Name: controlled cortical impact model for traumatic brain injury
Uploaded: 2014-08-05T16:00:00.000+00:00
Duration: 5 min 30 s
Description: Watch this Scientific Journal Video about Controlled Cortical Impact Model for Traumatic Brain Injury at JoVE.com

この作品は、インディアナ州脊髄·脳損傷研究費補助金（SCBI 200-12）からの資金によってラルフ·W·グレースM·ショーウォルター研究賞、インディアナ大学の生物学的研究助成、NIHの助成金RR025761と1R21NS072631-01Aをサポートされていました。

動物ケア 雄のC57 BL / 6マウスを基に収容された食物および水を自由にアクセスでき、無料で12分の12時間の明/暗サイクルで維持した。このプロトコルで使用される動物は、10〜12週齢であった。すべての手順は、インディアナ大学の動物実験委員会によって承認されたプロトコルの下で実施された。 1。手術の準備<ol><li>ケタミン/キシラジン混合物（87.7 mg / mlのケタミンおよび12.3 mg / mlのキシラジン）を使用して、マウスを麻酔し、IP注射を介して（1ミリリットル/ kg）を管理します。 </li><li>耳の間にマウスの頭を剃る。 </li><li>手術中に乾燥を防ぐために、マウスの目に石油系ゼリーを適用します。 </li><li> 10％のヨウ素とパイパンエリアを清掃してください。その後、ヨウ素をきれいに70％エタノールを使用しています。 </li><li>耳のバーやバイトプレートを使用し、定位フレームにマウスの頭を固定します。脳が安定していることを確認してください。 </li></ol> 2。頭蓋骨切除術</P&gt; <ol><li>はさみで頭の真ん中に縦切開を加えます。左側に皮を保持するために止血剤を使用しています。 </li><li>頭蓋骨を露出するために骨に血液や組織を除去するために綿棒を使用してください。さらさ頭蓋骨は1分間乾燥させます。 </li><li>圧力をかけると、頭蓋骨は不動のままであることを確実にするために鉗子を使用してください。解剖学的ラムダ（尾の態様）とブレグマ（前頭面）を特定します。直径4mmと離れて正中線から0.5ミリメートルでラムダとブレグマの中心に円を描く。 </li><li>マークされた円に沿ってカットしてドリルを使用してください。そっと骨ほこりを吹き飛ばす。硬膜の損傷を防ぐために骨を完全に貫通してドリルダウンしないでください。 </li><li>骨を除去し、硬膜を露出させ鉗子を使用してください。 </li></ol> 3。インパク衝撃装置は、衝撃パラメータを設定するコントロールボックス、インパクションを実行するためのアクチュエータと、行為を確保する定位フレームを含むインパクト用uatorとマウスの頭部。 <ol><li>手術前に3メートル/秒アクチュエータの速度を事前に設定してください。 </li><li>別の傷害の重大度を誘導するために様々な変形の深さを事前に設定してください。 0.0〜0.2ミリメートル0.5〜1.0 mmであり、1.2〜2.0ミリメートルの変形深さはそれぞれ、軽度、中等度、重度のTBiSをもたらすであろう。このプロトコルは、3メートル/秒の速度を利用して1ミリメートルの変形の深さが中等度の脳損傷を達成する方法を説明しました。 </li><li>定位フレームにホルダーにアクチュエータを取り付け、オープン頭蓋骨領域の中央にある丸い、アクチュエータのフラットチップ（直径3mm）を確保するためにそれを動かすマイクロマニピュレーターを使用しています。その後、衝突場所の表面に対して平行な角度で先端を調整します。 </li><li>先端が衝突部位の表面に接触するまで拡張モデルでアクチュエータを下に移動することでゼロ点を確立します。ゼロに定位コントロールパネルのZチャネルを設定します。 </li><li>インパクター先端を撤回同時に1ミリメートルまでのアクチュエータを移動させながら。 </li><li>損傷部位に衝突し、1ミリメートルの変形深さを達成するためにインパクトのボタンを押してください。 </li></ol> 4。傷害のサイト閉鎖<ol><li>任意の血液、次の影響を除去するために綿棒アプリケーターを使用していますが、怪我の部分に触れないでください。 </li><li>体温を維持するために、暖かいパッドの上にマウスを置きます。 </li><li>出血が停止すると、閉じた傷口を縫合。清潔なケージに戻って動物を入れて、それが暖かいパッド上で一晩手術から回復することができます。 </li><li>管理ブプレノルフィン0.05〜0.10 mg / kgのSQ手術後2日間、8月12日時間。 </li></ol>

