Bu çalışma Indiana Omurilik ve Beyin Hasarı Araştırma Hibeler (SCBI 200-12) fon tarafından desteklenen, Ralph W. ve Grace M. Showalter Araştırma Ödülü, Indiana Üniversitesi Biyolojik Araştırma Grant, NIH hibe RR025761 ve 1R21NS072631-01A.

Hayvan Bakımı Erkek C57 BL / 6 fareleri, grup yer alır ve yiyecek ve su ad libitum erişmek için serbest olan bir 12/12 saat ışık / karanlık döngüsünde tutuldu. Bu protokolde kullanılan hayvanlar 10-12 haftalık oldular. Tüm prosedürler Indiana Üniversitesi Hayvan Bakım ve Kullanım Kurulu tarafından onaylanan protokoller altında yapıldı. 1.. Cerrahi Hazırlık <ol><li> Bir ketamin / ksilazin karışımı (87.7 mg / ml Ketamin ve 12.3 mg / ml Ksilazin) kullanılarak fare anestezisi ve IP enjeksiyon yoluyla (1 ml / kg) uygulanması. </li><li> Kulakları arasındaki fare başını tıraş. </li><li> Ameliyat sırasında kurumasını önlemek için fare gözlerine petrol bazlı bir jöle uygulanır. </li><li> % 10 iyot ile traşlı bölgeyi temizleyin. Sonra iyot temizlemek için% 70 etanol kullanımı. </li><li> Kulak çubukları ve lokma plaka kullanılarak stereotaktik çerçeve içinde fare kafasını düzeltin. Beyin kararlı olduğundan emin olun. </li></ol> 2. Kranyektomi </p&gt; <ol><li> Makas ile baş ortasında uzunlamasına bir kesi olun. Sol tarafında kapalı cilt tutmak için bir hemostat kullanın. </li><li> Kafatası açığa çıkarmak için kemik üzerindeki kan ve doku kaldırmak için bir pamuk uçlu bir aplikatör kullanın. Maruz kafatası 1 dakika kurumasını bekleyin. </li><li> Baskı uygulamak ve kafatası hareketsiz kalmasını sağlamak için forseps kullanın. Anatomik Simgesel Lambda (kaudal yönü) ve bregmaya (frontal yönü) belirleyin. 4 mm çapında ve uzak orta hat 0.5 mm ve Lambda bregma merkezinde bir daire çizin. </li><li> Işaretli daire boyunca kesmek için bir matkap kullanın. Nazikçe kemik tozları üflemek. Dura mater zarar görmesini önlemek için kemik yoluyla tamamen delmek yok. </li><li> Kemiği kaldırmak ve dura mater maruz forseps kullanın. </li></ol> 3. Impaction Darbe sistem etkisi parametrelerini ayarlamak için bir kontrol kutusu, çarpmasının gerçekleştirmek için bir çalıştırıcı ve hareket güvenli bir stereotaktik çerçeve içeriretki için uator ve fare kafası. <ol><li> Ameliyat öncesi 3 m / sn &#39;ye aktüatörün hızım önceden ayarlanmıştır. </li><li> Farklı bir yaralanma ciddiyetinin uyarılması için farklı deformasyon derinliği önceden ayarlanmıştır. 0,0-0,2 mm, 0.5-1.0 mm ve 1,2-2,0 mm deformasyon derinlikleri sırasıyla, hafif, orta ve ağır TBIs neden olacaktır. Bu protokol, 3 m / sn hızı ile 1 mm bir deformasyon derinliğe sahip bir orta şiddetli beyin hasarı ulaşmak için nasıl açıkladı. </li><li> Stereotaktik çerçeve içinde sahibine Aktuatörü takın ve açık kafatası alanının merkezinde aktüatör (3 mm çapında) yuvarlak, yassı ucu sabitlemek için hareket mikromanipülatörler kullanın. Daha sonra darbe yeri yüzeyine bir açı paralel ucu ayarlayın. </li><li> Ucu darbe sitenin yüzeyine değene kadar uzanan modelinde aktüatörünü aşağı hareket ettirerek sıfır noktası kurmak. Sonra sıfıra stereotaktik kontrol panelindeki Z kanalını ayarlayın. </li><li> Çarpma ucu geri çekinAynı anda 1 mm aşağı aktüatörünü hareket ederken. </li><li> Yara bölgesi vurur ve 1 mm&#39;lik bir deformasyon derinliği elde etmek için etki düğmesine basın. </li></ol> 4. Yaralanma Sitesi Kapanış <ol><li> Herhangi bir kan aşağıdaki etkisini kaldırmak için pamuk uçlu aplikatörler kullanın, ancak yaralanma alana dokunmayın. </li><li> Vücut ısısını korumak için sıcak bir pad üzerinde fare yerleştirin. </li><li> Kanama durduktan sonra, kapalı yara sütür. Temiz bir kafes içine geri hayvan koyun ve sıcak ped gecede ameliyat kurtarmak için izin verir. </li><li> Yönetme Buprenorfin 0.05-0.10 mg / kg SQ ameliyattan sonra 2 gün boyunca her 8-12 saat. </li></ol>

