Name: detecting behavioral deficits in rats after traumatic brain injury
Uploaded: 2018-01-30T12:30:00.000+00:00
Duration: 7 min 54 s
Description: Watch this Scientific Journal Video about Detecting Behavioral Deficits in Rats After Traumatic Brain Injury at JoVE.com

彼女の細心の編集のための手術準備科目、エリザベス ・ サムナーをイアン ・太字を感謝いたします。これらの研究は、橋渡しの外傷性脳損傷研究のための不機嫌なプロジェクトによって資金を供給チームの一員として完成しました。

<ol>
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P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Properties+of+parametric+photic+entrainment+of+circadian+rhythms+in+the+rat.">Properties of parametric photic entrainment of circadian rhythms in the rat.</a> Physiol Behav. 50, 1233-1239 (1991).</li><li>Ferguson, S. A., Maier, K. 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+review+of+seasonal/circannual+effects+of+laboratory+rodent+behavior.">A review of seasonal/circannual effects of laboratory rodent behavior.</a> Physiol Behav. 119, 130-136 (2003).</li><li>Fujimoto, S. T., Longhi, L., Saatman, K. E., 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=Motor+and+cognitive+function+evaluation+following+experimental+traumatic+brain+injury.">Motor and cognitive function evaluation following experimental traumatic brain injury.</a> Neurosci &amp; Biobehav Reviews. , (2004).</li><li>Gold, E. M., Su, D., Lopez-Velazquez, L., Haus, D. L., Perez, H., Lacuesta, G. A., Anderson, A. J., Cummings, B. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+assessment+of+long-term+deficits+in+rodent+models+of+traumatic+brain+injury.">Functional assessment of long-term deficits in rodent models of traumatic brain injury.</a> Regen. Med. 8 (4), 483-516 (2013).</li></ol>

