Name: a battery of motor tests in a neonatal mouse model of cerebral palsy
Uploaded: 2016-11-03T12:30:00.000+00:00
Duration: 10 min 2 s
Description: Watch this Scientific Journal Video about A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy at JoVE.com

We would like to thank everyone at Shriners Hospital Pediatric Research Center, in particular Dr. Mickey Seltzer, of whom without his support, this work would not have been funded. In addition, we would like to thank Isha Srivastava, who contributed to early data collection and Amy He, who helped with the figures. This study was funded by Shriners Hospitals for Children. No funding source played a role in experimental design or decision to submit the paper for publication.

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The authors declare that they have no competing financial interests.

人間とげっ歯類の間で行わ行動試験は、ヒトの症状に直接関連性を持っている細胞および分子応答の間に重複がある場合ヒトの疾患を研究するための動物モデルを使用するとのみ関連します。小児疾患の研究の主な問題の一つは、多くの研究者が疾患プロセスのために重要であり得る発達の違いを考慮することなく、モデル、ならびに成体げっ歯類の行動評価を作成するために、成体げっ歯類を使用することです。 、7（7日間の齧歯類- - 32週出生後2日目に相当し28で例えば、ヒトCNSの開発）、これらの問題のため、小児疾患の利用に関する研究だけではなく、適切な調整後の発達時点があることが重要ですだけでなく、適切な運動、感覚や反射的発達行動を検討する行動試験を。それぞれの新しい新生児疾患モデルが開発されるようにこのように、厳密に携帯することを保証するために試験されなければなりませんそして、行動反応は、齧歯類とヒトの間で最も適切な翻訳可能なデータを提供します。 脳性麻痺は、大人になって存続運動障害、です。現在入手可能な脳性麻痺モデルの多くの1つの問題は、小児患者に見られる障害と相関することができ、再現、標準化された運動テストの欠如です。新生児マウスにおいて低酸素症、虚血、および炎症を組み合わせたこの新たなモデルでは、モータの動作は、新生仔マウスに特異的な一連の試験を用いて評価しました。主観性を減少させ、定量的な報告を高めるために、いくつかの試験は非常に特異的ではなく、標準化することができる措置を評価しやすい含むように修飾されています。また、フロント及び後肢評価を別々に行うことができ、右/左の差を決定することができます。テストのこの電池は、年齢の2週間まで新生仔マウスに特異的です。 このCPモデルは示しています歩行困難（歩行、後肢蹄の角度）、ならびに四肢固有の弱点（4肢のサスペンション、後肢懸垂）、および発達反射の欠損（反射を把握）。この研究において唯一の時点を調べたが、これらの障害は、時間の経過とともに追跡することができます。 そのような試験のフォックスのバッテリーや発達のマイルストーン15のHeyserの評価として、新生児に使用することができるテストの他の電池は、あります。しかし、これらのテストは、その応答新生児がまだ開発されているので、同じではないかもしれない大人に新生児を比較します。フォックスのバッテリーとHeyserのAssementテストが観察主観的な二分法との情報（yesまたはno）の評価ではなく、客観的なデータ（角度、強度などに基づいて姿勢）に依存しています。そのため、これらの試験の主観性のため、多くの科学者は、このように他の人と限界への比類のない、その結果を作り、基準を、適応追加、または削除しました特定の疾患または障害のベースライン赤字を確立するという点で、データの有用性をる。定性的および特に新生児をテストするために設計されている標準化された運動テストの一組を確立することにより、個々の研究グループからの結果を正確かつ確実に報告し、比較することができます。