<ol><li>Menon, D. K., Schwab, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Position+statement%3A+definition+of+traumatic+brain+injury%5BTitle%5D)+AND+%22Arch+Phys+Med+Rehabil%22%5BJournal%5D)">Position statement: definition of traumatic brain injury.</a> Arch Phys Med Rehabil. 91 (11), 1637-1640 (2010).</li>
<li>Lighthall, J. W., Dixon, C. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Experimental+models+of+brain+injury%5BTitle%5D)+AND+%22J+Neurotrauma%22%5BJournal%5D)">Experimental models of brain injury.</a> J Neurotrauma. 6 (2), 83-97 (1989).</li>
<li>Dixon, C. E., Clfton, G. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+controlled+cortical+impact+model+of+traumatic+brain+injury+in+the+rat%5BTitle%5D)+AND+%22J+Neurosci+Methods%22%5BJournal%5D)">A controlled cortical impact model of traumatic brain injury in the rat.</a> J Neurosci Methods. 39 (3), 253-262 (1991).</li>
<li>Scheff, S. W., Baldwin, S. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Morris+water+maze+deficits+in+rats+following+traumatic+brain+injury%3A+lateral+controlled+cortical+impact%5BTitle%5D)+AND+%22J+Neurotrauma%22%5BJournal%5D)">Morris water maze deficits in rats following traumatic brain injury: lateral controlled cortical impact.</a> J Neurotrauma. 14 (9), 615-627 (1997).</li>
<li>Smith, D. H., Soares, H. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+model+of+parasagittal+controlled+cortical+impact+in+the+mouse%3A+cognitive+and+histopathologic+effects%5BTitle%5D)+AND+%22J+Neurotrauma%22%5BJournal%5D)">A model of parasagittal controlled cortical impact in the mouse: cognitive and histopathologic effects.</a> J Neurotrauma. 12 (2), 169-178 (1995).</li>
<li>Hannay, H. J., Feldman, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Validation+of+a+controlled+cortical+impact+model+of+head+injury+in+mice%5BTitle%5D)+AND+%22J+Neurotrauma%22%5BJournal%5D)">Validation of a controlled cortical impact model of head injury in mice.</a> J Neurotrauma. 16 (11), 1103-1114 (1999).</li>
<li>Natale, J. E., Ahmed, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Gene+expression+profile+changes+are+commonly+modulated+across+models+and+species+after+traumatic+brain+injury%5BTitle%5D)+AND+%22J+Neurotrauma%22%5BJournal%5D)">Gene expression profile changes are commonly modulated across models and species after traumatic brain injury.</a> J Neurotrauma. 20 (10), 907-927 (2003).</li>
<li>Anderson, R. W., Brown, C. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Impact+mechanics+and+axonal+injury+in+a+sheep+model%5BTitle%5D)+AND+%22J+Neurotrauma%22%5BJournal%5D)">Impact mechanics and axonal injury in a sheep model.</a> J Neurotrauma. 20 (10), 961-974 (2003).</li>
<li>Lighthall, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Controlled+cortical+impact%3A+a+new+experimental+brain+injury+model%5BTitle%5D)+AND+%22J+Neurotrauma%22%5BJournal%5D)">Controlled cortical impact: a new experimental brain injury model.</a> J Neurotrauma. 5 (1), 1-15 (1988).</li>