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行動テストの任意の種類を行うときは、一致する重要です。この詳細には、微々 たるものが、動物の応答に大きな影響を与える多くの考慮事項が含まれます。見逃すことのできない重要なステップは、どんな実験の前に彼らの家/ケージハウジング状況に動物の馴化です。この準備には、行動の結果18を変更することができます動物の生理学的ストレス反応の影響が軽減されます。同様に、それはすべての動物を同じ方法で処理されるあらゆる努力が不可欠です。この一貫性は、住宅に前述のとおり、順化も順化訓練やテスト前に部屋の間の輸送と含まれています。この概念を誇張することはできません。ずさんな動物の取り扱いは任意の行動テスト19に悲惨です。同様に、あらゆる努力をする必要があります日の同じ時に動物をテストする暗いまたは光のサイクルの間にあるかどうか。一貫したテストを行う限り、ここで説明するテスト、光や暗い段階でテスト可能です。概日周期のさまざまな段階で行っている検査は、行動の結果18,20を変更する示されています。さらに、動物と同様に、ハンドラーは結果の精度を最大化するためにストレス フリー、穏やかな状態でなければなりません。
Neuroscore、特に偽陽性とネガが多い。偽陽性は、動物は処理およびテストに完全に慣れていないときに通常発生します。観察された応答は再帰とストレスや恐怖のうち反応から引き締め筋肉によらないので、動物が完全にリラックスして必要があります。緊張したハンドラー動物にストレスを送信することで結果に影響することができます。したがって、きつすぎるまたは余りに緩い、ラットを保持することができます両方問題となります。また、ハンドラーは神経質な場合これはラットの反応を混同できます。また、経験の浅いオブザーバーがラットの応答を誤解すること危険があります。良い訓練と実践の多くは、成功と、Neuroscore の一貫性に不可欠です。
一般に、これらのテストの主な関心事の大きな違いと時々 治療群間差は、不足しています。動物は、別のハンドラー、騒音、時刻と、潜在的に、季節21別様に反応できる、のであらゆる努力はすべての可能な交絡因子を減らすために行わなければなりません。
ここに示すビーム バランスとビーム徒歩タスクの結果は、これらのテストは、vestibulomotor 機能の欠損を検出する損傷後早期は役を示しています。これらの赤字は通常時1,14を解決します。このモデルで、受傷後 6 ヶ月で、傷害による赤字が解決されています。6 月時点の結果を示すナイーブ、偽、または傷つけられたラットに差がないです。ただし、すべてのラットされているリラックス ホーム檻の中で 6 ヶ月間、加齢と体重が増えます。したがって、彼らは、6 ヶ月間手術後 (または素朴な場合と同等) 再テストまで、本質的に古いと脂肪となっております、したがってグループだけでなく、彼らは彼らのベースライン 0 日と比較して実行しないでくださいすべての結果します。
もう一つの重要な考慮事項は、使用の動作テストが正しいテストです。たとえば、ここに採用テストは、特定の脳領域の関数を表すと考えられます。1 つの例は前庭系、バランスのために重要であります。皮質、視床、皮質ニューロン、荷-線条体、数名、大脳基底核を含む大脳皮質などの感覚運動機能に関与する脳の領域は、すべて vestibulomotor 調整に関与しています。したがって、ビーム バランスやはり徒歩で赤字はこれらの分野で潜在的な障害を示します。さらに、前頭前野と海馬は、学習と記憶関数は作業メモリの水迷路でテストに関与しています。正しいテストを選択した場合にも採用されているテストの限界を念頭に保たれなければなりません。たとえば、ここで説明したテストのどれも気分、抑うつ、不安、攻撃性、意思決定、または衝動性など社会的な相互作用などで赤字に敏感。繰り返しますが、評価される行動と脳領域の適切なテストを選択することが不可欠です。
行動データの解釈、分析は、慎重に接近する必要があります。それはので、その性質上、微妙な効果の原油の測定は、神経赤字の対策として行動の結果を使用して個別にテストの種類ごとの電力解析を含めるに勧めします。さらに、別のテスト統計解析の種類が必要です。たとえば、説明する Neuroscore とビーム バランス テスト、順序尺度を使用して動作を獲得する訓練を受けた観察者の解釈に依存します。これらの種類のデータが連続しないと正規分布ではない、だからノンパラ メトリック統計を使用するクラスカル-ウォリス検定などのセクション 6.1、6.2 に示すよう。または、ビーム徒歩とワーキング メモリ水迷路テストが連続データを作成し、正規分布、だからパラメトリック統計などを使用できる、一方通行 ANOVA または繰り返される措置二元セクション 6.3、6.4 に示すよう。
ここで示した行動のタスク時間の試練に立っているし、特にと組み合わせればラット、FPI モデル行動実験脳損傷のための他の多くの方法が存在するが、再現可能な結果を与えます。Neuroscore は、装置の最低実行短い評価です。反射と強度の他のテストは利用できる、横 pulsion タスク無動テスト、傾斜面のテスト、握力 (藤本らを参照してくださいなどの神経学的な評価に組み込むことが22金ら23). のビーム バランスはり徒歩タスクの説明が傷害の後 vestibulomotor 赤字の対策です。Vestibulomotor の調整は、総歩行障害の他の措置 Rotarod、回転棒が含まれます、フィールド活動を開く総行動の 1 つのメジャーと見なすことができます。、泳ぐ能力は、水迷路の中に泳ぐ速度測定も総運動協調性22,23の示します。ワーキング メモリ水迷路課題によるテストのこのセットを完了する両方参照 (トライアル 1 によって示される) 記憶障害を検出し、作業記憶の障害 (トライアル 2 または体験版 1 と体験版 2 の違いによって示されます)。認知機能の他の措置 8 腕放射状迷路、バーンズ迷路、新規オブジェクト認識テスト、水迷路のさまざまなバリエーションがあります。これらのバリエーションは、元のモリス水迷路、ラシュリー III 迷路 (また見なさい藤本ら22金ら23). この一連のテストができることが実証損傷後早期と様々 な角度でアウト傷害1後 12 ヶ月。
異なる系統、セックス、ラットの年齢とここでデモンストレーションされるタスクを使用ことができますさらに、ただし、宿泊施設が異なるサイズおよびより大きいもろさの場合に行われる必要があります。たとえば、古い、重いラット ビーム バランス課題や高齢者、虚弱なラットの広いビームを必要があります、必要があります水の遊泳時間の短い期間の迷路のことがあります。したがって、これらのテストの柔軟性のための部屋と仮説とさまざまな状況に対応する新しいテストの開発の可能性があります。

