The authors would like to thank Irene Ma, Rose Tobais, and Jong Rho for their technical assistance. Funding was provided to MJE by the Department of Pediatrics at the University of Calgary, the Alberta Children&#8217;s Hospital Foundation (ACHF) and the Alberta Children&#8217;s Hospital Research Institute (ACHRI). The Postdoctoral fellowship for RM was provided by ACHF.

NOT: Tüm deneyler Hayvan Bakımı Kanada Konseyi çerçevesinde yürütülmüştür ve Calgary Üniversitesi, Hayvan Bakım Etik Komitesi tarafından kabul edildi. 1. Yetiştirme ve Hayvan Hazırlık <ol><li> Standart üreme protokollerine göre içi standart laboratuar hayvan tedarikçileri veya ırk yavrular hamile fareler Sipariş. </li><li> Karanlık döngüsü: Oda ısısı kontrol edilen bir sıçan muhafaza odası (21 ° C) &#39;de yiyecek ve su ad libitum girişleri, tüm hayvanlar, bir 12:12 saat ışık tutulur. </li><li> Yavrular doğum sonrası gün 21 (P21) ulaştığınızda, 3 ya da 4 eşcinsel gruplar annelerinden ve evinden yavrular vazgeçirmek. </li></ol> Hafif Travmatik Beyin Hasarı (HTBH) Aparatı 2. Set-up <ol><li> Işlemin başlamasından önce, arzu edilen kütleye değirmen ağırlıkları (örneğin, 150 g) eklenmiştir. Güvenli olta fi olmasını sağlayan ağırlık üst ucuna bir metal kordonuağırlığa duran. </li><li> Keskin bir jilet ile kalay folyo Puan. Attı kalay folyo sıçan vücut ağırlığını destekleyen ama ağırlığı ile baş etkisi aşağıdaki sıçan ivme engel olmaz emin olun. </li><li> O gergin böylece, bir koleksiyon sünger (38 x 25 x 15 cm 3) (Şekil 1) içeren Teyp şeffaf plastik (38 x 27 x 27 cm 3) yapılan U-şekilli aşamaya attı kalay folyo. </li><li> Şeffaf bir plastikten imal kılavuz tüpü altında doğru konumda U-şekilli plastik aşaması yerleştirin. </li><li> Bir kelepçe stand yerine plastik kılavuz tüp (2.2 cm çap x 1,5 m) tutun ve attı kalay folyo üzerinde 3,5 cm olacak şekilde kılavuz tüpü yerleştirin. </li><li> Ağırlık alt serbestçe 2,5 cm attı kalay folyo üstünde asılı sağlamak ağırlığı metal döngü içinde olta takın. </li><li> Güvenli kelepçe stand olta veriyoruz. NOT: kum midyesi ağırlık hayvan zinciriSıçan toplama sünger etkisi) düşen ise kalay folyo üzerinde 2.5 cm&#39;lik bir yüksekliğe p&#39;nin yeniden isabet engeller. </li><li> Olta ile plastik kılavuz tüp aracılığıyla kilo çekin ve 1.0 m altı köşeli anahtar iğne ile yerde tutun. </li></ol> HTBH 3. İndüksiyon <ol><li> Sıçanlar usul odasına P30 hareket kafesleri ulaştığınızda. </li><li> Izofluran odasında sıçan yerleştirin ve bir pençe veya kuyruk tutam olmayan duyarlı kadar hafifçe sıçan uyutmak. </li><li> Hızla düşen ağırlık yolu doğrudan kafa ile attı kalay folyo üzerindeki sıçan göğüs aşağı yerleştirin. Şekil 2 Bkz. Sıçan taşımak veya uyanma attı kalay folyo üzerine yerleştirilebilir önce, bir pençe veya kuyruk tutam olmayan duyarlı kadar izofluran odasına geri dönmek ve tekrar başlamak başlarsa. </li><li> Ağırlık plastik kılavuz tüp aracılığıyla dikey düşmek ve kafasına sıçan grev izin, Allen anahtar pimini çekin. The sıçan hızla sırtüstü pozisyonda bir 180 ° dönme ve arazi geçecek. </li><li> Hemen toplama sünger sıçan kaldırmak ve bir pamuk uçlu aplikatör ile sıçan başına topikal lidokain uygulamak. </li><li> Bir ticari olarak temin edilebilen ısıtma pedi üzerine ayarlayarak ısıtılır, temiz bir kafesi içinde sırt üstü pozisyonda sıçan yerleştirin. </li><li> Bir kronometre kullanarak veya dijital zamanlayıcı &quot;zaman sağa&quot; kazanır. Zaman sağa anestezi gelen uyanmak ve yüzüstü pozisyona sırtüstü pozisyondan çevirmek veya yürüyüş başlamak için sıçan tarafından alınan zamandır. </li><li> Normal davranış (vb keşfetmek, damat yürüme) kurtarıldı sonra ev kafesine sıçan dönün. </li><li> Tekrar bir HTBH gerektiren her ek sıçan 3,2-3,8 adımları. </li><li> Tekrarlayan HTBH deneyler için çoklu zaman noktalarında aynı sıçan prosedürü tekrarlayın. </li></ol> Sham Yaralanma 4. İndüksiyon <ol><li> Hafifçe AnestBir pençe veya kuyruk tutam olmayan duyarlı kadar izofluran ile sıçan hetize. </li><li> Hızla düşen ağırlık yolu doğrudan kafa ile attı kalay folyo üzerindeki sıçan göğüs aşağı yerleştirin. </li><li> Plastik kılavuz tüp allen anahtar pimini çekmeden kalay folyo sıçan çıkarın ve bir pamuk uçlu aplikatör ile sıçan başına topikal lidokain uygulamak. </li><li> Bir ticari olarak temin edilebilen ısıtma pedi üzerine ayarlayarak ısıtılır, temiz bir kafesi içinde sırt üstü pozisyonda sıçan yerleştirin. </li><li> &quot;Zaman-sağa&quot; elde etmek için bir kronometre veya dijital zamanlayıcı kullanın. </li><li> Normal davranış (vb keşfetmek, damat yürüme) kurtarıldı sonra ev kafesine sıçan dönün. </li></ol> Işın Yürüyüş Testi 8 ile HTBH 5. Doğrulama <ol><li> Usul odasına HTBH veya sahte yaralanma dönüş hayvanların indüksiyon sonrası 24 saat. </li><li> Temiz bir tutma kafesine sıçan aktarınve ev-kafesin açık uçlu kısmı kirişin dar ucunu karşıya şekilde ışın konik 165 cm dar sonunda sıçan ev kafes yerleştirin. NOT: konik ışın 165 cm uzunluğundadır. kirişin merkezi platform geniş ucunda 6 cm ve dar sonunda 1.75 cm bir genişliğe sahiptir. merkezi ışın zaman sıçan ayak makbuzları güvenliğini sağlayan çıkıntılar (2 cm genişliğinde ve merkez kiriş altında 2 cm) sahiptir. Test sırasında ışın düşebilir sıçanlara yaralanma riskini azaltmak için kiriş altına köpük dolgu yerleştirin. </li><li> Konik kiriş ve pozisyon geniş ucunda bir video kamera yerleştirin / video izlerken araştırmacı açıkça konik kirişin tüm uzunluğu boyunca sıçan hareketlerini görebilirsiniz sağlamak için video kamera yakınlaştırın. </li><li> Konik ışın geniş ucunda sıçan yerleştirin ve ev kafes kiriş üzerinde yürümek için teşvik ediyoruz. Sıçan konik ışın haçlar sonra, rei en az 60 saniye boyunca kendi ev-kafeste sıçan bırakınhedef konumu nForce. Bu Deneme # 1 ve analize dahil değildir. </li><li> Video kamerayı açın ve fare kiriş-yürüme görevi 4 ek kez (ev kafeste 60 sn takviye dönemleri muhafaza) tamamlamak için izin verir. Sıçan, tüm denemeler tamamlandıktan sonra, kendi ev-kafesine sıçan dönün. </li><li> Puan için, meydana ve zaman / süre her deneme için, ışın geçmeye arka bacak ayak-slip sayısını kaydedin. Her bir sıçan için ışın geçmeye arka bacak ayak-bordroları ve zaman ortalama sayısını hesaplamak için bu verileri kullanın. </li></ol>