げっ歯類を用いた小児傷害または疾病の新モデルを開発することにより、急速に神経損傷から回復するラットとマウスの両方の驚くべき能力にしばしば困難です。したがって、任意の新たな小児疾患モデルを検証するために、徹底的に細胞および分子の変化を調べることは、行動転帰と手に手を行く必要があります。多くの点で、機能的な行動回復は、治療または翻訳関連性の面で根本的な細胞の変化よりも重要な場合があります。研究者は、成人と新生児における傷害についての詳細を学ぶように、彼らの応答が非常に異なっており、両者の間に外挿することはできないことは明らかです。例えば、新生仔マウスは、神経成長因子、脳由来神経栄養因子、ニューロトロフィン3及び脊髄損傷1,2次グリア細胞株由来神経栄養因子の異なるレベルを表示します。また、新生児は、脳卒中3、Dの後、有意な血液脳関門漏出を有します末梢神経損傷4の後emonstrate皮質ニューロンの再配置、および遅延または脊髄損傷および低酸素虚血5,6次アストログリオーシスを遅らせてきました。したがって、並進小児科の研究が発達同等のモデルを使用し、それらのモデルは、分子/細胞の変化と年齢に応じた行動試験の両方で評価されることことが重要です。 毎年1000年出生（NIH）：脳性麻痺（CP）が3に影響する運動障害です。 CP児は、疾患の重症度に応じて、症状や合併症の条件の範囲を示します。運動と協調の難しさは、モータの発達のマイルストーンに到達するの遅れに伴い、最も一般的な兆候です。他の徴候は、異常な筋緊張を（増加または減少のいずれか）が含まれ、細かい運動能力、歩行困難、過度のよだれや嚥下、音声遅延（NIH）を減少させました。 CPの根本的な原因はあると考えられています、または1年間の産後までの前または周産期中の酸素および/または脳への血流の欠如。さらに、炎症は、現在CPの開発における重要な要素であると考えられています。 CPの例大半は脳室周囲白質軟化症（PVL）として知られる心室、周りの白質損傷に関連しています。この神経学的特徴は、CPに至る初期の侮辱は、オリゴデンドロサイトが傷害に対して最も脆弱な脳の発達の期間中に発生したことを示唆しています。 32週の妊娠 - 人間の急速なオリゴデンドロサイトの成長の期間、オリゴデンドロサイトが傷害に最も影響を受けやすいもの期間は、24の間です。げっ歯類では、同等の期間は、出生後の日2 - 7 7、およびCPは、このモデルにおいて誘導されたときです。 ここで概説試験を実施するために使用されたCPの新生児マウスモデルは、INJを作成するために、炎症と低酸素症および虚血を兼ね備えより良い模倣人間CPで見られる神経変性ユリィ。このモデルは、人間のCP患者に似た個別の運動障害、ならびに個別の白質損傷を欠いているCPの他の動物モデルにおいて観察された主要な欠点のいくつかに対処しています。同じモデルを使用して、共同研究者による以前の研究では、このように優れたCP 8と子供に見られるPVLをエミュレートし、炎症の添加は白質の損傷を増強することを実証しました。以前のデータを踏まえ、本稿では、動物の年齢などの運動行動の変化を評価するために、新生児モータの総合テストバッテリーを提示します。

<table><tbody><tr><td></td><td></td><td></td><td></td></tr><tr><td>C57BL/6 mice</td><td>Charles River Laboratories</td><td>STRAIN CODE: 027&amp;nbsp;</td><td>C57BL/6NCrl is the exact strain we use</td></tr><tr><td>Anesthesia Dish, PYREX&amp;trade; Crystallizing Dish</td><td>Corning Life Sciences Glass&amp;nbsp;</td><td>3140125</td><td>Capacity: 25.03 oz. (740ml); Dia. x H: 4.92 x 2.55 in. (125 x 65mm). However, any small round glass container will work. A 2 cup capacity pyrex food storage bowl with flat bottom will also work and is much cheaper (Pyrex model number: 6017399).</td></tr><tr><td>Covered lead ring</td><td>Fisher Scientific</td><td>S90139C</td><td>Lead ring for stablizing flasks in a water bath. It is used inside the anesthesia dish.</td></tr><tr><td>Scalpel Blade #11</td><td>World Precision Instrucments, Inc.</td><td>500240</td><td></td></tr><tr><td>Small Vessel Cauterizer</td><td>Fine Science Tools</td><td>18000-00</td><td></td></tr><tr><td>Micro Hook</td><td>Fine Science Tools</td><td>10064-14</td><td></td></tr><tr><td>Vetbond Suture Glue</td><td>3M</td><td>1469SB</td><td>n-butyl cyanoacrylate adhesive</td></tr><tr><td>Lipopolysaccharide</td><td>Sigma Life Science</td><td>L4391</td><td>Lipopolysaccaride from E.coli 0111:B4, gamma irradiated</td></tr><tr><td>12 x 12 inch opaque box</td><td>Acrylic Display Manufacturing: A division of Piasa Plastics</td><td>C4022</td><td>Colored Acrylic 5-Sided Cube, 3/16&quot; Colored Acrylic, 12&quot;W x 12&quot;D x 12&quot;H;&amp;nbsp; http://www.acrylicdisplaymfg.com/html/cubes_19.html</td></tr><tr><td>Camera/camcorder</td><td>JVC</td><td>GC-PX100BUS</td><td>Any camcorder that works well in low light and can be imported and edited. We use the JVC GC-PX100 Full HD Everio Camcorder.</td></tr><tr><td>Covidien Tendersorb&amp;trade; Underpads</td><td>Kendall Healthcare Products Co</td><td>7174</td><td></td></tr><tr><td>WypAll L40</td><td>Kimberly-Clark Professional</td><td>5600</td><td>Any surface with moderate grip will do</td></tr><tr><td>Surface at 45 degree incline</td><td></td><td></td><td>We use a cardboard box.</td></tr><tr><td>Thin wire from a pipe cleaner</td><td>Creatology</td><td>M10314420</td><td>Any pipe cleaner from any craft store will work.</td></tr><tr><td>50mL conical tube</td><td>Falcon</td><td>352070</td><td></td></tr><tr><td>Fiberglass Screen Wire</td><td>New York Wire&amp;nbsp; www.lowes.com</td><td>14436</td><td>Any supplier can be used as long as their screen is 16 x 16 or 18 x 16</td></tr><tr><td>Razor blade</td><td>Fisherbrand</td><td>12-640</td><td>A wooden stick applicator or wooden part of a cotton-tipped swab will also work.</td></tr><tr><td>OPTIX 24-in x 4-ft x 0.22-in Clear Acrylic Sheet to make Clear Acrylic Walkway</td><td>PLASKOLITE INC</td><td>1AG2196A</td><td>Clear acrylic (1/8&quot; thick) with sides and a top to limit exploration. We bought a sheet of acrylic from a local hardware store and had them cut it to size. (2) 2&quot; x 2&quot;; (3) 2&quot; x 18&quot;; (1) 2&quot; x 15.5&quot;; (1) 2&quot; x 3&quot;. Using clear tape, tape all sides together, with the 15.5&quot; piece on top. Tape the 3&quot; piece to the end of the 15.5&quot; piece to create a flap/entryway for the mice. Alternatively, part or all of the walkway can be glued together, and only taping on the top pieces. This design will allow for the walkway to be opened for easy cleaning.</td></tr><tr><td>Protractor</td><td>Westscott</td><td>ACM14371</td><td></td></tr></tbody></table>