紹介した方法は TBI のラット実験モデルによる特定の脳領域の機能的障害を検出するために設計されています。4 つの異なる動作テストが表示されます。まず、neuroscore と呼ばれる短いの神経学的評価はいずれかは専門機器しますが、不要な行為を必要とせず実行できます。このテストでは、反射の赤字を検出します。第二に、ビーム バランス テストは、バランスを取る能力の赤字を検出します。このタスクは、順序尺度に基づくラットをスコアにハンドラーが必要ですし、ハンドラーのいくつかのトレーニングが必要です。ビーム バランス テストは狭いビームを必要とする、前庭系の赤字に敏感。3 番目のテストは、vestibulomotor 調整を評価します。このテストはビーム徒歩タスクと呼ばれ、ラットのいくつかの事前の訓練が必要ですが、この手順は、前の 2 つよりもより客観的にビームを走査する待機時間は主観的な採点に依存しない客観的に測定。この違いは、安全なボックスに到達する狭いビームを走査する時間は測定されるためです。・ ビーム歩行テストは、ビーム バランスだけでなく、エスケープ ボックスより長いビームを必要です。このテストは、モーターの調整とバランスの赤字を測定し、こうして小脳や運動関連脳領域への損傷に敏感であります。モリス水迷路 (MWM WM) のワーキング メモリーのバージョンは、主に海馬機能と前頭前皮質または執行機能との統合をテストします。示されているモリス水迷路のバージョンを参照メモリ1に赤字を検出する使用もできます。
これらのメソッドは、文献での老舗の実績に基づいて選ばれました。それぞれは、研究の多くの年にラットの複数系統と異なる所から多くの手に有効されています。ただし、過去には、受傷後は傷害は、「慢性」の時点が考慮された後 2 週間までを測定します。したがって、齧歯動物の TBI の慢性的な影響の研究のための行動のテクニックを確立する TBI を検出する感度を評価するために必要なこれらのよく知られているメソッドは損傷後長い時点で赤字を誘発しました。今、TBI のいくつかの齧歯動物モデル、FPI モデルは最も広く使用されているの一つです、この研究に適用されます。21950 年代に発表されたこのモデルと、それ以来、1,000 以上の論文は、ラット3FPI を採用しています。このタイプの傷害の病理は私たち4と他の人がよく記載されている5,6,7。簡単に言えば、海馬で神経細胞傷害がフッ素玉が損傷、すなわち24-48 h; 後短時間で染色を用いた線量に依存する示されています。総萎縮しキャビテーションは、内包と皮質の菲薄化を含む傷害6、7の後の 1 年間に報告されています。
脳機能の最も意味のある表現は、実験的脳損傷後の行動結果の措置を使用して評価されます。ただし、行動の結果を使用する FPI 実験の大半対策を行います、比較的早く通常傷害の後の 14 日に 1 から。メソッドを使用していくつかの行動の赤字は、傷害1後 12 ヶ月を検出できる、ここで示します。神経学的な機能、総 vestibulomotor 機能、細かい運動の調整後負傷日 (Pid) 1-3 と 3、6、12 ヶ月短い神経学的評価を用いた手術後に評価された (Neuroscore; シャラート8から変更)、ビーム バランス タスク、およびビーム徒歩タスク9,10,11。参照記憶および作業記憶は、モリス水迷路1,12,13のワーキング メモリーのバージョンを使用して評価されました。

