Bu çalışma, Ulusal Nörolojik Bozukluklar ve İnme Enstitüsü&#39;nden (MPB) R01 NS067417 tarafından desteklenmiştir.

Bu çalışmalar, Ulusal Sağlık Enstitüleri Laboratuar Hayvanlarının Bakımı ve Kullanımı Kılavuzu&#39;ndaki tavsiyelere tam uyacak şekilde yapılmıştır. Protokol, Georgetown Üniversitesi&#39;ndeki Kurumsal Hayvan Bakımı ve Kullanım Komitesi tarafından onaylandı. Fareler, sıcaklık kontrollü bir hayvan tesisinde barındırıldı ve 12 saat aydınlık / 12 saat karanlık döngüde tutuldu. Gıda ve su ad libitum mevcuttu. 1. mTBI Aparatının Hazırlanması NOT: mTBI cihazı, etki parametrelerini kontrol etmek için bir veri toplama (DAQ) kutusu, çarpma işlemini gerçekleştirmek için yüksek hızlı pnömatik darbe implantı ve çarpışmadan sonra kafayı yavaşlatmak için kalıplanmış bir jel doldurma tabanı içerir. <ol><li> Basınçlı havayı açın ve yüksek hızlı pnömatik çarpma tertibatını 861.85 kPa basınç ayarına getirin. </li><li> DAQ kontrol sistemini aşağıdaki parametrelere ayarlayın - piston hızı 2,35 m / s, yüzey durma zamanıE 31.5 ms. </li><li> Kalıplanmış jel dolgulu tabanı (sıkıştırılabilirlik 64 kPa / mm) orta çizginin çarpma uçlarının yörüngesine dik olacak şekilde yerleştirin. </li></ol> 2. mTBI Etkileşimi <ol><li> Kullanılacak olan tüm farelerin ağırlıklarını kaydedin. </li><li> Bir indüksiyon odasında 120 saniye boyunca oksijen içinde% 3 izofluran ile farelere anestezi uygulayın. </li><li> Fareleri mTBI aparatına aktarın, esnek, sabit olmayan burun konisi vasıtasıyla anestezi devam edin. </li><li> Burun konisinde iken fare kafasını jel yatağının üzerine yerleştirin, böylece kafatasının düz yüzeyi impaktorun ucuna dik olarak sunulur. </li><li> Yassı bir yüzey oluşturmak için kulaklıkları farenin üzerine yerleştirin ve kulakları etkilenen bölgeden uzak tutun. </li><li> Kafanın ortasındaki sagital orta hattına hizalamak için politetrafloroetilen çarpma ucunu indirin. Kullanılan çarpma ucu çapı 10 mm çapındadır ve gözlerin hemen arkasından kulak orta çizgisine kadar saç derisi alanını kaplar. Çarpıştırıcıyı ju ayarlayın.St fare kafasının yüzeyine dokunarak. </li><li> Darbe ucunu geri çekin ve gerekli sapma derinliğini (7.5 mm) manuel olarak çevirin. </li><li> DAQ kontrol sistemini çalıştırın ve fare kafasını etkilemek için tetikleyici düğmesine basın, tekil veya tekrarlayan etkiler. Tekrarlayan etkiler, her etki arasında gecikme olmaksızın arka arkaya teslim edilir. </li><li> Nihai etkinin hemen ardından fareyi anesteziden ve mTBI aparatından çıkarın ve yatay pozisyona getirin. </li><li> Bir kronometre kullanmak, sağır refleksin geri dönüş gecikmesini (sırtüstü eğilimli olarak) ölçerek, bilinç kaybının yanı sıra ambulasyon zamanı (engellenmeden yürüme) belirlemek için kullanılır. </li><li> Fare monitörünü ve normal duruma dönünce, eve dönün kafesine dönün. </li><li> Sham fareler aynı kullanım ve anestezi alır, ancak etki yaratmazlar. </li></ol>

