Name: a repetitive concussive head injury model in mice
Uploaded: 2016-10-12T14:00:00.000+00:00
Duration: 5 min 42 s
Description: Watch this Scientific Journal Video about A Repetitive Concussive Head Injury Model in Mice at JoVE.com

This works was supported by funding from a Florida Health grant (Brain and spinal cord injury research fund) (KKW).

Tüm işlemler Florida Üniversitesi Kurumsal Hayvan Bakım ve Kullanım Kurulu tarafından ve Laboratuvar Hayvanları Bakım ve Kullanım Sağlık Rehberi National Institutes göre onaylanan protokoller # 201207692 altında gerçekleştirildi. 1. Hayvan Bakımı <ol><li> 3-4 aylık erkek C57BL / 6J fareler kullanın. Yatak, yuvalama malzeme, yiyecek ve su ad libitum sağlamak. Sabit 12 saat ışık / 12 saat karanlık döngüsü ile 22 ° C - 20 kontrol edilen ortam sıcaklıklarında fareler tutun. </li></ol> 2. Ön impaksiyon Hazırlık <ol><li> Elektromanyetik stereotaksik darbe cihazına ısmarlama silikon kauçuk kaplı metal ucu takın. Ucunun düz tabanlı prob ucu (Şekil 1A) yüzeyine paralel olduğundan emin olun. </li><li> % 2.5 izofluran bakım anestezi ardından% 4 izofluran ile fare anestezisi. debimetre aracılığıyla anestezi kontrol edin. monitor hayvan kadar anestezi seviyesi pedalı geri çekme refleksi kaybı göstererek anestezi cerrahi düzeyine ulaşır. </li><li> bir ısıtma yastığı üzerinde yüzükoyun pozisyonda fare koyun. Anestezi altında fare tutmak için bir huni şeklinde bir burun konisi kullanın. Tamamen bir düzeltici kullanarak tıraş. anestezi altında iken kuruluğunu önlemek için farenin gözleri vazelin oftalmik merhem kullanın. </li></ol> 3. Etki Parametreleri Ayar NOT: Etki sistemi darbe parametrelerini ayarlamak için bir kontrol kutusu, impaction gerçekleştirmek için bir aktüatör ve 3-hareket eksenleri ile bir dijital stereotaktik çerçeve içerir. <ol><li> 4 m / sn darbe cihazın hızını önceden ayarlanmış ve kontrol kutusu üzerinde 240 msn bekleme süresi. </li></ol> 4. Konumlandırma Darbe Merkezi <ol><li> 39 ° C&#39;ye yakın vücut ısısını korumak için hayvanın vücudunun altında yumuşak bir ısıtma yastığı koyun. Bir pron bir stereotaktik çerçeve içinde fare montekünt uç kulak çubukları ile e konumu. </li><li> Z-sürücü hareket ettirerek farenin kafasına yakın darbe ucu indirin. Hedef sagital sütür üzerinde koordinatları ortada X- ve Y-sürücüleri hareket ettirerek düz darbe ucu (9 mm çapında) ayarlayın. </li><li> Dikey iki kulak (Şekil 1C) arasında çizilen hayali bir yatay çizgi paralel olan darbe ucunun emin bir kenarı olun. etkinin merkezi (0 mm, yanal 4.5 mm kulaklararası için interaural 9 mm) interfrontal ve lambdoidea&#39;nın sütürler arasındaki merkezi sagital sütür yarıda karşılık gelir. </li></ol> 5. Darbe Derinlik Ayarı <ol><li> doğru etki derinliğini ayarlamak için, yalıtımlı silikon kauçuk kaplı darbe ucu yerine ek prob ucunu kullanın. </li><li> ipuçları geçmeden önce sıfıra dijital stereotaksik kontrol panelindeki X ve Y kanalı ayarlamak anahtarlama ipuçları sonra darbe merkezinin herhangi bir kayma var olduğundan emin olmak için. </li><li> prob taşıEl X ve Y-sürücüleri hareket ettirerek darbe alanının merkezine e ucu. </li><li> farenin kuyruk klibi temas sensörü. </li><li> prob ucu darbe sitenin yüzeyine temas edene kadar aşağı impaktörü (Z sürücü) taşıyın. </li><li> sıfıra stereotaksik kontrol panelindeki Z kanalını ayarlayın. </li><li> elle X ve Y sürücüleri kadar X- ve Y-sürücüleri (NOT dijital stereotaksik kontrol panelinde sıfır düğmeleri) ayarlayarak geri etki alanının darbe ucu taşı (darbe ucu daha önce yerleştirildi) sıfırdır. </li><li> kontrol