a battery of motor tests in a neonatal mouse model of cerebral palsy

As the sheer number of transgenic mice strains grow and rodent models of pediatric disease increase, there is an expanding need for a comprehensive, standardized battery of neonatal mouse motor tests. These tests can validate injury or disease models, determine treatment efficacy and/or assess motor behaviors in new transgenic strains. This paper presents a series of neonatal motor tests to evaluate general motor function, including ambulation, hindlimb foot angle, surface righting, negative geotaxis, front- and hindlimb suspension, grasping reflex, four limb grip strength and cliff aversion. Mice between the ages of post-natal day 2 to 14 can be used. In addition, these tests can be used for a wide range of neurological and neuromuscular pathologies, including cerebral palsy, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, neurodegenerative diseases, and neuromuscular disorders. These tests can also be used to determine the effects of pharmacological agents, as well as other types of therapeutic interventions. In this paper, motor deficits were evaluated in a novel neonatal mouse model of cerebral palsy that combines hypoxia, ischemia and inflammation. Forty-eight hours after injury, five tests out of the nine showed significant motor deficits: ambulation, hindlimb angle, hindlimb suspension, four limb grip strength, and grasping reflex. These tests revealed weakness in the hindlimbs, as well as fine motor skills such as grasping, which are similar to the motor deficits seen in human cerebral palsy patients.