<ol>
	<li>McMahon, P., 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=Symptomatology+and+functional+outcome+in+mild+traumatic+brain+injury:+results+from+the+prospective+TRACK-TBI+study.">Symptomatology and functional outcome in mild traumatic brain injury: results from the prospective TRACK-TBI study.</a> J Neurotrauma. 31 (1), 26-33 (2014).</li><li>Barkhoudarian, G., Hovda, D. A., Giza, C. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+molecular+pathophysiology+of+concussive+brain+injury.">The molecular pathophysiology of concussive brain injury.</a> Clin Sports Med. 30 (1), 33-48 (2011).</li><li>Blennow, K., Hardy, J., Zetterberg, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+neuropathology+and+neurobiology+of+traumatic+brain+injury.">The neuropathology and neurobiology of traumatic brain injury.</a> Neuron. 76 (5), 886-899 (2012).</li><li>Levin, H. S., Diaz-Arrastia, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosis,+prognosis,+and+clinical+management+of+mild+traumatic+brain+injury.">Diagnosis, prognosis, and clinical management of mild traumatic brain injury.</a> Lancet Neurol. 14 (5), 506-517 (2015).</li><li>McCrory, P., 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=Consensus+statement+on+concussion+in+sport:+the+4th+International+Conference+on+Concussion+in+Sport,+Zurich,+November+2012.">Consensus statement on concussion in sport: the 4th International Conference on Concussion in Sport, Zurich, November 2012.</a> J Athl Train. 48 (4), 554-575 (2012).</li><li>Talavage, T. 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=Functionally-detected+cognitive+impairment+in+high+school+football+players+without+clinically-diagnosed+concussion.">Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion.</a> J Neurotrauma. 31 (4), 327-338 (2014).</li><li>Angoa-Perez, 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=Animal+models+of+sports-related+head+injury:+bridging+the+gap+between+pre-clinical+research+and+clinical+reality.">Animal models of sports-related head injury: bridging the gap between pre-clinical research and clinical reality.</a> J Neurochem. 129 (6), 916-931 (2014).</li><li>Creed, J. 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=Concussive+brain+trauma+in+the+mouse+results+in+acute+cognitive+deficits+and+sustained+impairment+of+axonal+function.">Concussive brain trauma in the mouse results in acute cognitive deficits and sustained impairment of axonal function.</a> J Neurotrauma. 28 (4), 547-563 (2011).</li><li>Hamberger, 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=Concussion+in+professional+football:+morphology+of+brain+injuries+in+the+NFL+concussion+model--part+16.">Concussion in professional football: morphology of brain injuries in the NFL concussion model--part 16.</a> Neurosurgery. 64 (6), 1174-1182 (2009).</li><li>Kane, M. J., 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> J Neurosci Methods. 203 (1), 41-49 (2012).</li><li>Prins, M. L., 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=Repeat+traumatic+brain+injury+in+the+juvenile+rat+is+associated+with+increased+axonal+injury+and+cognitive+impairments.">Repeat traumatic brain injury in the juvenile rat is associated with increased axonal injury and cognitive impairments.</a> Dev Neurosci. 32 (5-6), 510-518 (2010).</li><li>Tang, Y. P., 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+concussive-like+brain+injury+model+in+mice+(II):+selective+neuronal+loss+in+the+cortex+and+hippocampus.">A concussive-like brain injury model in mice (II): selective neuronal loss in the cortex and hippocampus.</a> J Neurotrauma. 14 (11), 863-873 (1997).</li><li>Winston, C. N., 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=Dendritic+Spine+Loss+and+Chronic+White+Matter+Inflammation+in+a+Mouse+Model+of+Highly+Repetitive+Head+Trauma.">Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma.</a> Am J Pathol. 186 (3), 552-567 (2016).</li><li>Johnson, V. E., 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=Inflammation+and+white+matter+degeneration+persist+for+years+after+a+single+traumatic+brain+injury.">Inflammation and white matter degeneration persist for years after a single traumatic brain injury.</a> Brain. 136, 28-42 (2013).</li><li>Barrio, J. R., 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=In+vivo+characterization+of+chronic+traumatic+encephalopathy+using+[F-18]FDDNP+PET+brain+imaging.">In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.</a> Proc Natl Acad Sci U S A. 112 (16), 2039-2047 (2015).</li></ol>

Yazarların açıklayacak bir şeyi yok.