<ol>
	<li>DeWitt, D., Perez-Polo, R., Hulsebosch, C., Dash, P., Robertson, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Challenges+in+the+development+of+rodent+models+of+mild+traumatic+brain+injury.">Challenges in the development of rodent models of mild traumatic brain injury.</a> Journal of Neurotrauma. 30, 688-701 (2013).</li><li>Xiong, Y., Mahmood, A., Chopp, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+traumatic+brain+injury.">Animal models of traumatic brain injury.</a> Nature Reviews Neuroscience. 14, 128-142 (2013).</li><li>Zhang, Z., Lerner, S., Kobiessy, F., Hayes, R., Wang, K., Yan, Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systems+biology+and+the+anostic+approach+to+drug+discovery+and+development+to+treat+traumatic+brain+injury.">Systems biology and the anostic approach to drug discovery and development to treat traumatic brain injury.</a> Systems Biology in Drug Discovery and Development: Methods and Protocols, Methods in Molecular Biology. , .</li><li>Viano, D., Casson, I., Pellmen, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Concussion+in+profession+football:+Biomechanics+of+the+struck+player+-+Part+14.">Concussion in profession football: Biomechanics of the struck player - Part 14.</a> Neurosurgery. 61, 313-327 (2007).</li><li>Marmarou, 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=A+new+model+of+diffuse+brain+injury+in+rats:+Part+1+-+Pathophysiology+and+biomechanics.">A new model of diffuse brain injury in rats: Part 1 - Pathophysiology and biomechanics.</a> Journal of Neurosurgery. 80, 291-300 (1994).</li><li>Mychasiuk, R., Farran, A., Esser, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+an+experimental+rodent+model+of+pediatric+mild+traumatic+brain+injury.">Assessment of an experimental rodent model of pediatric mild traumatic brain injury.</a> Journal of Neurotrauma. 31 (8), (2014).</li><li>Kane, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+mouse+model+of+human+repetitive+mild+traumatic+brain+injury.">A mouse model of human repetitive mild traumatic brain injury.</a> Journal of Neuroscience Methods. 203, 41-49 (2012).</li><li>Schallert, T., Woodlee, M., Fleming, S., Krieglstein, J., Klumpp, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Disentangling+multiple+types+of+recovery+from+brain+injury.">Disentangling multiple types of recovery from brain injury.</a> Pharmacology of Cerebral Ischemia. , (2002).</li><li>Mychasiuk, R., Hehar, H., Farran, A., Esser, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mean+Girls:+Sex+differences+in+the+effects+of+mild+traumatic+brain+injury+on+the+social+dynamics+of+juvenile+rat+play+behaviour.">Mean Girls: Sex differences in the effects of mild traumatic brain injury on the social dynamics of juvenile rat play behaviour.</a> Behavioural Brain Research. 259, (2014).</li><li>Centers for Disease Control and Prevention. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Report to congress on mild traumatic brain injury in the United States: Steps to prevent a serious public health problem. , 1-47 (2003).</li></ol>