<table><tbody><tr><td>Sprague-Dawley rats</td><td>Charles Rivers Laboratories&lt;br/&gt; 251 Ballardvale St&lt;br/&gt; Wilmington, MA 01887-1096&lt;br/&gt; Phone: 800-522-7287</td><td>CD-IGS rats, strain code 001</td><td>male, albino, 300-350g at arrival</td></tr><tr><td>&lt;strong&gt;Name&lt;/strong&gt;</td><td>&lt;strong&gt;Company&lt;/strong&gt;</td><td>&lt;strong&gt;Catalog Number&lt;/strong&gt;</td><td>&lt;strong&gt;Comments&lt;/strong&gt;</td></tr><tr><td>&lt;strong&gt;Beam-Balance&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Beam</td><td>home built</td><td></td><td>wood, 25&quot; l x 1&quot; h x 3/4&quot; w sealed with polyurethane varnish</td></tr><tr><td>C-clamp</td><td>Home Depot</td><td>1422-C</td><td>2 1/2&quot;</td></tr><tr><td>barrier</td><td>Home Depot</td><td></td><td>styrofoam, 18&quot; x 17 1/2&quot;</td></tr><tr><td>table (for both BB &amp;amp; BW)</td><td>generic office supply</td><td></td><td>37&quot; h x 30&quot; w x 60&quot; l</td></tr><tr><td>&lt;strong&gt;Name&lt;/strong&gt;</td><td>&lt;strong&gt;Company&lt;/strong&gt;</td><td>&lt;strong&gt;Catalog Number&lt;/strong&gt;</td><td>&lt;strong&gt;Comments&lt;/strong&gt;</td></tr><tr><td>&lt;strong&gt;Beam-Walk&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Beam</td><td>home built</td><td></td><td>wood 38-1/2&quot; l x 1-3/4&quot; h x 1&quot; w sealed with polyurethane varnish (~ 37&quot; off floor)</td></tr><tr><td>escape box</td><td>home built</td><td></td><td>woodpainted black 12 1/2 &quot; l x 9&quot; h x 7-1/4&quot; w</td></tr><tr><td>nails (pegs)</td><td></td><td></td><td>2&quot;</td></tr><tr><td>hinges</td><td></td><td></td><td></td></tr><tr><td>clamps</td><td></td><td></td><td></td></tr><tr><td>white noise machine</td><td>San Diego Instruments&lt;br/&gt; 9155 Brown Deer Rd, Suite 8 San Diego, CA 92121&lt;br/&gt; Phone: (858)530-2600</td><td></td><td>http://www.sandiegoinstruments.com/libraries/misc/datasheets/whitenoise.pdf</td></tr><tr><td>light</td><td>Home Depot</td><td></td><td></td></tr><tr><td>&lt;strong&gt;Name&lt;/strong&gt;</td><td>&lt;strong&gt;Company&lt;/strong&gt;</td><td>&lt;strong&gt;Catalog Number&lt;/strong&gt;</td><td>&lt;strong&gt;Comments&lt;/strong&gt;</td></tr><tr><td>&lt;strong&gt;Morris Water Maze&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>fiberglass pool</td><td>manufacturer unknown</td><td></td><td></td></tr><tr><td>(similar to one made by SDI)</td><td>San Diego Instruments</td><td>7000-0723</td><td>72&quot; diameter x 30&quot; deep (~ 500 gal)</td></tr><tr><td>plexiglass platform</td><td>hand-made by Maggie Parsley</td><td></td><td>10 cm diameter, 26&quot; tall with silicone applied to the surface of the platform to provide a gripping surface</td></tr><tr><td>(similar to one made by SDI)</td><td>SDI</td><td>7500-0272</td><td></td></tr><tr><td>plexiglass animal boxes w/ lids</td><td>UTMB Machine Shop</td><td></td><td>2 boxes, 10&quot; w x 16&quot; L x 9&quot; h</td></tr><tr><td>spot lights/ heat lamps</td><td>Home Depot</td><td></td><td>3 around pool, 2 over boxes to dry animals</td></tr><tr><td>AnyMaze</td><td>San Diego Instruments&lt;br/&gt; 9155 Brown Deer Rd, Suite 8 San Diego, CA 92121&lt;br/&gt; Phone: (858)530-2600</td><td>/9001</td><td>http://www.sandiegoinstruments.com/any-maze-video-tracking/</td></tr></tbody></table>

detecting behavioral deficits in rats after traumatic brain injury

外傷性脳損傷 (TBI) 両方の民間および軍事集団での増加率、TBI 今慢性的な疾病を考慮します。ただし、ほとんどの研究は、TBI の齧歯動物モデルにおける損傷の長期効果に します。ここでは、2 ヶ月までの 2 週間のような損傷後早期回 TBI の研究で確立された行動措置。これらのメソッドのいくつか以前で使用されている怪我後の後の時代まで非常に少数の研究所が 1 年間。ここでは、反射神経をテストするための短い神経学的評価、バランス、バランスとモーターの調整と赤字に敏感になることができますモリス水迷路のワーキング メモリーのバージョンをテストするビーム散歩をテストするビーム バランス メソッドを実証メモリを参照します。雄ラット処理され、バランス、神経学的に事前訓練を受けて、傍矢状洞流動打楽器の傷害 (FPI) または偽の傷害を受け取る前にモーターの調整をテストします。ラットは短い神経学的評価 (neuroscore)、ビーム バランスをテストすることができ・ ビーム歩行複数回水迷路のテスト中のみ一度。この違いは、ラットは、タスク、同じ動物でテストが試行を繰り返した場合、こうして結果を交絡を覚えることができるためです。1 受傷後 3 日からテスト、3 つの非認知タスクで有意差が検出された場合します。ただし、ビーム徒歩タスクの違い検出されなかった後時点で (後で 3 か月)。ビーム バランスで 3ヶ月と、neuroscore で 6 ヶ月で赤字が検出されました。傷害後、12 ヶ月ワーキング メモリの赤字を検出し、12 ヶ月でリファレンス ・ メモリに赤字が初めて登場しました。したがって、標準的な行動テストは FPI 後永続的な行動の赤字の有用な施策をすることができます。