İnsanlarda, mTBI, yapısal yaralanmanın olmadığı bir işlevsel bozukluk ile karakterizedir. Bu, bilinç kaybıyla ya da ortaya çıkmadan ortaya çıkabilir 1 . Sarsıntıları tekrarlamak için maruz kalınmanın şu anda CTE 4 gibi nörodejeneratif hastalıkların gelişimi ve / veya ilerlemesinin altında yattığı düşünülmektedir. CTE&#39;nin boksörler ve futbolcuların yaygın bir şekilde bulunduğu belirtilmektedir ve tekrarlanan sarsıntılara maruz kalm...

Travmatik Beyin Yaralanması (TBI), normal bir beyin işlevinin bozulmasına neden olan, dış bir fiziksel kuvvetten gelen bir kafa yaralanması olarak tanımlanır. Hastalık Kontrol ve Önleme Merkezi 2015 Kongre Raporu ile 2.5 milyon Amerikalı&#39;nın her yıl bir TBH&#39;yi sürdürdüğünü tahmin ederek önemli bir sosyo-ekonomik ve halk sağlığı yükü oluşturuyor. Bu sadece hastanın yaşam kalitesini etkilemekle kalmaz aynı zamanda yıllık olarak 76.5 milyar dolar olarak tahmin edilen topluluğa son derece yüksek bir ekonomik maliyet getirir. Gerçek beyin hasarının miktarı ve akut faz semptomları, hafif, orta ve şiddetli TBI&#39;yi tanımlayan şeydir. Hafif travmatik Beyin Hasarı (mTBI), ayrıca sarsıntı olarak da bilinir, her yıl bildirilen TBİ&#39;lerin% 70&#39;inden fazlasını oluşturur 1 . Boks ve futbol gibi yüksek riskli temas sporlarına katılan sporcular arasında en yaygın olanıdır 2 . Ilımlıdan farklı olarakVeya şiddetli TBI formlarında, mTBI ile ilişkili derhal hasar ve semptomlar bazen belirgin değildir 3 . Buna karşılık, mTBI&#39;nin uzun vadeli etkileri, ılımlı ve şiddetli formlarda görülen kadar zayıflatıcı olabilir. Tekrarlayan mTBI muzdarip kişilerin kronik travmatik ensefalopati (CTE) yanı sıra diğer kognitif ve dejeneratif hastalıklar geliştiği gösterilmiştir 4 . Bu nedenle, kısa vadeli semptomlara ve mTBI sonrasında ortaya çıkan uzun vadeli hasarlara katkıda bulunan mekanizmalar hakkında daha fazla bilgi edinmek önemlidir. İnsanlarda, Dördüncü Sporda Sarsılma Konferansı (Zurich 2012) 5 tarafından tanımlanan sarsıntı tanımında, spor sarsıntısı yaralanma seviyesinin hafif, patolojik değişikliklere neden olmadığı, ancak kısa süreli nörolojik defisitlere neden olduğu belirtilmektedir Bu kendiliğinden çözülmüştür. Gerçekten de, bir alNt çalışması, mTBI&#39;nin kafa etki telemetri sistemlerini kullanan lise futbolcularındaki kognitif bozukluk üzerindeki etkisini araştırmıştır. Bu çalışma, oyuncuların tek seferde 226&#39;dan düşük (ortalama 4.7 / dönem) ila 1855 (ortalama 38.6 / dönem) arasında kask etkisi&gt; 20 g sürdürdüklerini gösterdi. Bu etkilerin çoğu klinik olarak sarsıntı teşhisi ile sonuçlanmadı; FMRI 6 kullanılarak beyin fonksiyonlarındaki fonksiyonel değişikliklerin kanıtı gözlemlenebilir. Bu işlevsel değişikliklerin sebep olduğu beyin değişiklikleri bilinmiyor ve dolayısıyla konkasif ve altta yatan mTBI&#39;nın etkilerini araştırmak için güvenilir ve tekrarlanabilir bir modele ihtiyaç duyulmaktadır. Fareler ve sıçanlarda mTBI&#39;nin modellenmesine yönelik daha önceki girişimlere rağmen, birçok rapor advers etkiler. Özellikle, çoğu kemirgen modelin tekrar eden doğası daha sınırlıdır.Beş mTBI, intraserebral kanama, kafatası kırıkları, ciddi aksonal yaralanma, nöronal hücre ölümü ve artan mortalite gibi olumsuz patolojik olayların yanı sıra etkiler 8 , 9 , 10 , 11 , 12 . Burada insanlardaki sarsıntıların gerçek tanımına daha yakın bir mTBI fare modelini açıklıyoruz. Bu model insan mTBI&#39;sında gözlemlenen semptomların birçoğunu tekrarlar; örneğin açık beyin patolojisi olmayan bilinç kaybı ile sonuçlanan mekanik kuvvet gibi. Ayrıca, daha önce bildirildiği gibi, tek etkili ve tekrarlayıcı etki paradigmaları için uzun zaman periyotları için kullanılabileceği için avantajlıdır 13 .