No competing financial interests exist.

Reliable modelling systems are needed to effectively cultivate basic science research that has significant translational validity. In response to rising occurrences and popular media, the investigation of mTBI and concussion has become a priority in many disciplines. However, despite increased research, there have been only incremental improvements in therapeutic strategies and treatment options 3. This lack of progress may be partially due to a discrepancy between the modeling systems employed and actual injury etiology. The majority of studies utilized rodent models that failed to reproduce the important biomechanical forces and appropriate post-injury symptomology. The current human definition of mTBI specifies that the injury results from acceleration and deceleration forces associated with a blunt trauma 10. The modified weight drop technique described here is therefore an ideal model for the study of mTBI and concussion because it uses a glancing impact to cause rapid rotational acceleration and deceleration to the head of an unrestrained animal, mimicking the biomechanical forces identified in sports-related injuries and automobile accidents. In addition, this model is easily adapted to examine repetitive mTBI, a phenomena that is emerging as a serious medical and socioeconomic issue. Studies indicate that rodents may be exposed to a series of 10 distinct mTBIs with minimal mortality 7. Finally, the method is inexpensive and can be carried out rapidly, allowing for high-throughput examination of a many therapeutic compounds and treatment regiments. 
Just as with any procedural technique, certain aspects of the protocol are particularly important to the generation of reliable results. First, the tin foil needs to be scored effectively. If the tin foil is not properly scored, the force imparted by the weight during the glancing impact will not be enough to propel the juvenile rat through the tin foil onto the collection sponge. In these situations, the rat will remain in the starting position (chest down on the tin foil) and the mTBI will result from the blunt trauma from the weight impacting the stationary head, not the rotational acceleration and deceleration desired. Second, during the induction of the mTBI and the sham injury, the level of anesthetic applied to each rat should be consistent. Owing to the fact that time-to-right is used as marker of mTBI, the researcher should try to ensure that animals receiving a mTBI and animals receiving a sham injury are exposed to similar levels of anesthetic. A major advantage to this technique over many other TBI procedures is the low level and duration of anesthesiology. However, the juvenile rat needs to be non-responsive to a toe or tail pinch to ensure they do not wake-up on the stage before the injury is induced. Finally, in order to maintain a consistent injury etiology, the positioning of the rat&#8217;s head is particularly important. Ideally the weight should impact the center of the dorsal surface of the head. Caution should be taken to avoid positioning the path of the weight too near the caudal/posterior portion of the head, as impacting the brainstem and cerebellum is associated with increased mortality and seizure activity. 
Based upon the biomechanical pathophysiology of injury induction and the behavioural outcomes examined, the modified weight-drop technique appears to be a reliable model for the investigation of paediatric mTBI and concussion. Although preliminary studies of this novel model have assessed some basic molecular and structural changes 7 future studies will be needed to ascertain how the brain responds to a mTBI with this injury etiology. An in-depth analysis of the neuroanatomical and biological changes that occur at the cellular and epigenetic level would increase model validity and translational applicability. In addition to stimulating the generation of targeted pharmacological therapies, understanding the pathophysiological changes that occur in the brain in response to mTBI and concussion would also direct the research related to clinical biomarkers that have the ability to predict outcomes following injury.

