pressure applied may easily be controlled and can produce injury that ranges from low to severe. The murine brain microvascular endothelial cells (cEND) generated in our laboratory is a well-suited model for the blood brain barrier (BBB) thus providing an advantage to other systems that employ a similar technique. In addition, due to the simplicity of the method, experimental set-ups are easily duplicated. Thus, this model can be used in studying the cellular and molecular mechanisms involved in TBI at the BBB.

Stretch in Brain Microvascular Endothelial Cells cEND as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

In vitro traumatic brain injury models are being developed to reproduce in vivo brain deformation. Stretch-induced injury has been employed for astrocytes, neurons, glial cells, aortic, and brain endothelial cells. However, our system uses a blood brain barrier (BBB) model that possesses properties constituting a legitimate model of the BBB to establish an in vitro&#160;TBI model.

として脳微小血管内皮細胞（CEND）でストレッチ<em&gt;インビトロ</em血液脳関門の&gt;外傷性脳損傷モデル

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying ...

An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse

Under normal conditions, the cornea is avascular, and this transparency is essential for maintaining good visual acuity. Neovascularization (NV) of the cornea, which can be caused by trauma, keratoplasty or infectious disease, breaks down the so called &lsquo;angiogenic privilege' of the cornea and forms the basis of multiple visual pathologies that may even lead to blindness. Although there are several treatment options available, the fundamental medical need presented by corneal neovascular pathologies remains unmet. In order to develop safe, effective, and targeted therapies, a reliable model of corneal NV and pharmacological intervention is required. Here, we describe an alkali-burn injury corneal neovascularization model in the mouse. This protocol provides a method for the application of a controlled alkali-burn injury to the cornea, administration of a pharmacological compound of interest, and visualization of the result. This method could prove instrumental for studying the mechanisms and opportunities for intervention in corneal NV and other neovascular disorders.

Neovascularization (NV) of the cornea can complicate multiple visual pathologies. Utilizing a controlled, alkali-burn injury model, a quantifiable level of corneal NV can be produced for mechanistic study of corneal NV and evaluation of potential therapies for neovascular disorders.

マウス角膜血管新生のアルカリ熱傷損傷モデル

Under normal conditions, the cornea is avascular, and this transparency is essential for maintaining good visual acuity. Neovascularization (NV) of the ...

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, ...

Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration

Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in patients and occlusion of renal blood flow is unavoidable during renal transplantation. Experimental models that accurately and reproducibly recapitulate renal IRI are crucial in dissecting the pathophysiology of AKI and the development of novel therapeutic agents. Presented here is a mouse model of renal IRI that results in reproducible AKI. This is achieved by a midline laparotomy approach for the surgery with one incision allowing both a right nephrectomy that provides control tissue and clamping of the left renal pedicle to induce ischaemia of the left kidney. By careful monitoring of the clamp position and body temperature during the period of ischaemia this model achieves reproducible functional and structural injury. Mice sacrificed 24 hr&#160;following surgery demonstrate loss of renal function with elevation of the serum or plasma creatinine level as well as structural kidney damage with acute tubular necrosis evident. Renal function improves and the acute tissue injury resolves during the course of 7 days following renal IRI such that this model may be used to study renal regeneration. This model of renal IRI has been utilized to study the molecular and cellular pathophysiology of AKI as well as analysis of the subsequent renal regeneration.

The mouse model of renal ischaemia reperfusion injury described here comprises of a right nephrectomy that provides control tissue and clamping of the left renal pedicle to induce ischaemia that results in acute kidney injury. This model uses a midline laparotomy approach with all steps performed via one incision.

腎臓虚血再灌流障害：障害のマウスモデルおよび再生

Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in patients and occlusion of renal blood flow is unavoidable ...

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls, a reliable animal model of mTBI had previously not been developed for this important aspect of development. The modified weight-drop technique employs a glancing impact to the head of a freely moving rodent transmitting acceleration, deceleration, and rotational forces upon the brain. When applied to juvenile rats, this modified weight-drop technique induced clinically relevant behavioural outcomes that were representative of post-concussion symptomology. The technique is a rapidly applied procedure with an extremely low mortality rate, rendering it ideal for high-throughput studies of therapeutics. In addition, because the procedure involves a mild injury to a closed head, it can easily be used for studies of repetitive brain injury. Owing to the simplistic nature of this technique, and the clinically relevant biomechanics of the injury pathophysiology, the modified weight-drop technique provides researchers with a reliable model of mTBI that can be used in a wide variety of behavioural, molecular, and genetic studies.

The modified weight-drop technique is an easy, cost-effective procedure used for the induction of mild traumatic brain injury in juvenile rats. This novel technique produces clinically relevant symptomology that will advance the study of mild traumatic brain injury (mTBI) and concussion.

少年ラット用マイルド外傷性脳損傷の新規モデル

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor ...

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 ...

A Repetitive Concussive Head Injury Model in Mice

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of knowledge on the injury and its effects. To develop a better understanding of concussions, animals are often used because they provide a controlled, rigorous, and efficient model. Studies have adapted traditional animal models to perform mTBI to stimulate mild injury severity by changing the injury parameters. These models have been used because they can produce morphologically similar brain injuries to the clinical condition and provide a spectrum of injury severities. However, they are limited in their ability to present the identical features of injuries in patients. Using a traditional impact system, a repetitive concussive injury (rCHI) model can induce mild to moderate human-like concussion. The injury degree can be determined by measuring the period of loss of consciousness (LOC) with a sign of a transient termination of breathing. The rCHI model is beneficial to use for its accuracy and simplicity in determining mTBI effects and potential treatments.

Concussion presents the most common type of traumatic brain injury. Therefore, a repetitive concussive animal model, which replicates the important features of an injury in patients, may provide a means to study concussion in a rigorous, controlled, and efficient manner.

マウスにおける反復震とう頭部損傷モデル

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of ...

A Tissue Displacement-based Contusive Spinal Cord Injury Model in Mice

Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between experimental animals. Several contusive SCI models have been developed to produce injuries using different mechanisms. The severity of the SCI is based on the height that a given weight is dropped, the injury force, or the spinal cord displacement. In the current study, we introduce a novel mouse contusive SCI device, the Louisville Injury System Apparatus (LISA) impactor, which can create a displacement-based SCI with high injury velocity and accuracy. This system utilizes laser distance sensors combined with advanced software to produce graded and highly-reproducible injuries. We performed a contusive SCI at the 10th thoracic vertebral (T10) level in mice to demonstrate the step-by-step procedure. The model can also be applied to the cervical and lumbar spinal levels.

We introduce a tissue displacement-based contusive spinal cord injury model that can produce a consistent contusive spinal cord injury in adult mice.

マウスにおける組織変位ベースの脊柱挫傷モデルの検討

Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between ...