LT Üniversitesi Tıp Göttingen Forschungsförderungsprogramm gelen hibe desteği almıştır. PL ve MB Beyin (CMPB), Göttingen Moleküler Fizyoloji için DFG Araştırma Merkezi tarafından desteklendi. Yazarlar, ses ve video düzenleme ile yardım videografisi ve Birgit Liebau yardım için Dr Lars Tatenhorst teşekkür ederim.

Hayvanlar Jackson Laboratory (# 002.726) 1 den satın alınmıştır. Onlar klinik attı ve motor fonksiyon (rotarod testi) ve kas gücü (tel deneyi asılı) bir teste tabi tutulmaktadır. Tüm bu testleri ve hayvanların daha sonra öldürülmesi omurilik hazırlamak amacıyla hayvan deneyleri bir şekilde yürütülmesi için Yerel yönergelere çok yakın uygun olarak yapılmıştır. 1. Klinik Puan Apart vücut ağırlığı fareler için değerlendirme aşağıdaki 4 nokta skorlama sistemi 2 ile motor defisit belirtileri açısından incelenir: 4 puan: Normal (motor disfonksiyon bulgusu) 3 puan: kuyruk tarafından askıya zaman arka bacak titreme belirgindir 2 puan: yürüyüş anormallikleri mevcut 1 puan: en az bir arka bacak sürükleyerek 0 puan: simetrikfelç, kendisinin sağ yeteneksizliği ve maksimum vücut ağırlığının% 20 kaybı, bu durumda, hayvanlarda hemen ötenazi ve deney sona erdirilir 2. Motor Fonksiyon Testleri ve Kas Gücü Tel Hanging Bu test, kas gücü 3, 4 değerlendirmek için kullanılmıştır. Tüm hayvanlar en az bir veya iki gün rotarod testinden sonra bu testi yapın. Her fare 0.8 cm aralıklarla özel yapılmış tel kapak yerleştirilir ve dikkatli tepetaklak olur, bir saman üstünde 60 cm alt kaplı. En az 180 s art arda üç kez eğitim aldıktan sonra düşmeye gecikme ölçülür. Her fare, 180 s maksimum ve en uzun süre kaydedilir için ters kapak üzerinde tutmak için üç deneme verilir. Rotarod Testi 3, 4 öğrenme ölçmek için kullanılmıştır. İyi bir performans sensorimotor koordinasyonu yüksek derecede gerektirir. Makine test hayvan için Distraktif uyaranlara önlemek için sakin ve rahatsız edici olmayan bir ortamda yer almalıdır. Bu beş fareler için bir bilgisayar kontrollü motorlu dönen milli ve beş şerit oluşur. Farelerin Falls altındaki bir plastik levha üzerine basınç ile otomatik olarak tespit edilir. 15 rpm bir hayvan dönen çubuk kalabilecekleri süreyi sabit bir hızda en az 180 s art arda üç kez eğitim ölçülür sonra. Her hayvan düşüyor kaydedilir olmadan üç denemeler ve uzun gecikme uğrar. Motor koordinasyonu açısından önemli farklılıklar çoğunluğu bu süre içinde tespit edilir, çünkü 180 s zaman kesme süresi olarak seçilmiştir. 3. Omurilik Hazırlık <ol class="lalpha"><li> Hayvanlar Yerel yönergelere uygun olarak CO 2 insuflasyon tarafından öldürüldü ve hemen% 4 paraformaldehit çözümü takip PBS çözeltisi ile transkardiyal perfüze edilir. </li><li> Kurban fare spinal kord hazırlamak için, bir farenin arka tarafı açığa çıkarmak için hayvanın bir işlem tablosu üzerine yerleştirilir ve dört ayaklarının tarafında sabitlenir. </li><li> % 70 etanol çözeltisi ile kısa bir yıkama diseksiyon sitesi temizler ve saç kat düzleştirir. </li><li> Sonra cildin orta hat keskin bir bisturi ile insize edilir. Cilt her iki taraf için gerilir kesme kolaylaştırmak için. Bacak kasları hazırlanacak olursa, onların deri de