Orta-şiddetli travmatik beyin hasarı (TBI), çok az teknikler hafif ikna etmek için geliştirilmiştir nesil için pek yaygın olarak kullanılan yöntemler olmasına rağmen, kemirgenlerde kafa yaralanmaları kapattı. Hafif travmatik beyin hasarı (HTBH) üç kat daha sık 1 kombine orta ve şiddetli beyin hasarı daha olması nedeniyle, HTBH güvenilir bir model araştırması ile ilgili patofizyolojisi, nörobiyolojik ve davranışsal sonuçları ve tedavi stratejileri kolaylaştırmak için gereklidir. Örneğin, 200&#39;ün üzerinde olmuştur son on yılda, mevcut hayvan modellerinde 2 sınırlamaları kısmen TBI 3 tedavisi için ilaç klinik araştırmaları başarısız oldu. Modelleme sistemleri öteleme araştırma çalışmaları için oluşturulan zaman, bulguların uygulanabilirliği uygulanan modelin geçerliliği bağlıdır. HTBH / sarsıntının çalışma için, güvenilir bir hayvan modeli sadece biyomekanik güçler yanıtlayanların taklit olmazyaralanma etiyolojisi için Sible, ama aynı zamanda klinik olarak ilgili nüfus tarafından bildirilen ile tutarlı belirtiler neden olur. Çocuk HTBH için yüksek risk altındadır için Ayrıca, en iyi model sistemleri, yetişkin eşdeğer yanı sıra genç ve çocuk kemirgenler için geçerli olacaktır. Sporcular mTBIs veya sarsıcı beyin yaralanınca hangi koşullar biyomekanik analizler yaralanma için en kritik belirleyici faktörlerin hızlı kafa hızlanma ve yüksek hız etkileri 4 olduğunu göstermektedir. Şu anda TBI uyarılması için kullanılan kemirgen modellerinde çoğunluğu kafa 5 (inceleme için 2 ye bakınız) veya çok az hareket izin verir. Burada özetlenen modeli, öznenin baş ve vücuda hızlanma / yavaşlama kuvvetleri uygular bir 180 ° dönme ve serbest düşme eşlik fiziksel sınırsız çocuk sıçan kafasına bir yüksek hız etkisini sunar. TBurada HTBH uyarılması için bu modifiye kilo damla tekniği ile ilişkili iki ana avantajı vardır. İlk model (davranışsal sonuçlar 6 bakınız tam açıklaması için) beyne herhangi bir açık zarar vermeden semptomolojisine gibi klinik olarak anlamlı sarsıcı üretir. Post-sarsıcı sendromun klinik raporları ile de tutarlı, bu modifiye kilo bırak tekniği heterojen sonuçlar üretir. HTBH gelen etkileri önemli olmasına rağmen, birden fazla sonuç ölçütleri üzerinde incelendiğinde bir HTBH deneyimli kemirgenler arasında önemli farklılıklar vardır. İkinci olarak, yöntem tekrar HTBH 7 çalışmasına izin verir. Mevcut TBI modellerin çoğunluğu gibi ciddi yaralanmalara indirebilmek gibi, tüm korteks kapsamlı zarar vermeden tekrarlayan TBI incelemek için genellikle ikinci hasara yol zor ve neredeyse imkansız. Bu nedenle, sanayii için modifiye kilo damla tekniğini kullanarak birincil gerekçesiHTBH ve ction daha yakından çocuk toplumlarda patofizyoloji ve sarsıntının semptomolojiyi ve tekrarlayan TBI temsil eden bir yaralanma üretmektir. Özellikle çocukluk döneminde artan sporla ilgili HTBH insidansı, düşme ve kazaları otomobil ile, HTBH bu eşsiz kemirgen modeli kolaylıkla çoklu-hit uygulanabilir sarsıcı gibi beyin hasarının çalışma için değerli bir araç ile araştırmacılar sağlar paradigmalar.