マウスは、試験のパラダイムを学ぶことは交絡変数ではなかったように、各時点に別のマウスを用いて、P13（1週間以下の手術）にP7（手術後24時間）から試験しました。マウスは、この時点で最大の赤字を示したようP8は、代表的な結果として選択しました。 クロールからウォーキングへの移行は、CP新生児マウスにおける遅延され 人間のCP患者はつま先歩きからシザリング歩行に至るまで、歩行異常を持っています。このCPモデルディスプレイは人間に似赤字を歩行したように、歩行を評価しました。マウスはまっすぐ歩行中の歩行対称性と肢足の動きに採点しました。 CP 1.083±：手術後48時間（PND 8）では、CPのマウスは、それらの偽の対応（平均歩行スコアと比較して少ない対称性四肢運動と「クロール」歩行を持っていました偽1.639±0.4859対0.6337、N = 12、N = 9; P &lt;0.05、 図10）。一週間では、CPおよび偽マウスの両方が（データは示していない）歩行に移行しました。 <img alt="図10" src="/files/ftp_upload/53569/53569fig10.jpg" /> 図10. CPマウス子犬は歩行しないだけでなく、シャムス。シャムマウス（黒棒）は1.639±0.4859の平均スコアを持っていた（n = 9）、彼らの歩行発達を意味する非対称性四肢運動と遅いクロールの間に入ります。 CPマウス（灰色のバー）1.083±0.6337（N = 12）の平均スコアを受け、彼らの歩行は発展途上であり、非対称の四肢の動きを持っている傾向があるという意味。データは、平均±SEMとして表されます。 *はp &lt;0.05である。 <a href="https://www.jove.com/files/ftp_upload/53569/53569fig10large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a> ホアヒンフット角度はCPで増加するdlimb 歩行に加えて、後肢足角を評価しました。八日齢の偽の仔マウスは、直線（ 図2の中を歩いたときに後足をスプレイしているHILマウスに比べ、前方を向いた彼らの後足で歩く;平均角度：CP 77.48±9.848、N = 9、対54.54±シャム8.043、N = 11; P &lt;0.0001、 図11）。子犬が彼らの歩行を安定化し、バランスと協調を支援するために、その後部足の角度を大きくする必要があるという点で、この増加した角度は、歩行不安定性と相関します。 <img alt="図11" src="/files/ftp_upload/53569/53569fig11.jpg" /> 図11. CPマウス子犬スプレイは、彼らの後足ウォーキング。CPマウス（黒棒）77.48±8.043（N = 11）の彼らの後肢間の平均角度を持って、偽マウス（グレーBしばらく<html> ARS）は54.54±9.848（平均角度を持っているのn = 9）。データは、平均±SEMとして表されます。 ****はp &lt;0.0001である。 <a href="https://www.jove.com/files/ftp_upload/53569/53569fig11large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a> CPのマウスは、赤字を表示しないときに表面復原 いくつかのCP患者は、トランク制御（Heyrman ら。、2013）が損なわれているように、テストを正す面が含まれていました。また、前庭系は、立ち直りの必要性を検出する必要がある、いくつかのCP患者23内の前庭障害があります。シャム対照と比較して、立ち直り時CPマウスは有意な障害を示していない（データは示さず）。 CPのマウスは、負の走地性テストにシャムと同じを実行します 。。 &quot;FO：キープtogether.within-ページは=&quot;トン配向上り坂に1 &quot;&gt;負の走地性は若い子犬に運動協調をテストするために使用されたマウスは、傾斜面に下り坂面した場所であることによってチャレンジする遅延や障害が障害を示している可能性があります（データは示していない）偽のマウスと比較して、負の走地性でチャレンジした場合に協調、バランス、または前庭入力に。CPマウスは全く障害を示さない。さらに、CPマウスは再配向もうに対して一方側に回転する選好を示しませんでした。 フロントリム懸垂試験は、10日より前のマウスに適しています CP患者は、このような把握などの細かい運動能力、で筋肉の緊張と赤字が低下しています。このマウスモデルの弱点をテストするために、我々は、フロント肢懸垂試験を用います。さらに、このモデルは、一方的な虚血性傷害を使用して両面らしこの懸濁試験を用いて決定することができます。このテスト10日15歳以上のマウスのためのより良いです。 8日齢に、損傷後2日、CPおよび偽マウスの間に有意差はなかった（データは示さず）。 後肢強度は、CPマウスにおいて減少します 人間のCP患者はしばしば、モータ制御と強度不足にブレースや支援歩行デバイスが必要です。ヒトへのげっ歯類CPモデルを比較するために、後肢強度は後肢懸垂試験を用いて評価しました。 CP 3.468±0.5561、N = 13、対偽3.891±0.1329、N = 13; pは&lt;：コニカルチューブの側面から吊り下げたときのスコアをぶら下げの減少により示されるように、CPマウスは後肢吊りスコア（、後肢弱さを示しました0.05、 図 12）。差異は後肢懸垂時間で観察されなかった（データは示さず）。したがって、ヒトのCP患者と同様に、CPマウスはhindlを実証しますIMB（脚）脱力。 <img alt="図12" src="/files/ftp_upload/53569/53569fig12.jpg" /> 図12.シャムマウスは 、偽マウス（黒棒）より後肢分離し、したがって強い後肢の姿勢を示し3.891±0.1329の平均吊りスコアで。少しけど （N = 13）CPマウスよりも彼らの後肢で有意に強いです 3.468±0.5561（N = 13）の平均吊りスコアでCPマウス（灰色のバー）よりもチューブの端にぶら下がったとき。データは、平均±SEMとして表されます。 *はp &lt;0.05である。 <a href="https://www.jove.com/files/ftp_upload/53569/53569fig12large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a> 握力は、次のCP傷害低減されます すべての4つの足で把握することで、げっ歯類のために重要です登山や凹凸面全体に実行されているという点。グリップは、主桁で、重要な持続的な強さではなく、器用さや直線力を必要とし、24を PAWS。マウスを反転ワイヤメッシュスクリーン上に彼らの体重を保持するために必要でした。 CPマウスは彼らのグリップを維持することができませんでしたし、これらのマウスは、有意に低い角度で落ちた（四肢平均角度：CP 75.627±24.48、N = 11、対偽96.57±10.836、N = 9; P &lt;0.05、 図13）。このデータは、CPマウスにおける握力の有意な欠陥があることを示します。 <img alt="図13" src="/files/ftp_upload/53569/53569fig13.jpg" /> 13. CPマウスがシャムス。シャムマウス（黒棒） よりも弱いグリップを持っている図は、96.57±10.836の平均反転角度に把握（N = 9）ことができます。 CPマウス（灰色のバー）が唯一の75.627±24.48（N = 11）の反転角度に到達することができます。データは、平均±SEMとして表されます。 * pは0; 0.05。 <a href="https://www.jove.com/files/ftp_upload/53569/53569fig13large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a> 把握反射赤字はCPマウスにおいて明らかです 総運動障害に伴い、微細運動の動きはまた、CP患者25,26に損なわれています。ヒトでの把握反射が出生時に存在し、約5消える - 6ヶ月。しかし、このような誇張された速度や強度把握、把握するのに失敗、または把持反射の再来として把握反射の変化、年齢の6ヶ月後に、すべてのは、神経系への損傷を示しています。 CPモデルに把握比較するために、反射的把持赤字が決定しました。 損傷後48時間で、CPマウス（平均足把持反射を把握するの減少を実証します48時間で：CP 2.429±0.9376、N = 14、対3.214±0.8018偽、N = 14; P &lt;0.05、 図14A）。前肢の右肢の好みのわずかな、しかし有意ではない増加があった（データは示さず）。そこ後足の大幅な右足の好みだった（CP 75.0±42.74であり、n = 14、偽17.86±54.09対はn = 14; P &lt;0.005、 図14B）。 、特段の足の嗜好と;：一週間損傷後、CPマウス（P &lt;0.05、 図14C CP 2.75±1.035、N = 8を、対3.80±0.6325、N = 10を偽平均足は1週間で把握）の赤字を把握表示します。 <img alt="図14" src="/files/ftp_upload/53569/53569fig14.jpg" /> 図14. CPのマウスは、後足で、負傷脳領域に対側を把持赤字を持っています。 （A）48時間後の損傷（PND 8）、CPマウス（灰色のバー）、平均して、とスティックを把握、偽アニマよりも少ない足LS（黒いバー）。（B）CPマウス（灰色のバー）が、左後肢（損傷に同側）を使用してとは対照的に（損傷に対側）の右後足に把握するためのプリファレンスを表示します。シャムマウス（黒棒）は、この右足の好みは表示されません。右足の好みは次のように計算された（ - / [右足+左足+両足] * 100 [右足の足左]）を（C）一週間損傷後、CPマウス（灰色のバー）と比較して依然として赤字を把握示します。シャムス（黒いバー）。データは、平均±SEMとして表されます。 * P &lt;0.05、**は、p &lt;0.005である。 <a href="https://www.jove.com/files/ftp_upload/53569/53569fig14large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a> CPのマウスは、クリフ嫌悪中にエッジから離れ向けます 崖回避テストは、阿波を回すために、マウスの固有の恐怖に依存しています安全性に向かって急な崖と頭からyの。いくつかのCP患者は前庭困難だけでなく、障害者のモータ制御を持っていますが、CPのマウスは、このテスト上の任意の障害を示しませんでした。