<li>Chen, S., Pickard, J. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Time+course+of+cellular+pathology+after+controlled+cortical+impact+injury%5BTitle%5D)+AND+%22Exp+Neurol%22%5BJournal%5D)">Time course of cellular pathology after controlled cortical impact injury.</a> Exp Neurol. 182 (1), 87-102 (2003).</li>
<li>Long, J. B., Bentley, T. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Blast+overpressure+in+rats%3A+recreating+a+battlefield+injury+in+the+laboratory%5BTitle%5D)+AND+%22J+Neurotrauma%22%5BJournal%5D)">Blast overpressure in rats: recreating a battlefield injury in the laboratory.</a> J Neurotrauma. 26 (6), 827-840 (2009).</li>
<li>Clark, R. S., Schiding, J. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Neutrophil+accumulation+after+traumatic+brain+injury+in+rats%3A+comparison+of+weight+drop+and+controlled+cortical+impact+models%5BTitle%5D)+AND+%22J+Neurotrauma%22%5BJournal%5D)">Neutrophil accumulation after traumatic brain injury in rats: comparison of weight drop and controlled cortical impact models.</a> J Neurotrauma. 11 (5), 499-506 (1994).</li>
<li>Werner, C., Engelhard, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Pathophysiology+of+traumatic+brain+injury%5BTitle%5D)+AND+%22Br+J+Anaesth%22%5BJournal%5D)">Pathophysiology of traumatic brain injury.</a> Br J Anaesth. 99 (1), 4-9 (2007).</li>
<li>Colicos, M. A., Dixon, C. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Delayed%2C+selective+neuronal+death+following+experimental+cortical+impact+injury+in+rats%3A+possible+role+in+memory+deficits%5BTitle%5D)+AND+%22Brain+Res%22%5BJournal%5D)">Delayed, selective neuronal death following experimental cortical impact injury in rats: possible role in memory deficits.</a> Brain Res. 739 (1-2), 111-119 (1996).</li>
<li>Raghavendra Rao, V. L., Dogan, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Traumatic+brain+injury+leads+to+increased+expression+of+peripheral-type+benzodiazepine+receptors%2C+neuronal+death%2C+and+activation+of+astrocytes+and+microglia+in+rat+thalamus%5BTitle%5D)+AND+%22Exp+Neurol%22%5BJournal%5D)">Traumatic brain injury leads to increased expression of peripheral-type benzodiazepine receptors, neuronal death, and activation of astrocytes and microglia in rat thalamus.</a> Exp Neurol. 161 (1), 102-114 (2000).</li>
<li>Gao, X., Chen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Moderate+traumatic+brain+injury+promotes+neural+precursor+proliferation+without+increasing+neurogenesis+in+the+adult+hippocampus%5BTitle%5D)+AND+%22Exp+Neurol%22%5BJournal%5D)">Moderate traumatic brain injury promotes neural precursor proliferation without increasing neurogenesis in the adult hippocampus.</a> Exp Neurol. 239, 38-48 (2013).</li>
</ol>