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a mouse model of single and repetitive mild traumatic brain injury

Hafif Travmatik Beyin Hasarı (mTBI), bir karışıklık dönemi, bilinç kaybı (LOC), fokal nörolojik defisitler ve hatta amnezi gibi akut beyin fonksiyon kaybına neden olabilir. Temas sporlarına katılan sporcular, çok sayıda mTB&#39;ye maruz kalma riski yüksektir. Sporcu bir sporcudaki yaralanma seviyesi açısından mTBI, hafif patolojik değişikliklere neden olmayan hafif bir yaralanma olarak tanımlanır, ancak kendiliğinden çözülen kısa süreli nörolojik defisitlere neden olur. Fareler ve sıçanlarda mTBI&#39;yi modellemek için önceki girişimlere rağmen, birçok kişi kafatası kırıkları, intraserebral kanama, aksonal yaralanma ve nöronal hücre ölümü gibi ciddi yan etkileri bildirmiştir. Burada, klinik olarak ilgili semptomları çoğaltan mTBI&#39;nin tekrar üretilebilir hayvan modelini tanımlıyoruz. Bu model, kapalı kafa travması vermek için özel yapım pnömatik darbe cihazı kullanır. Bu etki, hassas hız ve deformasyon parametreleri altında yapılır,Tek veya tekrarlayan konussif mTBI&#39;nin etkilerine katkıda bulunan mekanizmaları incelemek için güvenilir ve tekrarlanabilir bir model oluşturur.

Bu yeni mTBI cihazının kullanımı kafatası kırığı veya yapısal beyin hasarı riski olmaksızın tekli ve tekrarlayan hafif kafa travmalarına izin verir. Model, kapalı kafalı mekanik enerji etkisi sağlamak için özel pnömatik bir Teflon çarpma aygıtı kullanıyor. Darbe, hassas hız ve deformasyon parametreleri altında yapılır ve tek veya tekrarlayan konussif mTBI etkilerine katkıda bulunan mekanizmaları incelemek için güvenilir ve tekrarlanabilir bir model oluştu...

Watch this Scientific Journal Video about A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury at JoVE.com

A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

Sporcular, her yıl birkaç yüz hafif travmatik beyin yaralanması (mTBI) / sarsıntıyı emerler; Bununla birlikte, bunların beynin üzerindeki sonuçları tam olarak anlaşılamamıştır. Bu nedenle, klinik olarak ilgili semptomları sürekli olarak çoğaltan tek ve tekrarlayan bir mTBI&#39;nin bir hayvan modeli mTBI ve sarsıntı çalışmalarını ilerletmenin yollarını sağlar.