Watch this Scientific Journal Video about Detecting Behavioral Deficits in Rats After Traumatic Brain Injury at JoVE.com

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

ここに示す行動テストの目的は、外傷性脳損傷後ラットにおける機能的障害を検出するためです。4 つの特定のテストは傷害の後の 1 年間に拡張する時特定の脳の領域への損傷を反映するように行動の赤字を検出するを掲載されています。

外傷性脳損傷後のラットの行動の赤字を検出

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, ...

detecting-behavioral-deficits-in-rats-after-traumatic-brain-injury

Universidad San Sebastian

Research

JoVE Journal

Behavior

17.8K ビュー.  University of Texas Medical Branch. ここに示す行動テストの目的は、外傷性脳損傷後ラットにおける機能的障害を検出するためです。4 つの特定のテストは傷害の後の 1 年間に拡張する時特定の脳の領域への損傷を反映するように行動の赤字を検出するを掲載されています。

ビデオ: Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury

Traumatic Brain Injury (TBI) afflicts more than 1.7 million people in the United States each year and even mild TBI can lead to persistent neurological impairments 1. Two pervasive and disabling symptoms experienced by TBI survivors, memory deficits and a reduction in seizure threshold, are thought to be mediated by TBI-induced hippocampal dysfunction 2,3. In order to demonstrate how altered hippocampal circuit function adversely affects behavior after TBI in mice, we employ lateral fluid percussion injury, a commonly used animal model of TBI that recreates many features of human TBI including neuronal cell loss, gliosis, and ionic perturbation 4-6.
	Here we demonstrate a combinatorial method for investigating TBI-induced hippocampal dysfunction. Our approach incorporates multiple ex vivo physiological techniques together with animal behavior and biochemical analysis, in order to analyze post-TBI changes in the hippocampus. We begin with the experimental injury paradigm along with behavioral analysis to assess cognitive disability following TBI. Next, we feature three distinct ex vivo recording techniques: extracellular field potential recording, visualized whole-cell patch-clamping, and voltage sensitive dye recording. Finally, we demonstrate a method for regionally dissecting subregions of the hippocampus that can be useful for detailed analysis of neurochemical and metabolic alterations post-TBI.
	These methods have been used to examine the alterations in hippocampal circuitry following TBI and to probe the opposing changes in network circuit function that occur in the dentate gyrus and CA1 subregions of the hippocampus (see Figure 1). The ability to analyze the post-TBI changes in each subregion is essential to understanding the underlying mechanisms contributing to TBI-induced behavioral and cognitive deficits. 
	The multi-faceted system outlined here allows investigators to push past characterization of phenomenology induced by a disease state (in this case TBI) and determine the mechanisms responsible for the observed pathology associated with TBI.

A multi-faceted approach to investigating functional changes to hippocampal circuitry is explained. Electrophysiological techniques are described along with the injury protocol, behavioral testing and regional dissection method. The combination of these techniques can be applied in similar fashion for other brain regions and scientific questions.

軽度の外傷性脳損傷後の海馬回路機能の改変に関する調査

Traumatic Brain Injury (TBI) afflicts more than 1.7 million people in the United States each year and even mild TBI can lead to persistent neurological ...

神経科学

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 ...