kutusu üzerindeki geri çekme anahtarı hareket ettirerek çalıştırıcıyı geri çekin. El ile 4 mm aşağı impaktörü (Z sürücüsü) hareket ettirin. </li></ol> 6. Darbe <ol><li> kontrol kutusu üzerindeki etkisi anahtarını tıklayarak etkiyi tetikleyebilir ve 4 mm deformasyon derinliği elde. </li></ol> 7. Sonrası impaksiyon <ol><li> farenin ilk nefes bir zamanlayıcı kullanarak kadar etkisinden zamanı ölçmek. </li><li&gt; Enstrüman hayvan çıkarın ve vücut ısısını korumak için sıcak bir ped üzerine koyun. sternal yatma korumak için yeterli bilinci yerine kadar sahipsiz hayvan bırakmayın. </li><li> Temiz bir kafes içine geri hayvan dönmeden önce kurtarma için izin verin. Tamamen iyileşene kadar diğer hayvanların şirkete bir hayvan iade etmeyin. </li><li> Gözlemleyin ve günlük fareler tartmak. Fareler ağrı belirtileri varsa, intraperitoneal 1 de Meloksikamın ile enjekte - 24 saat - 2 mg / her 12 kg. </li></ol> 8. Tekrarlanan Gömülü <ol><li> gün 4, 7 farelere ek yaralanmaları verin ve ilk yaralanma (etkileri arasındaki 72 saat aralığı) sonra 10. </li></ol> 9. İmmunohistokimya (İHK) <ol><li> transcardial perfüzyon <ol><li> 200 m / kg pentobarbital intraperitonal enjeksiyon yoluyla fareler anestezi. </li><li> Değerlendirmek ve bir ayak tutam cerrahi düzlem anestezi sağlamak. saniyeure hafifçe kimyasal davlumbaz içine plastik bir çalışma yüzeyine forepaws ve arka pençeleri bantlama ile yatar pozisyonda fare. </li><li> Sadece klavikulaya kılıç şeklinde bir süreç altından göğüs orta hat boyunca deri yoluyla bir kesi yapmak. kılıç şeklinde bir süreç iki ek cilt kesiler yapmak ve yanal ventral göğüs kafesi tabanı boyunca devam edin. </li><li> göğüs boşluğu açın ve göğüs kaslarının ve göğüs kafesi üzerinden keserek kalp maruz. </li><li> künt forseps ile kalpte sabitleyin ve 1 yapmak - sol ventrikül 2 mm kesi. </li><li> Hemen sağ atrium içine kelebek iğne takın. yavaş yavaş şırınga iterek 20ml tuzlu su infüzyon başlayın. </li><li> tuzlu dan% 4 paraformaldehid geçin. paraformaldehit 20ml ile perfüzyon devam edin. </li><li> fare başını kesmek ve makasla cilt kaldırmak. Bir kemik kesici kullanarak kafatası beyin izole edin. </li></ol></li><li> Ckesit ryostat <ol><li> -80 ° C&#39;de optimum kesme sıcaklığı (OKT) formülasyonu ve donma embed beyin dokuları. sagital yönde kriyostat beyin yerleştirin. Kes beyin kesitleri 5 mikron kalınlığında. </li></ol></li><li> boyanma <ol><li> 1 saat süre ile, oda sıcaklığında dondurulmuş bölümler kurutun. </li><li> Oda sıcaklığında 1 saat için fosfat tamponlu tuzlu suda 100% 2 keçi serumu ul ve% 0.1 Triton X-100 (PBS) ile slaytlar inkübe edin. </li><li> PBS 300 ul slaytlar 3 kere yıkayın. 4 ° C&#39;de gece boyunca ayrı (200 1) ya da anti-ferritin antikor sonra anti-GFAP (200 1) ile slaytlar kuluçkalayın. </li><li> PBS 300 ul slaytlar 3 kere yıkayın. Daha sonra biyotin-konjuge sekonder antikor ile oda sıcaklığında 2 st için slaytlar inkübe edin. </li><li> PBS 300 ul slaytlar 3 kere yıkayın. Daha sonra 30 dakika boyunca oda sıcaklığında avidin-biyotin kompleksi (ABC) solüsyonu (1:50) ile slaytlar kuluçkalayın. </li><li>PBS 300 ul slaytlar 3 kere yıkayın. 8 dakika - sonra 3,3&#39;-diaminobenzidin 5 için (DAB) alt-tabaka çözeltisi (50 ml PBS, 10 ul H2O 2, 10 mg, DAB hap, kullanımdan önce filtre) &#39;de inkübe edilir. pozitif hücreler ortaya çıkıncaya kadar mikroskop altında slaytlar uyun. </li><li> 5 dakika boyunca yavaş çalışan musluk suyunda slaytlar durulayın. laboratuar silin bir ile temiz slaytlar. Sonra montaj orta ve lamel ile bölümleri monte edin. </li></ol></li></ol>