<ol>
	<li>Menon, D. K., Schwab, K., 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=Position+statement:+definition+of+traumatic+brain+injury.">Position statement: definition of traumatic brain injury.</a> Arch Phys Med Rehabil. 91 (11), 1637-1640 (2010).</li><li>Lighthall, J. W., Dixon, C. 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=Experimental+models+of+brain+injury.">Experimental models of brain injury.</a> J Neurotrauma. 6 (2), 83-97 (1989).</li><li>Dixon, C. E., Clfton, G. 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=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 (3), 253-262 (1991).</li><li>Scheff, S. W., Baldwin, S. 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=Morris+water+maze+deficits+in+rats+following+traumatic+brain+injury:+lateral+controlled+cortical+impact.">Morris water maze deficits in rats following traumatic brain injury: lateral controlled cortical impact.</a> J Neurotrauma. 14 (9), 615-627 (1997).</li><li>Smith, D. H., Soares, H. 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=A+model+of+parasagittal+controlled+cortical+impact+in+the+mouse:+cognitive+and+histopathologic+effects.">A model of parasagittal controlled cortical impact in the mouse: cognitive and histopathologic effects.</a> J Neurotrauma. 12 (2), 169-178 (1995).</li><li>Hannay, H. J., Feldman, Z., 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=Validation+of+a+controlled+cortical+impact+model+of+head+injury+in+mice.">Validation of a controlled cortical impact model of head injury in mice.</a> J Neurotrauma. 16 (11), 1103-1114 (1999).</li><li>Natale, J. E., Ahmed, F., 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=Gene+expression+profile+changes+are+commonly+modulated+across+models+and+species+after+traumatic+brain+injury.">Gene expression profile changes are commonly modulated across models and species after traumatic brain injury.</a> J Neurotrauma. 20 (10), 907-927 (2003).</li><li>Anderson, R. W., Brown, C. 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=Impact+mechanics+and+axonal+injury+in+a+sheep+model.">Impact mechanics and axonal injury in a sheep model.</a> J Neurotrauma. 20 (10), 961-974 (2003).</li><li>Lighthall, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controlled+cortical+impact:+a+new+experimental+brain+injury+model.">Controlled cortical impact: a new experimental brain injury model.</a> J Neurotrauma. 5 (1), 1-15 (1988).</li><li>Chen, S., Pickard, J. 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=Time+course+of+cellular+pathology+after+controlled+cortical+impact+injury.">Time course of cellular pathology after controlled cortical impact injury.</a> Exp Neurol. 182 (1), 87-102 (2003).</li><li>Long, J. B., Bentley, T. 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=Blast+overpressure+in+rats:+recreating+a+battlefield+injury+in+the+laboratory.">Blast overpressure in rats: recreating a battlefield injury in the laboratory.</a> J Neurotrauma. 26 (6), 827-840 (2009).</li><li>Clark, R. S., Schiding, J. K., 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=Neutrophil+accumulation+after+traumatic+brain+injury+in+rats:+comparison+of+weight+drop+and+controlled+cortical+impact+models.">Neutrophil accumulation after traumatic brain injury in rats: comparison of weight drop and controlled cortical impact models.</a> J Neurotrauma. 11 (5), 499-506 (1994).</li><li>Werner, C., Engelhard, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathophysiology+of+traumatic+brain+injury.">Pathophysiology of traumatic brain injury.</a> Br J Anaesth. 99 (1), 4-9 (2007).</li><li>Colicos, M. A., Dixon, C. 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=Delayed,+selective+neuronal+death+following+experimental+cortical+impact+injury+in+rats:+possible+role+in+memory+deficits.">Delayed, selective neuronal death following experimental cortical impact injury in rats: possible role in memory deficits.</a> Brain Res. 739 (1-2), 111-119 (1996).</li><li>Raghavendra Rao, V. L., Dogan, 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=Traumatic+brain+injury+leads+to+increased+expression+of+peripheral-type+benzodiazepine+receptors,+neuronal+death,+and+activation+of+astrocytes+and+microglia+in+rat+thalamus.">Traumatic brain injury leads to increased expression of peripheral-type benzodiazepine receptors, neuronal death, and activation of astrocytes and microglia in rat thalamus.</a> Exp Neurol. 161 (1), 102-114 (2000).</li><li>Gao, X., Chen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Moderate+traumatic+brain+injury+promotes+neural+precursor+proliferation+without+increasing+neurogenesis+in+the+adult+hippocampus.">Moderate traumatic brain injury promotes neural precursor proliferation without increasing neurogenesis in the adult hippocampus.</a> Exp Neurol. 239, 38-48 (2013).</li></ol>

The authors have nothing to disclose.