Watch this Scientific Journal Video about A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy at JoVE.com

A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy

Presented is a concise battery of mouse neonatal motor tests. Using these tests, neonatal motor deficits can be demonstrated in a variety of neonatal motor disorders. By having a standardized set of tests, results from different studies can be compared, allowing for better and accurate reporting between groups.

脳性麻痺の新生児マウスモデルにおける運動テストのバッテリー

As the sheer number of transgenic mice strains grow and rodent models of pediatric disease increase, there is an expanding need for a comprehensive, ...

a-battery-of-motor-tests-in-a-neonatal-mouse-model-of-cerebral-palsy

Research

JoVE Journal

Medicine

24.0K ビュー.  Lewiz Katz School of Medicine at Temple University. Presented is a concise battery of mouse neonatal motor tests. Using these tests, neonatal motor deficits can be demonstrated in a variety of neonatal motor disorders. By having a standardized set of tests, results from different studies can be compared, allowing for better and accurate reporting between groups.

ビデオ: A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy

Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease

Sensitive and reliable behavioral outcome measures are essential to the evaluation of potential therapeutic treatments in preclinical trials for many neurodegenerative diseases. In Parkinson's disease, sensorimotor tests sensitive to varying degrees of nigrostriatal dysfunction are fundamental for testing the efficacy of potential therapeutics. Reliable and quite elegant sensorimotor measures exist for rats, however many of these tests measure sensorimotor asymmetry within the rat and are not entirely suitable for the newer genetic mouse models of PD. We have put together a battery of sensorimotor tests inspired by the sensitive tests in rats and adapted for mice. The test battery highlighted in this study is chosen for a) its sensitivity in a wide variety of mouse models of PD, b) its ease in implementing into a study, and c) its low expense. These tests have proven useful in characterizing novel genetic mouse models of PD as well as in testing potential disease-modifying therapies.