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The authors have no financial interest to disclose.

klinik durum morfolojik olarak benzer beyin yaralanmaları taklit etmek, post-sarsıntı belirtileri bekleniyor. Post-sarsıntı semptomlar genellikle baş ağrısı, baş dönmesi, baş dönmesi, yorgunluk, hafıza ve uyku problemleri, sorun konsantre yanı sıra anksiyete ve depresif ruh hali sayılabilir. somatik semptomlar henüz hayvan modellerinde ölçülebilir olabilir, bu motor ve bilişsel işlev ve duygusal davranış değişiklikleri mantıklı bir hayvan modellerinde beyin sarsıntısı değerlendirmek içi...

Sarsıntı da adlandırılan hafif travmatik beyin hasarı (HTBH), travmatik beyin hasarı (TBI) en sık görülen bir durumdur ve ABD&#39;de milyonlarca insanı etkilemektedir. Beyin sarsıntısı teşhis etmek zor olabilir ve sarsıntı için özel bir tedavisi yoktur. Büyüyen bir tanıma ve spor yaralanmaları, askeri mücadele ve diğer fiziksel ilgi çekici takipçiliği kaynaklanan hafif mekanik travma kümülatif ve kronik nörolojik sonuçları 1,2 olabileceği bazı kanıtlar vardır. Ancak, yine de sarsıntı ve onların etkilerine ilişkin bir bilgi eksikliği vardır. Sadece nörolojik değerlendirme ve görüntüleme değerlendirilmesi klinik tanı için kullanılabilir çünkü Güncel metodoloji insanlarda patoloji ve tedavi çalışmalarını kısıtlar. Hayvan modelleri, teşhis ve daha HTBH tedavisinde umut etkili, sıkı, ve kontrollü bir şekilde beyin sarsıntısı incelemek için bir araç sağlar. Çalışmalar geleneksel TBI adapte olmasıBöyle kontrollü kortikal etkisi (CCİ) olarak modeller, sıvı-perküsyon etkisi (FPI), ağırlık düşüşü yaralanma ve patlama hasarı HTBH gerçekleştirmek ve yaralanma parametreleri değiştirerek düşük yaralanma şiddet derecelerine uyarmak için. Bu modeller nedeniyle klinik durumuna morfolojik olarak benzer beyin travması çoğaltmak kabiliyetlerine için kullanmak yararlıdır; Ancak, aynı zamanda kendi sınırlamaları vardır. Bir ivme yaralanma (ağırlık damla) ile uyarılan yaralanma şiddeti genellikle oldukça değişkendir. Hafif CCI iki sonuçları - subaraknoid kanama ve fokal kontüzyon - tipik insan sarsıntı ile karşılaştırılabilir değildir. Blast yaralanma maruz 3-6 esnasında farklı pozlama pozisyon ve pik basınç ölçümleri açısından daha tartışmalı bir model yanı sıra değişken ikincil yaralanma ise CCİ ve FPI, klinik açıdan anlamlı olmayan bir kranyotomi gerektirir. Güncellenmiş sarsıcı hayvan modeli klinik Setti içine pre-klinik araştırma çevirebilirng araştırma gereklidir. Hafif TBI modelleme önemli bir konu en yakın bir klinik ortamda yaralanma çoğaltır deneysel yaralanma şiddetini, tanımlamaktır. Son zamanlarda, farklı araştırma