成功したCCIを引き起こす電子の磁石の影響システムを使用して一貫性のあるのTBiSを発生させるための最も重要なステップは次のとおりです。1）安定的定位フレームにマウスの頭を固定。 2）マウスとの間の骨窓の同じサイズを生成し、頭蓋骨切除術の間に、その下の硬膜を損傷することなく骨を除去する工程; 3）が正しくオープンエリアの中心にインパクトチップを配置し、影響を与える前...

外傷性脳損傷（TBI）は、脳機能の変化、又は外力​​1によって引き起こされる脳病理の他の証拠として定義される。オーバフローなし、特に米国では、世界中で深刻な健康問題のまま。疾病管理予防センターによると、少なくとも170万のTBiSは、すべての傷害に関連した死亡の30.5％になり、米国で毎年起こる。 2000年には、直接医療費とのTBiSの間接的なコストは、米国だけで推定765億ドルとなりました。前の数十年の技術と治療の進歩がオーバフローなしで苦しむ人々の生活の質と長さを改善しているものの、有効な医薬品または予防治療は現在存在しません。により複雑さと組織病変、細胞死、および軸索変性を含むのTBiSの広い及ぶ影響​​で、どの2つの負傷者が同一ではありません。このように、動物には、現在のTBIのモデルを正確に再現していませんTBIのすべての側面は、ヒトにおいて見られる。しかし、動物モデルは、さらにのTBiSの臨床症状を理解するのを期待して、TBIの様々な影響を調査するために必要なほとんど同一の傷害を生成する能力を提供します。 制御皮質衝撃（CCI）モデルでは、動物の露出硬膜に物理的な衝撃を配信するためにインパクト方式を使用しています。これは、軽度から人間が経験と同様の深刻なまでのTBiSを誘導する。この損傷は、第2のフェレットを特徴とし、それ以降3,4ラット、マウス5-7、およびヒツジ8で使用するために適合させた。最初に特性化するので、損傷部位は正中線2,9と横皮質10上の両方に置かれています。 CCIはオーバフローなしのための効果や治療の可能性を調査する簡単かつ正確な方法を提供します。 CCIモデルに加えて、流体打楽器および体重降下モデルは同時であるmmonlyのTBiSを生成するために使用される。しかし、これらのモデルより少ない傷害パラメータを制御、人間のTBiSでは見られないhistopathalogical変化をもたらす、マウス3,5,10中の事故死の高い発生率を含めて、本制限は、。爆風モデルものTBiSを生成するために使用される。爆風モデルは機械的衝撃後に見histopathalogical変化を再現していませんが、このモデルは、正確に、特に軍関係者11が経験したのTBiSを生み出すん。制御皮質衝撃モデルは、インパクト5時、速度、深さなどの変形パラメータを正確に制御するため、制御が容易である。このような精度はより実現可能動物のグループ全体でほぼ同一の傷害を複製することができます。最も重要なことは、CCIは、人間のTBiS 12に見られるような機能を持つのTBiSを再生する。しかし、病理学ちゃんの完全なスペクトルを再現する完全に成功している単一の動物モデルは存在しないTBIの後に観察GES。さらなる研究は、完全TBI後に生じる急性および慢性の変化を明らかにすることが必要である。 プライマリとセカンダリの負傷：負傷の2つのタイプがTBI後に発生する。主な損傷はインパクトの瞬間に発生し、治療上の処置に敏感ではありません。しかし、最初の損傷後も持続二次傷害は治療13の対象となります。制御皮質衝撃モデルは、このように研究者が二次的傷害の可能性のある長期的な効果のためのTBIと潜在的な治療処置の効果を調査することができ、主要な傷害を生成します。 CCIモデルを使用して潜在的な研究の分野は、神経細胞死、脳浮腫、神経発生、血管作用、histopathalogical変化、記憶障害や3,13-16などが含まれます。

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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.

制御皮質衝撃モデルは、軽度から重度までの重症度の範囲のTBiSを生成します。ポストインパクトインパクトサイトで頭蓋膨潤量、出血および頭蓋の歪み速度と変形深さのパラメータに起因する傷害の重症度を明らかにする。軽度のTBiSは、限定された硬膜の侵害に衝突場所と、わずかな出血で頭蓋腫れを引き起こす。適度なTBIは頭蓋腫脹を示し、原因衝突時に硬膜違反（ 図1）に?...