The authors have nothing to disclose.

Başarılı bir CCI neden olmak için bir elektronik mıknatıs etki sistemi ile tutarlı TBIs üretilmesi için en önemli adımlar şunlardır: 1) sabit bir şekilde stereotaktik çerçeve içinde fare baş sabitlenmesi; 2) fareler arasında kemik penceresinin aynı boyut ve kraniektomi üretilmesi sırasında bunun altında dura zarar vermeden kemik çıkarılması; 3) doğru açık alanın merkezinde darbe ucu konumlandırılması ve çarpmadan önce sıfır noktasını tesis. Bir fare k...

Travmatik beyin hasarı (TBI) bir beyin fonksiyonlarında değişiklik, ya da bir dış kuvvet 1 kaynaklanan beyin patoloji diğer delil olarak tanımlanır. TBIs özellikle Amerika Birleşik Devletleri&#39;nde ve dünya çapında önemli bir sağlık sorunu olmaya devam etmektedir. Hastalık Kontrol ve Önleme Merkezlerine göre, en az 1.7 milyon TBIs bütün yaralanmalı bağlı ölümlerin% 30.5 sonuçlanan Birleşik Devletleri&#39;nde yılda meydana gelir. 2000 yılında, doğrudan tıbbi maliyetleri ve TBIs dolaylı maliyetler tek başına ABD&#39;de tahmini 76500000000 $ olarak gerçekleşti. Önceki yıllarda teknolojik gelişmeler ve tedavi TBIs muzdarip olanlar için yaşam kalitesini ve uzunluğunu geliştirilmiş olmasına rağmen, etkili bir ilaç veya koruyucu tedaviler şu anda mevcut. Nedeniyle karmaşıklığı ve doku lezyonları, hücre ölümü ve akson dejenerasyon da dahil olmak üzere TBIs, geniş kapsamlı etkileri, herhangi bir iki yaralanma aynıdır; Böylece, hayvanlar için hiçbir geçerli TBI modeli doğru üretirTBI tüm yönleri olarak insanlarda görülen. Ancak, hayvan modelleri daha TBIs klinik belirtilerini anlamak umuduyla TBI çeşitli etkilerini araştırmak için gerekli hemen hemen aynı yaralanmaları üretme yeteneği sağlarlar. Kontrol kortikal darbe (CCI) modeli bir hayvanın maruz dura fiziksel etki sunmak için bir darbe sistemi kullanır. Bu hafif insanlar tarafından hissedilen şiddetli benzer değişen TBIs uyarmaktadır. Bu yaralanma ilk olarak gelincik 2 özelliği ve daha sonra 3,4-sıçan, fare 5-7 ve koyun 8 kullanılmak üzere uyarlanmıştır. İlk nitelenmesi, yaralanma site orta hat 2,9 ve lateral kortekse 10 üzerinden hem yerleştirildi. CCI TBIs için ve potansiyel etkisini araştıran tedavi kolay ve doğru bir metot sağlar. CCİ modeli, sıvı perküsyon ve ağırlık düşümüne ilave olarak modelleri işbirliği vardırmmonly TBIs üretmek için kullanılır. Ancak, bu modeller daha az yaralanma parametreleri üzerinde kontrol, insan TBIs görmedim eden histopatolojik değişiklikleri üreten, ve farelerde 3,5,10 kazayla ölüm insidans dahil mevcut sınırlamalar,. Patlama dalgası modeli aynı TBIs üretmek için kullanılır. Patlama dalgası modeli mekanik etkisi aşağıdaki görülmüştür eden histopatolojik değişiklikleri yeniden olmamasına rağmen, bu modeli doğru özellikle askeri personel 11 deneyimli TBIs üretiyor. Kontrollü kortikal etki modeli nedeniyle, zaman, hız ve etki 5 derinliği olarak deformasyon parametreleri üzerinde tam kontrolü için kontrol etmek kolaydır. Böyle bir doğruluk daha uygulanabilir bütün bir hayvan grubunun genelinde yaklaşık aynı yaralanmaları kopyalayan yapar. En önemlisi, CCI insan TBIs 12 görülen özelliklere sahip TBIs üretir. Ancak, patolojik chan tam spektrum üreyen tümüyle başarılı tek bir hayvan modeli vardırTBI sonrası gözlenen Ges. Daha fazla araştırma tamamen TBI sonra meydana akut ve kronik değişiklikleri ortaya çıkarmak için gereklidir. Birincil ve ikincil yaralanmalar: yaralanmaları iki tip bir TBI sonrasında görülmektedir. Birincil yaralanma çarpma anında meydana gelir ve terapötik tedaviler duyarlı değildir; Ancak, ilk hasardan sonra devam ikincil yaralanmalar tedavilere 13 tabidir. Kontrollü kortikal etki modeli böylece araştırmacılar ikincil yaralanma potansiyel uzun süreli etkileri için TBI etkilerini ve potansiyel terapötik tedavileri araştırmak için izin, birincil yaralanma üretir. CCI modelini kullanarak potansiyel araştırma alanları nöronal ölüm, serebral ödem, nöron, vasküler etkileri, eden histopatolojik değişiklikleri ve hafıza açıkları ve 3,13-16 daha fazlasını içerir.