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 ...

a-mouse-model-of-single-and-repetitive-mild-traumatic-brain-injury

Research

JoVE Journal

Medicine

11.0K Görüntüleme.  Georgetown University Medical Center.  Sporcular, her yıl birkaç yüz hafif travmatik beyin yaralanması (mTBI) / sarsıntıyı emerler; Bununla birlikte, bunların beynin üzerindeki sonuçları tam olarak anlaşılamamıştır. Bu nedenle, klinik olarak ilgili semptomları sürekli olarak çoğaltan tek ve tekrarlayan bir mTBI'nin bir hayvan modeli mTBI ve sarsıntı çalışmalarını ilerletmenin yollarını sağlar. 

Video: A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

Normothermic Cardiac Arrest and Cardiopulmonary Resuscitation: A Mouse Model of Ischemia-Reperfusion Injury

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused by whole-body hypoperfusion.5,6 Successful reproduction of whole-body hypoperfusion in rodent models has been fraught with 
difficulty.7-9,9,10 Models which employ focal ischemia have repeatedly demonstrated results which do not translate to the clinical setting, and larger 
animal models which allow for whole body hypoperfusion lack access to the full toolset of genetic manipulation possible in the mouse.11,12 However, in recent 
years a mouse model of cardiac arrest and cardiopulmonary resuscitation has emerged which can be adapted to model AKI.13 This model reliably reproduces 
physiologic, functional, anatomic, and histologic outcomes seen in clinical AKI, is rapidly repeatable, and offers all of the significant advantages of a murine surgical 
model, including access to genetic manipulative techniques, low cost relative to large animals, and ease of use. Our group has developed extensive experience 
with use of this model to assess a number of organ-specific outcomes in AKI.14,15

A powerful model for perioperative and critical care related acute kidney injury is presented. Using whole body hypoperfusion induced by cardiac arrest it is possible to nearly replicate the histologic and functional changes of clinical AKI.

Normotermik Kardiyak Arrest ve Kardiyopulmoner Resusitasyon: İskemi-Reperfüzyon Hasarı Fare Modeli

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused ...

Tıp

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for objective diagnosis but also for the evaluation of therapeutic efficacy and resilience to trauma. Ongoing research is directed at identifying molecular biomarkers for PTSD, including traumatic stress induced proteins, transcriptomes, genomic variances and genetic modulators, using biologic samples from subjects' blood, saliva, urine, and postmortem brain tissues. However, the correlation of these biomarker molecules in peripheral or postmortem samples to altered brain functions associated with psychiatric symptoms in PTSD remains unresolved. Here, we present an animal model of PTSD in which both peripheral blood and central brain biomarkers, as well as behavioral phenotype, can be collected and measured, thus providing the needed correlation of the central biomarkers of PTSD, which are mechanistic and pathognomonic but cannot be collected from people, with the peripheral biomarkers and behavioral phenotypes, which can.
Our animal model of PTSD employs restraint and tail shocks repeated for three continuous days - the inescapable tail-shock model (ITS) in rats. This ITS model mimics the pathophysiology of PTSD 17, 7, 4, 10. We and others have verified that the ITS model induces behavioral and neurobiological alterations similar to those found in PTSD subjects 17, 7, 10, 9. Specifically, these stressed rats exhibit (1) a delayed and exaggerated startle response appearing several days after stressor cessation, which given the compressed time scale of the rat's life compared to a humans, corresponds to the one to three months delay of symptoms in PTSD patients (DSM-IV-TR PTSD Criterian D/E 13), (2) enhanced plasma corticosterone (CORT) for several days, indicating compromise of the hypothalamopituitary axis (HPA), and (3) retarded body weight gain after stressor cessation, indicating dysfunction of metabolic regulation.
The experimental paradigms employed for this model are: (1) a learned helplessness paradigm in the rat assayed by measurement of acoustic startle response (ASR) and a charting of body mass; (2) microdissection of the rat brain into regions and nuclei; (3) enzyme-linked immunosorbent assay (ELISA) for blood levels of CORT; (4) a gene expression microarray plus related bioinformatics tools 18. This microarray, dubbed rMNChip, focuses on mitochondrial and mitochondria-related nuclear genes in the rat so as to specifically address the neuronal bioenergetics hypothesized to be involved in PTSD.