<table border="0" cellpadding="0" cellspacing="0" width="824">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Brass Weights</td>
			<td style="width:155px;">Ginsberg Scientific</td>
			<td style="width:187px;">7-2500-2</td>
			<td style="width:219px;">Need to have metal loop attached to base</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Alluminum Foil</td>
			<td style="width:155px;">Alcan</td>
			<td style="width:187px;"></td>
			<td>Available at most grocery stores</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Masking Tape</td>
			<td style="width:155px;"></td>
			<td style="width:187px;"></td>
			<td>Commercially available&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">U-Shaped Plastic Stand</td>
			<td style="width:155px;"></td>
			<td style="width:187px;"></td>
			<td>Constructed by Laboratory</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Clamp Stand</td>
			<td style="width:155px;">Sigma-Aldrich</td>
			<td style="width:187px;">Z190357</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Plastic Guide Tube</td>
			<td style="width:155px;"></td>
			<td style="width:187px;"></td>
			<td>Could be constructed or purchased at a hardware store</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Fishing Line</td>
			<td style="width:155px;">Angler 10lb&#160;</td>
			<td style="width:187px;"></td>
			<td>Purchased from a sporting goods retailer&#160;</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:264px;">Isoflurane</td>
			<td style="width:155px;">Pharmaceutical Partners of Canada</td>
			<td style="width:187px;">DIN 02237518</td>
			<td>Inhalation Anesthetic</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Topical Lidocaine (30ml)</td>
			<td style="width:155px;">Astra Zeneca</td>
			<td style="width:187px;">DIN 0001694</td>
			<td>Xylocaine Jelly 2%&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Cotton Swabs</td>
			<td style="width:155px;"></td>
			<td style="width:187px;"></td>
			<td>Commercially available&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Heating Pad - 3 heat setting</td>
			<td style="width:155px;"></td>
			<td style="width:187px;"></td>
			<td>Commercially available&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Stop Watch</td>
			<td style="width:155px;">Sportline</td>
			<td style="width:187px;">L303</td>
			<td>Purchased from a sporting goods retailer&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Video Camera</td>
			<td style="width:155px;">Sony</td>
			<td style="width:187px;">HDR-CX260V</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:264px;">Sprague Dawley Rats</td>
			<td style="width:155px;">Charles River Laboratories</td>
			<td style="width:187px;">SAS SD 40</td>
			<td>Male and females ordered from Charles River Laboratories and pups bred in-house</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:264px;">Balance Beam</td>
			<td></td>
			<td></td>
			<td>Constructed by Laboratory</td>
		</tr>
	</tbody>
</table>

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.