Watch this Scientific Journal Video about Controlled Cortical Impact Model for Traumatic Brain Injury at JoVE.com

Controlled Cortical Impact Model for Traumatic Brain Injury

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, ...

controlled-cortical-impact-model-for-traumatic-brain-injury

Research

JoVE Journal

Medicine

28.5K ビュー.  Indiana University School of Medicine. 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.

ビデオ: Controlled Cortical Impact Model for Traumatic Brain Injury

Controlled Cortical Impact Model of Mouse Brain Injury with Therapeutic Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Cells

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. Disease pathology due to TBI progresses from the primary mechanical insult to secondary injury processes, including apoptosis and inflammation. Animal modeling has been valuable in the search to unravel injury mechanisms and evaluate potential neuroprotective therapies. This protocol describes the controlled cortical impact (CCI) model of focal, open-head TBI. Specifically, parameters for producing a mild unilateral cortical injury are described. Behavioral consequences of CCI are analyzed using the adhesive tape removal test of bilateral sensorimotor integration. Regarding experimental therapy for TBI pathology, this protocol also illustrates a process for transplanting cultured cells into the brain. Neural cell cultures derived from human induced pluripotent stem cells (hiPSCs) were chosen for their potential to show superior functional restoration in human TBI patients. Chronic survival of hiPSCs in the host mouse brain tissue is detected using a modified DAB immunohistochemical process.

This protocol demonstrates methodologies for a mouse model of open-skull traumatic brain injury and transplantation of cultured human induced pluripotent stem cell-derived cells into the injury site. Behavioral and histologic tests of outcomes from these procedures are also described in brief.

ヒト誘導多能性幹細胞由来神経細胞の治療移植によるマウス脳損傷の制御された皮質衝撃モデル

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. Disease pathology due to TBI progresses from the primary mechanical ...

発生生物学

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 ...

医学

A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

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 neurological deficits and even amnesia. Athletes participating in contact sports are at high risk of exposure to large number of mTBIs. In terms of the level of injury in a sporting athlete, a mTBI is defined as a mild injury that does not cause gross pathological changes, but does cause short-term neurological deficits that are spontaneously resolved. Despite previous attempts to model mTBI in mice and rats, many have reported gross adverse effects including skull fractures, intracerebral bleeding, axonal injury and neuronal cell death. Herein, we describe our highly reproducible animal model of mTBI that reproduces clinically relevant symptoms. This model uses a custom made pneumatic impactor device to deliver a closed-head trauma. This impact is made under precise velocity and deformation parameters, creating a reliable and reproducible model to examine the mechanisms that contribute to effects of single or repetitive concussive mTBI.

Athletes absorb several hundred mild traumatic brain injuries (mTBI)/concussions every year; however, the consequence of these on the brain is poorly understood. Therefore, an animal model of single and repetitive mTBI that consistently replicates clinically relevant symptoms provides the means to advance the study of mTBI and concussion.

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 ...

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 ...

神経科学

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 ...

A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the pathophysiological mechanism and to develop effective therapeutic strategy for this devastating neurological disorder. Intraparenchymal hemorrhage and post-traumatic inflammatory response induced by initial physical impact can aggravate microglia/macrophage activation and neuroinflammation which subsequently worsen brain pathology. We provide here a controlled cortical impact (CCI) protocol that can reproduce experimental cortical contusion in mice by using a pneumatic impactor system to deliver mechanical force with controllable magnitude and velocity onto the dural surface. This preclinical model allows researchers to induce moderately severe focal cerebral contusion in mice and to investigate a wide range of post-traumatic pathological progressions including hemorrhage contusion, microglia/macrophage activation, iron toxicity, axonal injury, as well as short-term and long-term neurobehavioral deficits. The present protocol can be useful for exploring the long-term effects of and potential interventions for cerebral contusion.

<meta charset="utf8"></head><body>外傷性出血挫傷および神経炎症に対する前臨床制御皮質衝撃モデル

Intraparenchymal hemorrhage and neuroinflammation accompanied by cerebral contusion can trigger severe secondary brain injury. This protocol details a mouse controlled cortical impact (CCI) model allowing researchers to study hemorrhage contusion and post-traumatic immune responses and explore potential therapeutics.

外傷性出血挫傷および神経炎症に対する前臨床制御皮質衝撃モデル

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the ...

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 ...

Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of closed-head mTBI in the preclinical setting to increase translatability to the clinical population. The awake closed-headed injury (ACHI) model uses a modified controlled cortical impactor to deliver closed-headed injury, inducing clinically relevant behavioral deficits without the need for a craniotomy or the use of an anesthetic.
This technique does not normally induce fatalities, skull fractures, or brain bleeds, and is more consistent with being a mild injury. Indeed, the mild nature of the ACHI procedure makes it ideal for studies investigating repetitive mTBI (r-mTBI). Growing evidence indicates that r-mTBI can result in a cumulative injury that produces behavioral symptoms, neuropathological changes, and neurodegeneration. r-mTBI is common in youths playing sports, and these injuries occur during a period of robust synaptic reorganization and myelination, making the younger population particularly vulnerable to the long-term influences of r-mTBI.
Further, r-mTBI occurs in cases of intimate partner violence, a condition for which there are few objective screening measures. In these experiments, synaptic function was assessed in the hippocampus in juvenile rats that had experienced r-mTBI using the ACHI model. Following the injuries, a tissue slicer was utilized to make hippocampal slices to evaluate bidirectional synaptic plasticity in the hippocampus at either 1 or 7 days following the r-mTBI. Overall, the ACHI model provides researchers with an ecologically valid model to study changes in synaptic plasticity following mTBI and r-mTBI.

Here, it is demonstrated how an awake closed-head injury model can be used for examining the effects of repeated mild traumatic brain injury (r-mTBI) on synaptic plasticity in the hippocampus. The model replicates important features of r-mTBI in patients and is used in conjunction with in vitro electrophysiology.

軽度外傷性脳損傷の覚醒閉鎖頭部損傷モデルを用いたシナプス可塑性変化の評価

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of ...

クローズドヘッドケガ法によるマウスのrmTBI導入

Modified Mouse Model of Repetitive Mild Traumatic Brain Injury Incorporating Thinned-Skull Window and Fluid Percussion

Mild traumatic brain injury is a clinically highly heterogeneous neurological disorder. Highly reproducible traumatic brain injury (TBI) animal models with well-defined pathologies are urgently needed for studying the mechanisms of neuropathology after mild TBI and testing therapeutics. Replicating the entire sequelae of TBI in animal models has proven to be a challenge. Therefore, the availability of multiple animal models of TBI is necessary to account for the diverse aspects and severities seen in TBI patients. CHI is one of the most common methods for fabricating rodent models of rmTBI. However, this method is susceptible to many factors, including the impact method used, the thickness and shape of the skull bone, animal apnea, and the type of head support and immobilization utilized. The aim of this protocol is to demonstrate a combination of the thinned-skull window and fluid percussion injury (FPI) methods to produce a precise mouse model of CHI-associated rmTBI. The primary objective of this protocol is to minimize factors that could impact the accuracy and consistency of CHI and FPI modeling, including skull bone thickness, shape, and head support. By utilizing a thinned-skull window method, potential inflammation due to craniotomy and FPI is minimized, resulting in an improved mouse model that replicates the clinical features observed in patients with mild TBI. Results from behavior and histological analysis using hematoxylin and eosin (HE) staining suggest that rmTBI can lead to a cumulative injury that produces changes in both behavior and gross morphology of the brain. Overall, the modified CHI-associated rmTBI presents a useful tool for researchers to explore the underlying mechanisms that contribute to focal and diffuse pathophysiological changes in rmTBI.

著者スポットライト:軽度外傷性脳損傷の繰り返しにおけるメカニズムとリハビリテーションを調査するためのげっ歯類モデルの最適化

This protocol presents a modified mouse model of repetitive mild traumatic brain injury (rmTBI) induced via a closed-head injury (CHI) method. The approach features a thinned-skull window and fluid percussion to reduce the inflammation commonly caused by meninges exposure, along with improved reproducibility and accuracy in modeling rmTBI in rodents.

間伐頭蓋窓と流体パーカッションを組み込んだ反復性軽度外傷性脳損傷の改良マウスモデル

Mild traumatic brain injury is a clinically highly heterogeneous neurological disorder. Highly reproducible traumatic brain injury (TBI) animal models ...

外傷性脳損傷のための制御皮質衝撃モデル

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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

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

外傷性出血挫傷および神経炎症に対する前臨床制御皮質衝撃モデル

外傷性出血挫傷および神経炎症に対する前臨床制御皮質衝撃モデル

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

軽度外傷性脳損傷の覚醒閉鎖頭部損傷モデルを用いたシナプス可塑性変化の評価

間伐頭蓋窓と流体パーカッションを組み込んだ反復性軽度外傷性脳損傷の改良マウスモデル