In Parkinson's disease and movement disorders in general, sensitive and reliable behavioral assays are essential for testing novel potential therapeutics. Here, we describe a manageable battery of sensorimotor tests for mice that are sensitive to varying degrees of injury to the nigrostriatal system and useful for preclinical studies.

パーキンソン病のマウスモデルにおける感覚運動機能の評価

Sensitive and  reliable behavioral outcome measures are essential to the evaluation of  potential therapeutic treatments in preclinical trials for many  ...

行動学

Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore by rearing and touching the walls of the cylinder with their forelimb paws for postural support. Following ischemic injury to the forelimb sensorimotor cortex, rats rely more heavily on their unaffected forelimb paw for postural support resulting in fewer touches with their affected paw which is termed forelimb asymmetry. In contrast, focal ischemic damage in the mouse brain fails to result in comparable consistent deficits in forelimb asymmetry. While forelimb asymmetry deficits are infrequently observed, mice do demonstrate a novel behaviour post stroke termed &#8220;paw-dragging&#8221;. Paw-dragging is the tendency for a mouse to drag its affected paw along the cylinder wall rather than directly push off from the wall when dismounting from a rear to a four-legged stance. We have previously demonstrated that paw-dragging behaviour is highly sensitive to small cortical ischemic injuries to the forelimb motor cortex. Here we provide a detailed protocol for paw-dragging analysis. We define what a paw-drag is and demonstrate how to quantify paw-dragging behaviour. The cylinder test is a simple and inexpensive test to administer and does not require pre-training or food deprivation strategies. In using paw-dragging analysis with the cylinder test, it fills a niche for predicting cortical ischemic injuries such as photothrombosis and Endothelin-1 (ET-1)-induced ischemia &#8211; two models that are ever-increasing in popularity and produce smaller focal injuries than middle cerebral artery occlusion. Finally, measuring paw-dragging behaviour in the cylinder test will allow studies of functional recovery after cortical injury using a wide cohort of transgenic mouse strains where previous forelimb asymmetry analysis has failed to detect consistent deficits.

Classical forelimb asymmetry analysis of the cylinder test is routinely used to assess behavioural deficits in rats following brain injury or stroke; however, it fails to detect consistent deficits in mice. This study demonstrates that quantifying paw-dragging behaviour is a more sensitive analysis of brain injury in mice.

ポウ·ドラッグ：小説、マウスシリンダー試験の感度分析

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore ...

Measuring Motor Coordination in Mice

Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such as emotionality or cognition can be assessed, however, it is vital to determine whether the motor capabilities of e.g. a mutant or lesioned mouse allow such an assessment. Performance on a maze task requiring strength and coordination, such as the Morris water maze, might well be impaired in a mouse by motor, rather than cognitive, impairments, so it is essential to selectively dissect the latter from the former. For example, sensorimotor impairments caused by NMDA antagonists have been shown to impair water maze performance2. 
Motor coordination has traditionally been assessed in mice and rats by the rotarod test, in which the animal is placed on a horizontal rod that rotates about its long axis; the animal must walk forwards to remain upright and not fall off. Both set speed and accelerating versions of the rotarod are available.
The other three tests described in this article (horizontal bar, static rods and parallel bars) all measure coordination on static apparatus. The horizontal bar also requires strength for adequate performance, particularly of the forelimbs as the mouse initially grips the bar just with the front paws. 
Adult rats do not perform well on tests such as the static rods and parallel bars (personal observations); they appear less well coordinated than mice. I have only tested male rats, however, and male mice seem generally less well coordinated than females. Mice appear to have a higher strength:weight ratio than rats; the Latin name, Mus musculus, seems entirely appropriate. The rotarod, the variations of the foot fault test12 or the Catwalk (Noldus)15 apparatus are generally used to assess motor coordination in rats.

Protocols are presented for two established motor coordination tasks, the accelerating rotarod and horizontal bar, also two tests developed in Oxford recently, the static rods and parallel bars. These tests can detect motor impairments potentially of interest in their own right, as well as being possible variables in tests of other areas of behavior.

マウスにおける運動協調性の測定

Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such ...

神経科学

Neurodevelopmental Reflex Testing in Neonatal Rat Pups

Neurodevelopmental reflex testing is commonly used in clinical practice to assess the maturation of the nervous system. Neurodevelopmental reflexes are also referred to as primitive reflexes. They are sensitive and consistent with later outcomes. Abnormal reflexes are described as an absence, persistence, reappearance, or latency of reflexes, which are predictive indices of infants that are at high risk for neurodevelopmental disorders. Animal models of neurodevelopmental disabilities, such as cerebral palsy, often display aberrant developmental reflexes, as would be observed in human infants. The techniques described assess a variety of neurodevelopmental reflexes in neonatal rats. Neurodevelopmental reflex testing offers the investigator a testing method that is not otherwise available in such young animals. The methodology presented here aims to assist investigators in examining developmental milestones in neonatal rats as a method of detecting early-onset brain injury and/or determining the effectiveness of therapeutic interventions. The methodology presented here aims to provide a general guideline for investigators.