医学

Assessing Dominant-Submissive Behavior in Adult Rats Following Traumatic Brain Injury

Competition over resources such as food, territory, and mates significantly influences relationships within animal species and is mediated through social hierarchies that are often based on dominant-submissive relationships. The dominant-submissive relationship is a normal behavioral pattern among the individuals of a species. Traumatic brain injury is a frequent cause of social interaction impairment and the reorganization of dominant-submissive relationships in animal pairs. This protocol describes submissive behavior in adult male Sprague-Dawley rats after the induction of traumatic brain injury using a fluid-percussion model compared to naive rats through a series of dominant-submissive tests performed between 29 days and 33 days after induction. The dominant-submissive behavior test shows how brain injury can induce submissive behavior in animals competing for food. After traumatic brain injury, the rodents were more submissive, as indicated by them spending less time at the feeder and being less likely to arrive first at the trough compared to the control animals. According to this protocol, submissive behavior develops after traumatic brain injury in adult male rats.

The present protocol describes a rat model of fluid percussion-induced traumatic brain injury followed by a series of behavioral tests to understand the development of dominant and submissive behavior. Using this model of traumatic brain injury in conjunction with specific behavioral tests enables the study of social impairments following brain injury.

外傷性脳損傷後の成体ラットにおける優性服従行動の評価

Competition over resources such as food, territory, and mates significantly influences relationships within animal species and is mediated through social ...

行動学

Gathering Self-Initiated Rat Behavioral Data to Characterize Post-Stroke Deficits

Behavioral testing in rat models is frequently utilized for diverse purposes, including psychological, biomedical, and behavioral research. Many traditional approaches involve individual, one-on-one testing sessions between a single researcher and each animal in an experiment. This setup can be very time consuming for the researcher, and their presence may impact the behavioral data in unwanted ways. Additionally, traditional caging for rat research imposes a lack of enrichment, exercise, and socialization that would normally be typical for the species, and this context may also skew the results of behavioral data. Overcoming these limitations may be worthwhile for several research applications, including the study of acquired brain injury. Here, an example method is presented for automatically training and testing individual rat behavior in a colony cage without the presence of humans. Radio frequency identification can be utilized to tailor sessions to the individual rat. The validation of this system occurred in the example context of measuring skilled forelimb motor performance before and after stroke. Traditional characteristics of post-stroke behavioral impairments and novel measures enabled by the system are measured, including success rate, various aspects of pull force, bout analysis, initiation rate and patterns, session duration, and circadian patterns. These variables can be collected automatically with few limitations; though the apparatus removes experimental control of exposure, timing and practice, the validation produced reasonable consistency in these variables from animal to animal.

A system for acquiring data from self-initiated individual behavior sessions within a social colony cage setting is presented. The efficacy of this system is demonstrated using an automated skilled reach assessment, enabling the characterization of post-stroke motor impairments, potential behavioral alterations related to motivation, circadian variations, and other innovative dependent variables.

脳卒中後の欠損を特徴付けるための自発的なラット行動データの収集

Behavioral testing in rat models is frequently utilized for diverse purposes, including psychological, biomedical, and behavioral research. Many ...

Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes demonstrate the ability to record action potentials from individual or small groups of neurons. Such recorded signals have successfully been used to allow patients to interface with or control&#160;computers, robotic limbs, and their own limbs. However, previous animal studies have shown that a microelectrode implantation in the brain not only damages the surrounding tissue but can also result in functional deficits. Here, we discuss a series of behavioral tests to quantify potential motor impairments following the implantation of intracortical microelectrodes into the motor cortex of a rat. The methods for open field grid, ladder crossing, and grip strength testing provide valuable information regarding the potential complications resulting from a microelectrode implantation. The results of the behavioral testing are correlated with endpoint histology, providing additional information on the pathological outcomes and impacts of this procedure on the adjacent tissue.

We have shown that a microelectrode implantation in the motor cortex of rats causes immediate and lasting motor deficits. The methods proposed herein outline a microelectrode implantation surgery and three rodent behavioral tasks to elucidate potential changes in the fine or gross motor function due to implantation-caused damage to the motor cortex.

ラット皮質運動野の微小電極注入による機能的障害を評価するためにテスト行動の齧歯動物

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes ...

生物工学

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 ...