Yukarıda açıklanan değiştirilmiş ağırlık-bırak tekniği çocuk sıçanlarda hafif travmatik beyin hasarı (HTBH) indüksiyonu için güvenilir bir yöntemdir. 150 g kadar bir darbe ağırlığı kullanarak, bu teknik, başarılı bir şekilde 50-120 g arasında değişir çocuk farelere uygulanmıştır. Buna ek olarak, yöntem kolayca tekrar HTBH çalışması için aynı hayvanlarda tekrar edilebilir. (Şekil 3), tek bir HTBH sergileyin zaman sağa bir artış tecrübe ve görünen hayvanlar uyanma üzerine hayrete rağmen, hızla normal faaliyetlerine devam ve sahte-yaralı hayvanlardan görsel ayırt edilemez. Yaralanma bakarak etkisi ile ilişkili herhangi bir ağrı ortadan kaldırır, topikal lidokain, gerekli tek analjezik hafif olduğunu göz önüne alındığında. Ağrı kesiciler tipik enflamatuar ve geri kazanım işlemlerine müdahale ettiği bilindiğinden, bu araştırma için önemlidir. Açık semptomolojisine eksikliği nedeniyle, kiriş yürüme görevi için güvenilir olduğunuHTBH uyarılmasını doğrulamak için kullanılabilir ol elde edilir. Bir HTBH deneyim değil tüm hayvanlar ışın yürüme görev açıklarının sergileyecek ki, dikkat etmek önemlidir, ama bir sahte yaralanma ile çocuk sıçanlara kıyasla bir grup olarak, bir HTBH ile çocuk fareler çok daha arka bacak ayak-fişleri göstermek (Şekil 4). Bu modifiye ağırlık bırak tekniği bir diğer önemli özelliği yaralanma indüksiyon sırasında çocuk sıçan uygulanan kısıtlama olmaması. Hızlı dönme hızlanma ve yavaşlama ardından kafasına bakarak darbe sunarak, bu model daha yakından HTBH ve sarsıntı atfedilen biyomekanik güçleri temsil eder. Bu prosedür çocuk veya yetişkin sıçanlarda farelere uygulandığında, mortalite oranları (7/202 çocuk hayvanlar ~ 3.4% ölüm oranı) son derece düşük olup, kafatası kırığı ve kafa içi kanama 6,7 derece nadirdir. Buna ek olarak, model, klinik açıdan ilişkili sy üretirmptomology. Tek bir HTBH deneyimli Çocuk kemirgenler depresif-benzeri davranışlar artan yönetici fonksiyonu açıkları, ve değişmiş sosyal etkileşimler 6,9 ile birlikte, denge ve motor davranışları açıkları gösterdi. Benzer şekilde, yetişkin fareler de zaman 7 kurtarmak hafif denge ve koordinasyon açıkları görüntüler. Son olarak, HTBH bu modeli kullanarak indüksiyon az anestezi gerektirir ve cerrahi hazırlık veya kafatası içine burrowing içermez. Sonuçlar, bu nedenle cerrahi veya anestezi ile tetiklenen karıştırıcı enflamatuar veya immünolojik etkileri ile önyargılı değil. Ayrıca, açık yaraların hızlı bir toparlanma süresi ve eksikliği kemirgenler HTBH deneyimi kısa bir süre sonra oluşacak ek test paradigmaları başladığını sağlar. <img alt="Şekil 1," fo:content-width="5in" src="/files/ftp_upload/51820/51820fig1highres.jpg" width="500" /> Şekil 1: </strong<html> &gt; Tüm ilgili boyutları ile plastik sahne ve tahsilat sünger U-şekilli. 10 cm bir mesafe toplama sünger ve çocuk sıçan sağlamak için plastik aşamasında üst arasında muhafaza edilmelidir C Artoon gösterimi 180&#39;e tamamlamak için yeterli zaman vardır ° dönme. <img alt="Şekil 2," fo:content-width="5in" src="/files/ftp_upload/51820/51820fig2highres.jpg" width="500" /> Şekil 2: Yaranın platformun (A) &#39;Fotografik temsili. Kafa düşen ağırlık altında doğrudan böylece çocuk sıçan attı kalay folyo göğüs aşağı yerleştirilir. yaralanma indüksiyon platformu (B) Yan görünümü. (C) HTBH indüksiyonunda kullanılan ağırlık Fotografik gösteri . yüklemek / 51.820 / 51820fig3highres.jpg &quot;width =&quot; 500 &quot;/&gt; Şekil 3: a. HTBH sergileyin önemli bir artış almış bir tek HTBH ve sahte yaralanma yaşadı çocuk sıçanlar (* p &lt;0.01) Rats deneyimli zaman sağa çocuk sıçanlarda arasındaki ortalama farklar grafiksel gösterimi zaman süresi sırtüstü pozisyonda kendilerini sağa gerekiyordu. <img alt="Şekil 4," fo:content-width="5in" src="/files/ftp_upload/51820/51820fig4highres.jpg" width="500" /> Şekil 4: Tek bir HTBH ve sahte yaralanma yaşadı çocuk sıçanlar (* p &lt;0.05) deneyimli çocuk fareler tarafından Kiriş Yürüyüş görev sergilenen arka bacak ayak-slip ortalama sayısının grafiksel gösterimi.

Watch this Scientific Journal Video about A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats at JoVE.com

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

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.

Çocuk Rats için Hafif Travmatik Beyin Hasarı Yeni Bir Model

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

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23.4K Görüntüleme.  University of Calgary. 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. 