grupları kapalı kafa travması veya Kafa travması (CHI) modeli 7-10 geliştirdi. CHI bir kraniotomi olmadan CCİ&#39;nin bir değişiklik, ama yine de bir kafa etkisini oluşturmak için geleneksel elektronik manyetik darbe sistemi kullanır. Bir CHI darbe parametrelerini ayarlayarak hafif ve orta şiddette değişen bir sarsıntı neden olabilir. bilinç (LOC) kaybı solunum hızı ya da solunum geçici fesih bir azalma tespit ederek bir darbeden sonra hemen görülebilir. LOC süresi yaralanmanın şiddetini belirlemek için kullanılır. Bu kağıt ayrıntılı adım-adım protokolü ve temsilcisi sonuçları ile birlikte farelerde tekrarlayan CHI (rCHI) modelin biraz geliştirilmiş ve güncelleştirilmiş bir sürümünü içerir. rCHI modeli araştırma stratejileri,sarsıntı kaynaklı patolojik değişikliklerin tümünü taklit edebilen hiçbir bireysel bir hayvan modeli var, özellikle de HTBH etkileri ve potansiyel tedaviler belirlenmesinde yararlı yeniden.

<table><tbody><tr><td>anesthesia machine</td><td>Eagle Eye Anesthesia, Inc</td><td>Model 150&amp;nbsp;</td><td>anesthesia</td></tr><tr><td>Electromagnetic Impactor</td><td>LeicaBiosystems</td><td>Impact One Stereotaxic Impactor</td><td>perform impaction</td></tr><tr><td>Digital Stereotaxic instrument</td><td>LeicaBiosystems</td><td>39462501</td><td>mount mouse and positioning tips</td></tr><tr><td>Sicilone rubber-coated metal tip</td><td>Precision Tool &amp;amp; Engineering, Gainesvill FL</td><td>custom-made</td><td>impact tip</td></tr><tr><td>Lithium Ion All-in-One Trimmer</td><td>WAHL Home Products</td><td>9854-600</td><td>shave mouse hair</td></tr><tr><td>paper clips</td><td>custom-made</td><td></td><td>probe tip</td></tr><tr><td>Cotton tipped applicators</td><td>MEDLINE</td><td>MDS202055</td><td>scrub head with saline</td></tr><tr><td>Tissue Tek O.C.T.</td><td>ASKURA FINETEK USA INC</td><td>4583</td><td>tissue embedding</td></tr><tr><td>anti-GFAP</td><td>Dako</td><td>CA93013</td><td>antibody for IHC</td></tr><tr><td>anti Ferritin</td><td>Sigma</td><td>F6136</td><td>antibody for IHC</td></tr><tr><td>VECTASTAIN Elite ABC&amp;nbsp; kit</td><td>Vector laboratories</td><td>PK-6100</td><td>IHC detection system</td></tr><tr><td>Permount Mounting Medium</td><td>Fisher Scientific</td><td>SP15-100</td><td></td></tr><tr><td>Aperio XT ScanScope scanner</td><td>Leica Microsystems Inc,</td><td></td><td>slides scanning</td></tr><tr><td>Leica AutoStainer XL</td><td>Leica the pathology Company</td><td>ST2010</td><td>H&amp;amp;E staining</td></tr><tr><td>DAB&amp;nbsp;</td><td>sigma</td><td>D3939</td><td>IHC detection system</td></tr></tbody></table>

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.