We describe a rat model of post traumatic stress disorder (PTSD) that reveals the persistent alterations in neuroendocrine function and the delayed long-term, exaggerated fear response, characteristic of PTSD patients. The animal model and methods described here are useful for correlating biomarkers in brain nuclei, which are mechanistic but cannot be measured in patients, with biomarkers in peripheral white blood cells, which can.

TSSB, Nöral Hematolojik ve Davranış Bağlantılı Revealing için Hayvan Modelinde Biyobelirteçler

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for ...

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 ...

An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse

Under normal conditions, the cornea is avascular, and this transparency is essential for maintaining good visual acuity. Neovascularization (NV) of the cornea, which can be caused by trauma, keratoplasty or infectious disease, breaks down the so called &lsquo;angiogenic privilege' of the cornea and forms the basis of multiple visual pathologies that may even lead to blindness. Although there are several treatment options available, the fundamental medical need presented by corneal neovascular pathologies remains unmet. In order to develop safe, effective, and targeted therapies, a reliable model of corneal NV and pharmacological intervention is required. Here, we describe an alkali-burn injury corneal neovascularization model in the mouse. This protocol provides a method for the application of a controlled alkali-burn injury to the cornea, administration of a pharmacological compound of interest, and visualization of the result. This method could prove instrumental for studying the mechanisms and opportunities for intervention in corneal NV and other neovascular disorders.

Neovascularization (NV) of the cornea can complicate multiple visual pathologies. Utilizing a controlled, alkali-burn injury model, a quantifiable level of corneal NV can be produced for mechanistic study of corneal NV and evaluation of potential therapies for neovascular disorders.

Fare Kornea Neovaskülarizasyonunun bir Alkali-yanık Yaralanma Modeli

Under normal conditions, the cornea is avascular, and this transparency is essential for maintaining good visual acuity. Neovascularization (NV) of the ...

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 Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls, a reliable animal model of mTBI had previously not been developed for this important aspect of development. The modified weight-drop technique employs a glancing impact to the head of a freely moving rodent transmitting acceleration, deceleration, and rotational forces upon the brain. When applied to juvenile rats, this modified weight-drop technique induced clinically relevant behavioural outcomes that were representative of post-concussion symptomology. The technique is a rapidly applied procedure with an extremely low mortality rate, rendering it ideal for high-throughput studies of therapeutics. In addition, because the procedure involves a mild injury to a closed head, it can easily be used for studies of repetitive brain injury. Owing to the simplistic nature of this technique, and the clinically relevant biomechanics of the injury pathophysiology, the modified weight-drop technique provides researchers with a reliable model of mTBI that can be used in a wide variety of behavioural, molecular, and genetic studies.

The modified weight-drop technique is an easy, cost-effective procedure used for the induction of mild traumatic brain injury in juvenile rats. This novel technique produces clinically relevant symptomology that will advance the study of mild traumatic brain injury (mTBI) and concussion.

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 ...

A Neonatal Mouse Spinal Cord Compression Injury Model

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life1, this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques1. Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections1.

This article describes a method for generating a reproducible spinal cord compression injury (SCI) in the neonatal mouse. The model provides an advantageous platform for studying mechanisms of adaptive plasticity that underlie spontaneous functional recovery.

Bir Yenidoğan Fare Omurilik Sıkıştırma Yaralanması Modeli

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal ...

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 ...

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 ...