Video: A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Acute and Chronic Tactile Sensory Testing after Spinal Cord Injury in Rats

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory testing in rat SCI models is needed. However, until recently, no single testing approach had been validated for SCI so that standardized methods have not been implemented across labs. Additionally, available testing methods could not be implemented acutely or when severe motor impairments existed, preventing studies of the development of SCI-induced allodynia3. Here we present two validated sensory testing methods using von Frey Hair (VFH) monofilaments which quantify changes in tactile sensory thresholds after SCI4-5. One test is the well-established Up-Down test which demonstrates high sensitivity and specificity across different SCI severities when tested chronically5. The other test is a newly-developed dorsal VFH test that can be applied acutely after SCI when allodynia develops, prior to motor recovery4-5. Each VFH monofilament applies a calibrated force when touched to the skin of the hind paw until it bends. In the up-down method, alternating VFHs of higher or lower forces are used on the plantar L5 dermatome to delineate flexor withdrawal thresholds. Successively higher forces are applied until withdrawal occurs then lower force VFHs are used until withdrawal ceases. The tactile threshold reflects the force required to elicit withdrawal in 50% of the stimuli. For the new test, each VFH is applied to the dorsal L5 dermatome of the paw while the rat is supported by the examiner. The VFH stimulation occurs in ascending order of force until at least 2 of 3 applications at a given force produces paw withdrawal. Tactile sensory threshold is the lowest force to elicit withdrawal 66% of the time. Acclimation, testing and scoring procedures are described. Aberrant trials that require a retest and typical trials are defined. Animal use was approved by Ohio State University Animal Care and Use Committee.

We describe two tactile sensory testing methods for acute or chronic periods of spinal cord injury in rats. These validated procedures can detect the development and maintenance of allodynia-like sensations.

Sıçanlarda Spinal Kord Yaralanma sonrası Akut ve Kronik Dokunsal Duyu Testi

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory ...

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A Contusion Model of Severe Spinal Cord Injury in Rats

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is described to obtain a consistent model of severe SCI. Use of a stereotactic frame and computer controlled impactor allows for creation of reproducible injury. Hypothermia and urinary tract infection pose significant challenges in the post-operative period. Careful monitoring of animals with daily weight recording and bladder expression allows for early detection of post-operative complications. The functional results of this contusion model are equivalent to transection models. The contusion model can be utilized to evaluate the efficacy of both neuroprotective and neuroregenerative approaches.

A contusion model of severe spinal cord injury is described. Detailed pre-operative, operative and post-operative steps are described to obtain a consistent model.

Sıçanlarda Şiddetli Spinal Kord Yaralanması bir bere modeli

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is ...

A Novel Vertebral Stabilization Method for Producing  Contusive Spinal Cord Injury

Clinically-relevant animal cervical spinal cord injury (SCI) models are essential for developing and testing potential therapies; however, producing reliable cervical SCI is difficult due to lack of satisfactory methods of vertebral stabilization. The conventional method to stabilize the spine is to suspend the rostral and caudal cervical spine via clamps attached to cervical spinous processes. &#160;However, this method of stabilization fails to prevent tissue yielding during the contusion as the cervical spinal processes are too short to be effectively secured by the clamps (Figure 1). &#160;Here we introduce a new method to completely stabilize the cervical vertebra at the same level of the impact injury. &#160;This method effectively minimizes movement of the spinal column at the site of impact, which greatly improves the production of consistent SCIs. &#160;We provide visual description of the equipment (Figure 2-4), methods, and a step-by-step protocol for the stabilization of the cervical 5 vertebra (C5) of adult rats, to perform laminectomy (Figure 5) and produce a contusive SCI thereafter. &#160;Although we only demonstrate a cervical hemi-contusion using the NYU/MASCIS impactor device, this vertebral stabilization technique can be applied to other regions of the spinal cord, or be adapted to other SCI devices. &#160;Improving spinal cord exposure and fixation through vertebral stabilization may be valuable for producing consistent and reliable injuries to the spinal cord. &#160;This vertebral stabilization method can also be used for stereotactic injections of cells and tracers, and for imaging using two-photon microscopy in various neurobiological studies.

Vertebral stabilization is necessary for minimizing variability, and for producing consistent experimental spinal cord injuries.&#160; Using a customized stabilizing apparatus in conjunction with the NYU/MASCIS impactor device, we have demonstrated here the proper equipment and procedure for generating reproducible hemi-contusive cervical (C5) spinal cord injuries in adult rats.

Kontuzif omurilik hasarın üretmek için Yeni Bir Omurga Stabilizasyon Yöntemi

Clinically-relevant animal cervical spinal cord injury (SCI) models are essential for developing and testing potential therapies; however, producing ...

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

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

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

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

Bir olarak beyin mikrovasküler endotel hücreleri (cend) olarak gerin<em&gt; In Vitro</emKan Beyin Bariyer&gt; Travmatik Beyin Hasarı Modeli

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

Controlled Cortical Impact Model for Traumatic Brain Injury

Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.