<table><tbody><tr><td>Povidone-iodine 7.5%</td><td>Purdue product L.P.</td><td></td><td>Surgical scrub</td></tr><tr><td>Cotton tipped applicators</td><td>Henry Schein</td><td>100-6015</td><td>Remove blood and debris</td></tr><tr><td>Scissor</td><td>Fine Science Tools</td><td>14084-08</td><td>Surgery</td></tr><tr><td>Forcept</td><td>Fine Science Tools</td><td>11293-00</td><td>Surgery</td></tr><tr><td>Hemostat</td><td>Fine Science Tools</td><td>13021-12</td><td>Surgery</td></tr><tr><td>Rechargeable Cordless Micro Drill</td><td>Stoelting</td><td>58610</td><td>Combine with Burrs for generating the bone window</td></tr><tr><td>Burrs for Micro Drill</td><td>Fine Science Tools</td><td>19007-05</td><td></td></tr><tr><td>Suture monofilament</td><td>Ethicon</td><td>G697</td><td>Suture</td></tr><tr><td>tert-Amyl alcohol</td><td>Sigma</td><td>152463-250ML</td><td>Making 2.5% Avertin</td></tr><tr><td>2,2,2-Tribromoethanol</td><td>Sigma</td><td>T48402-25G</td><td>Making 2.5% Avertin</td></tr></tbody></table>

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.

Kontrollü kortikal etki modeli hafif şiddetli şiddeti arasında değişen TBIs üretir. Post-darbe kafatası şişme miktarı, kanama, ve darbe yerinde kranial bozulma hızı ve deformasyon derinliği parametreleri kaynaklanan yaralanma şiddetinin ortaya çıkaracaktır. Hafif TBIs nedeniyle sınırlı dura ihlali darbe site ve hafif kanama da kranial şişmesine neden. Bir orta TBI kranial şişme sergiler nedeniyle impaksiyon üzerine dura ihlali (Şekil 1) artmış kanama. Orta ve şiddetli TBI a...

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

Controlled Cortical Impact Model for Traumatic Brain Injury

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

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, ...

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

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

28.5K Görüntüleme.  Indiana University School of Medicine. Traumatic brain injuries (TBIs) remain a serious health problem. Using the controlled cortical impact surgery model, research on the effects of TBI and possible treatment methods may be performed.

Video: Controlled Cortical Impact Model for Traumatic Brain Injury

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

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

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

Insan kaynaklı pluripotent kök hücre türetilen nöral hücrelerin terapötik transplantasyonu ile fare beyin yaralanması kontrollü Kortiik darbe modeli

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

Gelişim Biyolojisi

A Repetitive Concussive Head Injury Model in Mice

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

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

Farelerde Bir Tekrarlanan Concussive Kafa Travması Modeli

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

Tıp

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 ...

Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the United States. In fact, TBI is a contributing factor to over a third of all injury-related mortality. Nonetheless, the cellular and molecular mechanisms underlying the pathophysiology of TBI are poorly understood. Thus, preclinical models of TBI capable of replicating the injury mechanisms pertinent to TBI in human patients are a critical research need. The controlled cortical impact (CCI) model of TBI utilizes a mechanical device to directly impact the exposed cortex. While no model can full recapitulate the disparate injury patterns and heterogeneous nature of TBI in human patients, CCI is capable of inducing a wide range of clinically applicable TBI. Furthermore, CCI is easily standardized allowing investigators to compare results across experiments as well as across investigative groups. The following protocol is a detailed description of applying a severe CCI with a commercially available impacting device in a murine model of TBI.

Here we describe a protocol for the induction of murine traumatic brain injury via an open-head controlled cortical impact.

Travmatik Beyin Hasarı İndüksiyonu için Kontrollü Kortikal Etki Murine Modeli

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the ...