Behavioral testing is the gold standard for determining outcomes following brain injury, and can identify the presence of developmental disabilities in infants and children. Neurodevelopmental reflexes are an early indicator of these abnormalities. A host of easily accomplished developmental reflex tests in the neonatal rodent were developed and described here.

新生ラット仔における神経発達レフレックステスト

Neurodevelopmental reflex testing is commonly used in clinical practice to assess the maturation of the nervous system. Neurodevelopmental reflexes are ...

Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the animal&#39;s wellbeing and health. There are numerous behavioral tests that may be applied. We selected a test for general locomotion, the open field test (OFT); a test for muscular strength, the mesh test (MT); and a test for coordination, the rotarod test (RR). Testing can be accomplished on a weekly or monthly basis. As a test for general locomotion, the OFT works by objectively monitoring movement parameters while the mouse is in an open field apparatus. The field is generally a 2&#39; x 2&#39; box, and the movements are recorded through laser sensing or through video capture. The mouse is placed in the center of the open field and allowed to move freely for the test. The MT uses the latency for a mouse to fall off an inverted screen as a measure of muscular strength. A mouse is placed on a screen, which is inverted over a clear box, and is timed for their latency to fall. Three trials are performed, with the best of the three trials scored for that day. A score of 60 s is the maximum time a mouse is left inverted. Mice are given a 5-min rest period between mesh test trials. Lastly, an accelerated protocol on the RR assesses motor coordination and endurance. During a trial, a mouse walks on a rotating rod as it increases in speed from 4 rpm to 40 rpm over 5 min. The trial ends when the mouse touches the magnetized pressure sensor upon falling. Each mouse undergoes three trials, and the best trial is scored for that day. This combined behavioral data allows for the global assessment of mobility, coordination, strength, and movement of the test animals. At least two out of the three behavioral testing measures must show improvement for an animal to qualify as having overall improved motor function.

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects of a disease or treatment on an animal's wellbeing. In order to globally assess motor functioning, we selected tests for general locomotion, muscular strength, and coordination: the open field test, the mesh test, and the rotarod test, respectively.

行動のバッテリー テスト評価の一般的な運動、筋肉の強さと連携マウス

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the ...

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 ...

医学

Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury

We performed unilateral carotid artery occlusion on CD-1 mice to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of neonatal HI brain injury by studying neurobehavioral functions in these mice compared to non-operated (i.e., normal) mice. During the study, Rice-Vannucci&#39;s method was used to induce neonatal HI brain damage in postnatal day 7-10 (P7-10) mice. The HI operation was performed on the pups by unilateral carotid artery ligation and exposure to hypoxia (8% O2 and 92% N2 for 90 min). One week after the operation, the damaged brains were evaluated with the naked eye through the semi-transparent skull and were categorized into subgroups based on the absence (&#34;no cortical injury&#34; group) or presence (&#34;cortical injury&#34; group) of cortical injury, such as a lesion in the right hemisphere. On week 6, the following neurobehavioral tests were performed to evaluate the cognitive and motor functions: passive avoidance task (PAT), ladder walking test, and grip strength test. These behavioral tests are helpful in determining the effects of neonatal HI brain injury and are used in other mouse models of neurodegenerative diseases. In this study, neonatal HI brain injury mice showed motor deficits that corresponded to right hemisphere damage. The behavioral test results are relevant to the deficits observed in human neonatal HI patients, such as cerebral palsy or neonatal stroke patients. In this study, a mouse model of neonatal HI brain injury was established and showed different degrees of motor deficits and cognitive impairment compared to non-operated mice. This work provides basic information on the HI mouse model. MRI images demonstrate the different phenotypes, separated according to the severity of brain damage by motor and cognitive tests.

We performed unilateral carotid artery occlusion on postnatal day 7-10 CD-1 mouse pups to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of HI brain injury. We studied neurobehavioral functions in these mice compared to non-operated normal mice.

新生児低酸素性虚血性脳損傷のマウス モデルにおける神経行動学的評価

We performed unilateral carotid artery occlusion on CD-1 mice to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of neonatal HI ...