insize lazım. </li><li> Cilt insizyonu tamamlandıktan sonra, vücudun alttaki fasyaya maruz cımbız ile kenara çekilir. </li><li> Boyun ve ense ligament kas ca kaldırılması gerekir ve vardırrefully hazırlanır. Derin ve lezyon omuriliğe kesilirken dikkat edin. Omuz kaslarının daha iyi omurga ortaya koymak için çıkarılabilir. </li><li> Sonra paravertebral kas tamamını omurga kaldırılır. </li><li> Omurga çok laminektomileri yapılması gerekir açmak üzere. Bir atlanto oksipital eklem yerinde üst kranial kısmından başlamalıdır. </li><li> Bu üst iki ekstremite fiksasyon kaldırmak ve ilk vertebra laminektomi gerçekleştirmek için daha iyi yapabilmek için boyun yayılmacılık en kolay yoldur. Bunlar maruz servikal spinal kord dokunmadan çekti edilir. </li><li> Daha çok omurun açılı ilk makasla her iki tarafında vertebra kemerler transecting ve sonra dorsal işlemleri üzerinde çekme ile kaldırılır. Vertebra Kalan yan kısımlarında omurilik sonra tümüyle kaldırılmasını kolaylaştırmak için çıkarılmalıdır. </li><li> Lomber spina bir anatomik dönüm noktasıl kordonu da spinal kord mevcuttur kabarma olup. </li><li> Tüm omurilik laminektomi bitirdikten sonra, aynı zamanda tüm ventral kökleri transeksiyonu ve menenjlerin duramater gelen spinal kord serbest olduğundan emin olun. </li><li> Daha sonra servikal spinal kord kranialine kesilmiş ve omurilik kaldırmak başlatın. </li><li> Son olarak omuriliğe de tamamen serbest olması distal kauda-equina kesilir. </li><li> Sonuçta, omurilik gecede postfixating çözüm (örneğin% 4 paraformaldehit) yerleştirilir ve daha fazla işlenebilir. Biz genellikle immünohistolojik analiz hazırlamak için omurilik cryosection. </li></ol> 4. Temsilcisi Sonuçlar Omurilik hazırlama tekniği bu video makalenin odak temsil eder. Daha sonra doku kesit ve sonuçta spina ile immünohistolojik analizi için gerekli bir ön koşuldurl kablosu bölümler. Bir sonuç bir örnek olarak, bir wild tip bir fare lumbar spinal kord (wt) ön boynuzu bölge ve bir SOD G93A transgen (Tg) ve bir ayırma işlemlerine tabi tutmak immunohistokimyasal fare gösterilmiştir. Motor nöronlar, bir primer, anti-ChAT antikor ve bir ikincil Cy3 antikoru ile sonradan flüoresan etiketleme ile tespit edilebilir. Buna ek olarak, DAPI (4,6-diamidino-2-fenilindol) ile bir karşı-Nükleer leke (Şekil 1) yapılmıştır. <img src="/files/ftp_upload/3936/3936fig1.jpg" alt="Şekil 1" /> Şekil 1. Anti-ChAT antikor (kırmızı) ve wild tip (ağırlık), fare lomber spinal kord ön boynuz (solda) ve bir DAPI (mavi) ile hücresel çekirdekleri karşı leke ile motonöronlar ve İmmuno görselleştirmek Floresan fotomikrografı Bir SOD G93A transgenik (tg) (sağda) 130 gün yaşındayken fare. Ölçek çubuğu: 40 mikron. Ve immünohistokimyasal analiziSOD G93A farelerin bu makalenin ana kapsamında değildir bu transgenik fareler karakterize edildiği orijinal yayın ve diğer referans 1, 5, 6 yönelik tedavi yaklaşımları incelemek daha yeni olanlarla danışın. Tedavi edici etkileri açıkça tanımlanmış immünohistolojik düzeyde ayırt edilir ise kantitatif değerlendirme algoritmaları stereolojik bir yazılım (örneğin 7) tarafından desteklenen uygulanan edilmelidir.