Nörobilim

Low-intensity Blast Wave Model for Preclinical Assessment of Closed-head Mild Traumatic Brain Injury in Rodents

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of medical visits in the United States. There are currently no FDA-approved treatments available for TBI. The increased incidence of military-related, blast-induced TBI further accentuates the urgent need for effective TBI treatments. Therefore, new preclinical TBI animal models that recapitulate aspects of human blast-related TBI will greatly advance the research efforts into the neurobiological and pathophysiological processes underlying mild to moderate TBI as well as the development of novel therapeutic strategies for TBI.
Here we present a reliable, reproducible model for the investigation of the molecular, cellular, and behavioral effects of mild to moderate blast-induced TBI. We describe a step-by-step protocol for closed-head, blast-induced mild TBI in rodents using a bench-top setup consisting of a gas-driven shock tube equipped with piezoelectric pressure sensors to ensure consistent test conditions. The benefits of the setup that we have established are its relative low-cost, ease of installation, ease of use and high-throughput capacity. Further advantages of this non-invasive TBI model include the scalability of the blast peak overpressure and the generation of controlled reproducible outcomes. The reproducibility and relevance of this TBI model has been evaluated in a number of downstream applications, including neurobiological, neuropathological, neurophysiological and behavioral analyses, supporting the use of this model for the characterization of processes underlying the etiology of mild to moderate TBI.

We present here a protocol of a blast wave model for rodents to investigate neurobiological and pathophysiological effects of mild to moderate traumatic brain injury. We established a gas-driven, bench-top setup equipped with pressure sensors allowing for reliable and reproducible generation of blast-induced mild to moderate traumatic brain injury.

Kemirgenlerde Kapalı Başlı Hafif Travmatik Beyin Hasarının Preklinik Değerlendirmesi için Düşük Yoğunluklu Patlama Dalgası Modeli

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of ...

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

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

<meta charset="utf8"></head><body>Travmatik Kanama, Konkontüzyon ve Nöroinflamasyon için Preklinik Kontrollü Kortikal Etki Modeli

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

Travmatik Kanama, Konkontüzyon ve Nöroinflamasyon için Preklinik Kontrollü Kortikal Etki Modeli

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

Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and understanding the mechanisms of how a TBI alters brain function. The availability of multiple animal models of TBI is necessary to model the different aspects and severities of TBI seen in people. This manuscript describes the use of a midline closed head injury (CHI) to develop a mouse model of mild TBI. The model is considered mild because it does not produce structural brain lesions based on neuroimaging or gross neuronal loss. However, a single impact creates enough pathology that cognitive impairment is measurable at least 1 month after injury. A step-by-step protocol to induce a CHI in mice using a stereotaxically guided electromagnetic impactor is defined in the paper. The benefits of the mild midline CHI model include the reproducibility of the injury-induced changes with low mortality. The model has been temporally characterized up to 1 year after the injury for neuroimaging, neurochemical, neuropathological, and behavioral changes. The model is complementary to open skull models of controlled cortical impact using the same impactor device. Thus, labs can model both mild diffuse TBI and focal moderate-to-severe TBI with the same impactor.

The protocol describes mild traumatic brain injury in a mouse model. In particular, a step-by-step protocol to induce a mild midline closed head injury and the characterization of the animal model is fully explained.

Farelerde Hafif Travmatik Beyin Hasarının Elektromanyetik Kontrollü Kapalı Kafa Modeli

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and ...

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

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

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

Hafif Travmatik Beyin Hasarının Uyanık Kapalı Kafa Travması Modelini Kullanarak Sinaptik Plastisitedeki Değişikliklerin Değerlendirilmesi

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

Kapalı Kafa Travması Yöntemiyle Farelerde rmTBI İndüksiyonu

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

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

Yazar Spotlight: Tekrarlanan Hafif Travmatik Beyin Hasarında Mekanizmaların ve Rehabilitasyonun Araştırılması için Kemirgen Modellerinin Optimize Edilmesi

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

İnceltilmiş kafatası penceresi ve sıvı perküsyonu içeren tekrarlayan hafif travmatik beyin hasarının modifiye edilmiş fare modeli

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

Travmatik Beyin Hasarı için Kontrollü Kortikal Etki Modeli

Özet

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