Traumatic brain injuries (TBIs) remain a serious health problem. Using the controlled cortical impact surgery model, research on the effects of TBI and possible treatment methods may be performed.

Travmatik Beyin Hasarı için Kontrollü Kortikal Etki Modeli

Every year over a million Americans suffer a traumatic brain injury (TBI).  Combined with the incidence of TBIs worldwide, the physical, emotional, ...

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

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

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

Renal İskemi Reperfüzyon Hasarı: Yaralanma Fare Modeli ve Rejenerasyon

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

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

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

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

Farelerde Doku Yerinden Olma Esaslı Taşan Spinal Kord Yaralanması Modeli

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

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.

Tek ve Tekrarlayan Hafif Travmatik Beyin Hasarı İçin Bir Fare Modeli

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 ...

Spinal Cord Lateral Hemisection and Asymmetric Behavioral Assessments in Adult Rats

Incomplete spinal cord injury (SCI) often leads to impairments of sensorimotor functions and is clinically the most frequent type of SCI. Human Brown-S&#233;quard syndrome&#160;is a common type of incomplete SCI caused by a lesion to one half of the spinal cord which results in paralysis and loss of&#160;proprioception&#160;on the same (or ipsilesional) side as the injury, and loss of pain and temperature sensation on the opposite (or contralesional) side. Adequate methodologies for producing a spinal cord lateral hemisection (HX) and assessing neurological impairments are essential to establish a reliable animal model of Brown-S&#233;quard syndrome. Although lateral hemisection model plays a pivotal role in basic and translational research, standardized protocols for creating such a hemisection and assessing unilateralized function are lacking. The goal of this study is to describe step-by-step procedures to produce a rat spinal lateral HX at the 9th thoracic (T9) vertebral level. We, then, describe a combined behavior scale for HX (CBS-HX) that provides a simple and sensitive assessment of asymmetric neurological performance for unilateral SCI. The CBS-HX, ranging from 0 to 18, is composed of 4 individual assessments which include unilateral hindlimb stepping (UHS), coupling, contact placing, and grid walking. For CBS-HX, the ipsilateral and contralateral hindlimbs are assessed separately. We found that, after a T9 HX, the ipsilateral hindlimb showed impaired behavior function whereas the contralateral hindlimb showed substantial recovery. The CBS-HX effectively discriminated behavioral functions between ipsilateral and contralateral hindlimbs and detected temporal progression of recovery of the ipsilateral hindlimb. The CBS-HX components can be analyzed separately or in combination with other measures when needed. Although we only provided visual descriptions of the surgical procedures and behavioral assessments of a thoracic HX, the principle may be applied to other incomplete SCIs and at other levels of the injury.

Here we describe surgical procedures to produce a reliable spinal cord lateral hemisection (HX) at the 9th thoracic level in adult rats and neurobehavioral assessments designed for detecting asymmetric deficits after such a unilateral injury.

Erişkin Sıçanlarda Spinal Kord Lateral Hemisite ve Asimetrik Davranış Değerlendirmeleri

Incomplete spinal cord injury (SCI) often leads to impairments of sensorimotor functions and is clinically the most frequent type of SCI. Human ...

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of disorders of consciousness, disrupted higher brain function, and verbal disturbances. As a consequence of an insufficient ability to communicate, objective evaluations are needed from family members, medical staff, and caregivers. One such evaluation is the assessment of functioning brain areas. Recently, multimodal brain imaging has been used to explore the function of damaged brain areas. [18F]-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG-PET/CT) is a successful tool for examining brain function. However, the assessment of brain glucose metabolism based on [18F]FDG-PET/CT is not standardized and depends on several varying parameters, as well as the patient&#39;s condition. Here, we describe a series of semiquantitative assessment protocols for a region-of-interest (ROI) image analysis using self-produced [18F]FDG tracers in patients with sTBI. The protocol focuses on screening the participants, preparing the [18F]FDG tracer in the hot lab, scheduling the acquisition of [18F]FDG-PET/CT brain images, and measuring glucose metabolism using the ROI analysis from a targeted brain area.

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography is useful for studying glucose metabolism related to brain function. Here, we present a protocol for an [18F]FDG tracer set-up and semiquantitative assessment of the region-of-interest analysis for targeted brain areas associated with clinical manifestations in patients with severe traumatic brain injury.

Yarı kantitatif değerlendirmesi ağır beyin hasarı olan hastalarda [18F] FDG izleyici kullanarak

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of ...