A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats

The purpose of this study was to establish and validate an animal brain ischemia model in the recovery and sequela stages. A middle cerebral artery occlusion/reperfusion (MCAO/R) model in male Sprague-Dawley rats was chosen. By changing the rat&#39;s weight (260&#8722;330 g), the thread bolt type (2636/2838/3040/3043) and the brain infarct time (2-3 h), a higher Longa&#39;s score, a larger infarct volume and a greater model success ratio were screened using the Longa&#39;s score and TTC staining. The optimum model condition (300 g, 3040 thread bolt, 3 h brain infarct time) was acquired and used in a 1-90 day observation period after reperfusion via assessment of sensorimotor functions and infarct volume. At these conditions, the bilateral asymmetry test had a significant difference from 1 to 90 days, and the grid-walking test had a significant difference from 1 to 60 days; both differences could be a suitable sensorimotor functional test. Thus, the most appropriate condition of a novel rat model in the recovery and sequela stages of brain ischemia was found: 300 g rats that underwent MCAO with a 3040 thread bolt for a 3 h brain infarct and then reperfused. The appropriate sensorimotor functional tests were a bilateral asymmetry test and a grid-walking test.

The&#160;purpose of this study is to establish and validate an animal model for research in the recovery and sequela stages of brain ischemia by testing brain infarction and sensorimotor function after middle cerebral artery occlusion/reperfusion (MCAO/R) after 1-90 days in rats.

ラットの急性脳卒中後の脳回復を評価する前臨床モデル

The purpose of this study was to establish and validate an animal brain ischemia model in the recovery and sequela stages. A middle cerebral artery ...

A Metric Test for Assessing Spatial Working Memory in Adult Rats Following Traumatic Brain Injury

Impairments to sensory, short-term, and long-term memory are common side effects after traumatic brain injury (TBI). Due to the ethical limitations of human studies, animal models provide suitable alternatives to test treatment methods, and to study the mechanisms and related complications of the condition. Experimental rodent models have historically been the most widely used due to their accessibility, low cost, reproducibility, and validated approaches. A metric test, which tests the ability to recall the placement of two objects at various distances and angles from one another, is a technique to study impairment in spatial working memory (SWM) after TBI. The significant advantages of metric tasks include the possibility of dynamic observation, low cost, reproducibility, relative ease of implementation, and low stress environment. Here, we present a metric test protocol to measure impairment of SWM in adult rats after TBI. This test provides a feasible way to evaluate physiology and pathophysiology of brain function more effectively.

Traumatic brain injury (TBI) is commonly associated with memory impairment. Here, we present a protocol to assess spatial working memory after TBI via a metric task. A metric test is a useful tool to study spatial working memory impairment after TBI.

外傷性脳損傷後の成人ラットの空間ワーキングメモリ評価のための測定基準試験

Impairments to sensory, short-term, and long-term memory are common side effects after traumatic brain injury (TBI). Due to the ethical limitations of ...

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 ...

mTBIラットモデルにおける傷害反応と行動評価の検証

Rat Model of Closed-Head Mild Traumatic Injury and its Validation

Animal models are crucial for advancing our understanding of mild traumatic brain injury (mTBI) and guiding clinical research. To achieve meaningful insights, developing a stable and reproducible animal model is essential. In this study, we report a detailed description of a closed-head mTBI model and a representative validation method using Sprague-Dawley rats to verify the modeling effect. The model involves dropping a 550 g mass weight from a height of 100 cm directly onto the head of a rat on a destructible surface, followed by a 180-degree turn. To assess the injury, rats underwent a series of neurobehavioral assessments 10 min post-injury, including time of loss of consciousness, first seeking-behavior time, escape ability, and beam balance ability test. During the acute and subacute stages following the injury, behavioral tests were conducted to assess motor coordination ability (Beam task), anxiety (Open Field test), and learning and memory abilities (Morris Water Maze test). The closed-head mTBI model produced a consistent injury response with minimal mortality and replicated real-life situations. The validation method effectively verified the model development and ensured the stability and consistency of the model.

著者スポットライト:外傷性脳損傷研究の進歩 - 正確な複製と迅速な評価のためのクローズドヘッドモデル 

Here, we present a closed-head mild traumatic brain injury (mTBI) rat model and its validation exhibiting remarkable similarity to human mTBI concerning behavioral manifestations during the acute and subacute stages.

閉鎖性軽度外傷のラットモデルとその検証

Animal models are crucial for advancing our understanding of mild traumatic brain injury (mTBI) and guiding clinical research. To achieve meaningful ...