Bu modelde (Şekil 1 AC) ise, nefes nefese ve sığ respirations kısa dönemler vardı. (Bilinçsiz) bilinç kaybı solunum hızı veya normal solunumu devam etmeden önce nefes geçici fesih bir azalma olarak tanımlanır. Başın ortasına bir darbe kısa süreli bilinç kaybı nedeniyle (7.5 ± 4.7, ± 5.5 7.8, ± 8.8 10.2, ayrı ayrı etkisine 9.5 ± 8.0 sn, Şekil 1D). Fare beyinleri etkisi (Şekil 2A) bir sonucu olarak ortaya beli...

Watch this Scientific Journal Video about A Repetitive Concussive Head Injury Model in Mice at JoVE.com

A Repetitive Concussive Head Injury Model in Mice

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 ...

a-repetitive-concussive-head-injury-model-in-mice

Research

JoVE Journal

Medicine

11.8K Görüntüleme.  University of Florida. 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.

Video: A Repetitive Concussive Head Injury Model in Mice

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes 1,2. Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement 3,4. The resulting hematomas and lacerations cause a vascular response 3,5, and the morphological and functional damage of the white matter leads to diffuse axonal injury 6-8. Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure 9. Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals 10-12, which ultimately result in long-term neurological disabilities 13,14. Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair.
Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration 1. The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue 1,15. Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure 16,17. The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed skull 18. Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury 19. It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation 20.
We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP.

Lateral fluid percussion (LFP), an established model of traumatic brain injury in mice, is demonstrated. LFP fulfills three major criteria for animal models: validity, reliability and clinical relevance. The procedure, consisting of surgical craniotomy, fixation of hub followed by induction of injury, resulting in focal and diffuse injuries, is described.

Yanal Akışkan Perküsyon: Travmatik Beyin Hasarı Farelerde Modeli

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and ...

Nörobilim

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 ...

Tıp

A Novel and Translational Rat Model of Concussion Combining Force and Rotation with In Vivo Cerebral Microdialysis

Persistent cognitive and motor symptoms are known consequences of concussions/mild traumatic brain injury (mTBIs) that can be partly attributable to altered neurotransmission. Indeed, cerebral microdialysis studies in rodents have demonstrated an excessive extracellular glutamate release in the hippocampus within the first 10 min following trauma. Microdialysis offers the clear advantage of in vivo neurotransmitter continuous sampling while not having to sacrifice the animal. In addition to the aforementioned technique, a closed head injury model that exerts rapid acceleration and deceleration of the head and torso is needed, as such a factor is not available in many other animal models. The Wayne State weight-drop model mimics this essential component of human craniocerebral trauma, allowing the induction of an impact on the head of an unrestrained rodent with a falling weight. Our novel and translational rat model combines cerebral microdialysis with the Wayne State weight-drop model to study, in lightly anesthetized and unrestrained adult rats, the acute changes in extracellular neurotransmitter levels following concussion. In this protocol, the microdialysis probe was inserted inside the hippocampus as region of interest, and was left inserted in the brain at impact. There is a high density of terminals and receptors in the hippocampus, making it a relevant region to document altered neurotransmission following concussion. When applied to adult Sprague-Dawley rats, our combined model induced increases in hippocampal extracellular glutamate concentrations within the first 10 min, consistent with the previously reported post-concussion symptomology. This combined weight-drop model provides a reliable tool for researchers to study early therapeutic responses to concussions in addition to repetitive brain injury, since this protocol induces a closed-head mild trauma.

Neurotransmitter alteration is a mechanism of neural dysfunction that occurs after concussion and contributes to the sometimes-catastrophic long-term consequences. This rat model combines microdialysis, allowing in vivo neurotransmitter quantification, with a weight-drop technique exerting rapid acceleration and deceleration of the head and torso, an important factor of human craniocerebral trauma.