<ol>
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L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuromuscular+disease+models+and+analysis.">Neuromuscular disease models and analysis.</a> Methods Mol. Biol. 602, 347-393 (2010).</li><li>Hayworth, C. R., Gonzalez-Lima, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pre-symptomatic+detection+of+chronic+motor+deficits+and+genotype+prediction+in+congenic+B6.SOD1(G93A)+ALS+mouse+model.">Pre-symptomatic detection of chronic motor deficits and genotype prediction in congenic B6.SOD1(G93A) ALS mouse model.</a> Neuroscience. 164 (3), 975-985 (2009).</li><li>Ludolph, A. 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Çıkar çatışması ilan etti.

SOD1 (G93A) genetik fare modelinde insan Amyotrofik lateral skleroz 8 karşılaştırılabilir ilerleyici motor nöron kaybı, hastalığın klinik seyrini incelemek için değerli bir hayvan modelidir. Farklı tedavi paradigmalarının çeşitli bu modelin içinde değerlendirilerek daha sonra insan klinik çalışmalarda 8-10 test için bir temel temsil edilmiştir. Bu farelerde deneysel bir tedavi çalışmasında önemli farklılıklar tespit edebilmek için, en az 24 çöp eşleştirilmiş cin...

<table border="1"><tbody><tr><td></td><td> Üretici </td><td> Sipariş Bilgileri </td></tr><tr><td> Davranışsal test </td><td></td><td></td></tr><tr><td> Fareler için Rota-Rod </td><td> Ugo Basile, Comerio, İtalya </td><td> # 47600 </td></tr><tr><td> Tel cihazı Hanging </td><td> Ismarlama </td><td></td></tr><tr><td colspan="3"></td></tr><tr><td> Omurilik Hazırlık </td><td></td><td></td></tr><tr><td> Ameliyat Masası Çalışma lambası Koruyucu eldivenler </td><td></td><td></td></tr><tr><td> Tarafına açılı &quot;Iris&quot; Makas, </td><td> Güzel Bilim Araçlar, Heidelberg, Almanya </td><td> 14063-09 </td></tr><tr><td> Cohan-Vannas Bahar Makas, düz </td><td> Güzel Bilim Araçlar, Heidelberg, Almanya </td><td> 15000-10 </td&gt; </tr><tr><td> Mikro forseps </td><td> Hammacher, Solingen, Almanya </td><td> HWC 111-10 </td></tr><tr><td> Neşter &quot;präzisa plus&quot; </td><td> Dahlhausen, Köln, Almanya </td><td> 11.000.00.510, ŞEKİL 10 </td></tr></tbody></table>

clinical testing and spinal cord removal in a mouse model for amyotrophic lateral sclerosis (als)

Amyotrofik lateral skleroz (ALS) motonöronlar ilerleyici dejenerasyon ile sonuçlanan ölümcül bir nörodejeneratif hastalıktır. Başlangıçlı Tepe sporadik hastalık ve ailesel hastalık için 50 yıl 60 yıl civarındadır. Ilerici seyri nedeniyle, hastaların% 50 semptom başlangıcından itibaren 30 ay içinde ölür. Bu hastalığın tedavisi için yeni bir seçenek değerlendirmek üzere, ALS genetik fare modelleri gibi SOD1 (G93A) mutasyonu olarak SOD geni insan ailevi mutasyonlar, esas oluşturulan edilmiştir. Modelinde değerlendirilmesi gerekir en önemli husus, genel sağkalım, klinik seyir ve motor fonksiyon vardır. Burada, klinik değerlendirme göstermek, iki davranışsal motor testleri ile iletim göstermek ve tüm parametreler için kantitatif skorlama sistemleri sağlamaktadır. ALS fare modelinin kapsamlı bir analizi genellikle spinal kord bir immunohistokimyasal inceleme gerektirdiğinden, biz bunu uygulayarak ayrıntılı olarak hazırlanması göstermekrsal laminektomi yöntemi. Örnek histolojik bulgular gösterilmiştir. ALS fare modeli üzerinde çalışmalar tasvir muayene yöntemlerinin kapsamlı bir uygulama araştırmacının güvenilir sonra insan klinik araştırmalar için bir temel sağlayabilir gelecekteki tedavi seçenekleri test sağlayacaktır.

Watch this Scientific Journal Video about Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis ALS at JoVE.com

Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis ALS

Amiyotrofik lateral skleroz (ALS) için bir fare modelinde klinik ve davranışsal incelenmiştir. Beraberindeki immünohistolojik analizi için bir önkoşul olarak omurilik hazırlanmasında detaylı bir şekilde anlatılır.

Amyotrofik Lateral Skleroz için Fare Modeli (ALS) Klinik Test ve Omurilik Kaldırma

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in progressive degeneration of motoneurons. Peak of onset is around 60 ...