A Controlled Mouse Model for Neonatal Polymicrobial Sepsis

Neonatal sepsis remains a global burden. A preclinical model to screen effective prophylactic or therapeutic interventions is needed. Neonatal mouse polymicrobial sepsis can be induced by injecting cecal slurry intraperitoneally into day of life 7 mice and monitoring them for the following week. Presented here are the detailed steps necessary for the implementation of this neonatal sepsis model. This includes making a homogeneous cecal slurry stock, diluting it to a weight- and litter-adjusted dose, an outline of the monitoring schedule, and a definition of observed health categories used to define humane endpoints. The generation of a homogeneous cecal slurry stock from pooled donors allows for the administration into many litters over time, reducing the variation between donors, and preventing the use of potentially toxic glycerol. The monitoring strategy used allows for the anticipation of survival outcome and the identification of mice that would later progress to death, allowing for an earlier identification of the humane endpoint. Two main behavioral features are used to define the health scores, namely, the ability of the neonatal mice to right themselves when placed on their back and their level of mobility. These criteria could potentially be applied to address humane endpoints in other studies of neonatal disease in mice, as long as a pilot study is performed to confirm accuracy. In conclusion, this approach provides a standardized method to model newborn sepsis in mice, while providing resources to assess animal welfare used to define early humane endpoints for challenged animals.

This protocol provides the necessary steps to establish and evaluate neonatal sepsis in 7-day-old mice.

新生児モデル敗血症マウスの制御モデル

Neonatal sepsis remains a global burden. A preclinical model to screen effective prophylactic or therapeutic interventions is needed. Neonatal mouse ...

免疫・感染学

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 ...

MouseWalkerを用いた脊髄損傷マウスの自発運動機能障害の定量化

Using the MouseWalker to Quantify Locomotor Dysfunction in a Mouse Model of Spinal Cord Injury

The execution of complex and highly coordinated motor programs, such as walking and running, is dependent on the rhythmic activation of spinal and supra-spinal circuits. After a thoracic spinal cord injury, communication with upstream circuits is impaired. This, in turn, leads to a loss of coordination, with limited recovery potential. Hence, to better evaluate the degree of recovery after the administration of drugs or therapies, there is a necessity for new, more detailed, and accurate tools to quantify gait, limb coordination, and other fine aspects of locomotor behavior in animal models of spinal cord injury. Several assays have been developed over the years to quantitatively assess free-walking behavior in rodents; however, they usually lack direct measurements related to stepping gait strategies, footprint patterns, and coordination. To address these shortcomings, an updated version of the MouseWalker, which combines a frustrated total internal reflection (fTIR) walkway with tracking and quantification software, is provided. This open-source system has been adapted to extract several graphical outputs and kinematic parameters, and a set of post-quantification tools can be to analyze the output data provided. This manuscript also demonstrates how this method, allied with already established behavioral tests, quantitatively describes locomotor deficits following spinal cord injury.

著者スポットライト:MouseWalkerを使用して脊髄損傷のマウスモデルにおける自発運動機能障害の定量化  

An experimental pipeline to quantitatively describe the locomotor pattern of freely walking mice using the MouseWalker (MW) toolbox is provided, ranging from initial video recordings and tracking to post-quantification analysis. A spinal cord contusion injury model in mice is employed to demonstrate the usefulness of the MW system.

脳性麻痺の新生児マウスモデルにおける運動テストのバッテリー

要約

さらに動画を探す

この動画の章

パーキンソン病のマウスモデルにおける感覚運動機能の評価

ポウ·ドラッグ：小説、マウスシリンダー試験の感度分析

マウスにおける運動協調性の測定

新生ラット仔における神経発達レフレックステスト

行動のバッテリーテスト評価の一般的な運動、筋肉の強さと連携マウス

新生児マウス脊髄圧縮損傷モデル

新生児低酸素性虚血性脳損傷のマウスモデルにおける神経行動学的評価

新生児モデル敗血症マウスの制御モデル

片性および反復性軽度外傷性脳損傷のマウスモデル

MouseWalkerを用いた脊髄損傷マウスモデルにおける自発運動機能障害の定量化

脳性麻痺の新生児マウスモデルにおける運動テストのバッテリー

要約

さらに動画を探す

この動画の章

パーキンソン病のマウスモデルにおける感覚運動機能の評価

ポウ·ドラッグ：小説、マウスシリンダー試験の感度分析

マウスにおける運動協調性の測定

新生ラット仔における神経発達レフレックステスト

行動のバッテリー テスト評価の一般的な運動、筋肉の強さと連携マウス

新生児マウス脊髄圧縮損傷モデル

新生児低酸素性虚血性脳損傷のマウス モデルにおける神経行動学的評価

新生児モデル敗血症マウスの制御モデル

片性および反復性軽度外傷性脳損傷のマウスモデル

MouseWalkerを用いた脊髄損傷マウスモデルにおける自発運動機能障害の定量化

行動のバッテリーテスト評価の一般的な運動、筋肉の強さと連携マウス

新生児低酸素性虚血性脳損傷のマウスモデルにおける神経行動学的評価