In vivo serebral mikrodiyaliz ile kuvvet ve rotasyonu birleştiren bir yeni ve translasyonel rat modeli

Persistent cognitive and motor symptoms are known consequences of concussions/mild traumatic brain injury (mTBIs) that can be partly attributable to ...

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 ...

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 ...

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 ...

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 ...

<meta charset="utf8"></head><body>ÇOCUK Modeli — Farelerde Çocuk Sarsıntısı ve Uzun Vadeli Sonuçların Özetlenmesi

A Pediatric Concussion Model in Mice: Closed Head Injury with Long-Term Disorders (CHILD)

Concussions and mild traumatic brain injuries (mTBI) during childhood represent a significant health endangerment, with many patients later in life exhibiting debilitating physiological, neurological, and psychosocial outcomes. The cellular and molecular pathophysiological mechanisms are relatively unknown, and this significant gap effectively precludes investigations into specific therapeutic strategies to mitigate chronic sequelae. No single animal concussion model recapitulates all the features reported in human subjects, and current models are designed to answer specific research questions. We set out to develop a juvenile concussion that recapitulates clinical early, and long-term symptomology encountered, termed Closed Head Injury with Long-term Disorder (CHILD). In this model, a concussive force via an electromagnetic impactor is delivered to the head of a lightly anesthetized unrestrained post-natal day 17 (P17) mouse, allowing free rotation of the head. Mice are placed on a tightly stretched tin foil across a stereotactic device, and the impactor is carefully aligned with the targeted cortical region. The electromagnetic impactor facilitates the selection of impact depth, dwell, and duration to determine injury severity. A strength of this model is that it allows head rotation, an important clinical feature. After impact, mice are immediately monitored for righting time and time to explore their environment, followed by their return to their dam. Increasing the severity of concussion results in intracranial bleeds in a subset of mice. Mice can be routinely monitored for behavior and neuroimaging over their lifespan, as desired. Various injury severities mimic the heterogeneous nature of juvenile concussions. The current standard CHILD model exhibits no skull fracture, no observable conventional neuroimaging change (similar to clinical), but leads to progressive and persistent neuronal death, altered diffusion MRI, modified neuronal activity and plasticity, increased gliosis, and progressive behavioral perturbations with age. In summary, this CHILD model mimics the early and long-term features observed in many clinical concussion patients.

<meta charset="utf8"></head><body>Farelerde Pediatrik Beyin Sarsıntısı Modeli: Uzun Süreli Bozukluklarla Kapalı Kafa Travması (ÇOCUK)

Pediatric concussions can result in long-term sequelae with physiological and psychological perturbations. This pediatric concussion mouse model results in long-term neuroinflammation, white matter alterations, and neuronal modifications with behavioral dysfunction. The model can be adapted to differential impact locations or repeated concussions to assess lifetime changes.

Farelerde Pediatrik Beyin Sarsıntısı Modeli: Uzun Süreli Bozukluklarla Kapalı Kafa Travması (ÇOCUK) 

Concussions and mild traumatic brain injuries (mTBI) during childhood represent a significant health endangerment, with many patients later in life ...

Farelerde Bir Tekrarlanan Concussive Kafa Travması Modeli

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Yanal Akışkan Perküsyon: Travmatik Beyin Hasarı Farelerde Modeli

Tek ve Tekrarlayan Hafif Travmatik Beyin Hasarı İçin Bir Fare Modeli

In vivo serebral mikrodiyaliz ile kuvvet ve rotasyonu birleştiren bir yeni ve translasyonel rat modeli

Travmatik Beyin Hasarı İndüksiyonu için Kontrollü Kortikal Etki Murine Modeli

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

Farelerde Hafif Travmatik Beyin Hasarının Elektromanyetik Kontrollü Kapalı Kafa Modeli

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

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

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

Farelerde Pediatrik Beyin Sarsıntısı Modeli: Uzun Süreli Bozukluklarla Kapalı Kafa Travması (ÇOCUK)