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Research

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Medicine

Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis (ALS)

28.0K Görüntüleme.  University Medicine Göttingen. Amiyotrofik lateral skleroz (ALS) için bir fare modelinde klinik ve davranışsal incelenmiştir. Beraberindeki immünohistolojik analizi için bir önkoşul olarak omurilik hazırlanmasında detaylı bir şekilde anlatılır.

Video: Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis ALS

A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis (ALS)

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression across speech subsystems, and for addressing the critical need for sensitive outcome measures for ongoing experimental treatment trials. To address this need, we are obtaining longitudinal profiles of bulbar impairment in 100 individuals based on a comprehensive instrumentation-based assessment that yield objective measures. Using instrumental approaches to quantify speech-related behaviors is very important in a field that has primarily relied on subjective, auditory-perceptual forms of speech assessment1. Our assessment protocol measures performance across all of the speech subsystems, which include respiratory, phonatory (laryngeal), resonatory (velopharyngeal), and articulatory. The articulatory subsystem is divided into the facial components (jaw and lip), and the tongue. Prior research has suggested that each speech subsystem responds differently to neurological diseases such as ALS. The current protocol is designed to test the performance of each speech subsystem as independently from other subsystems as possible. The speech subsystems are evaluated in the context of more global changes to speech performance. These speech system level variables include speaking rate and intelligibility of speech.
The protocol requires specialized instrumentation, and commercial and custom software. The respiratory, phonatory, and resonatory subsystems are evaluated using pressure-flow (aerodynamic) and acoustic methods. The articulatory subsystem is assessed using 3D motion tracking techniques. The objective measures that are used to quantify bulbar impairment have been well established in the speech literature and show sensitivity to changes in bulbar function with disease progression. The result of the assessment is a comprehensive, across-subsystem performance profile for each participant. The profile, when compared to the same measures obtained from healthy controls, is used for diagnostic purposes. Currently, we are testing the sensitivity and specificity of these measures for diagnosis of ALS and for predicting the rate of disease progression. In the long term, the more refined endophenotype of bulbar ALS derived from this work is expected to strengthen future efforts to identify the genetic loci of ALS and improve diagnostic and treatment specificity of the disease as a whole. The objective assessment that is demonstrated in this video may be used to assess a broad range of speech motor impairments, including those related to stroke, traumatic brain injury, multiple sclerosis, and Parkinson disease.

A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis ALS

Objective assessments of the physiological mechanisms that support speech are needed to monitor disease onset and progression in persons with ALS and to quantify treatment effects in clinical trials. In this video, we present a comprehensive, instrumentation-based protocol for quantifying speech motor performance in clinical populations.

Amyotrophic Lateral Sclerosis bulber Disfonksiyon Kapsamlı Değerlendirmesi (ALS) için Protokol

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression ...

Tıp

Intraspinal Cell Transplantation for Targeting Cervical Ventral Horn in Amyotrophic Lateral Sclerosis and Traumatic Spinal Cord Injury

Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) cases 1 and is the ultimate cause of death in patients with the motor neuron disorder, amyotrophic laterals sclerosis (ALS) 2.
ALS is a devastating neurological disorder that is characterized by relatively rapid degeneration of upper and lower motor neurons. Patients ultimately succumb to the disease on average 2-5 years following diagnosis because of respiratory paralysis due to loss of phrenic motor neuron innnervation of the diaphragm 3. The vast majority of cases are sporadic, while 10% are of the familial form. Approximately twenty percent of familial cases are linked to various point mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene on chromosome 21 4. Transgenic mice 4,5 and rats 6 carrying mutant human SOD1 genes (G93A, G37R, G86R, G85R) have been generated, and, despite the existence of other animal models of motor neuron loss, are currently the most highly used models of the disease.
Spinal cord injury (SCI) is a heterogeneous set of conditions resulting from physical trauma to the spinal cord, with functional outcome varying according to the type, location and severity of the injury 7. Nevertheless, approximately half of human SCI cases affect cervical regions, resulting in debilitating respiratory dysfunction due to phrenic motor neuron loss and injury to descending bulbospinal respiratory axons 1. A number of animal models of SCI have been developed, with the most commonly used and clinically-relevant being the contusion 8.
Transplantation of various classes of neural precursor cells (NPCs) is a promising therapeutic strategy for treatment of traumatic CNS injuries and neurodegeneration, including ALS and SCI, because of the ability to replace lost or dysfunctional CNS cell types, provide neuroprotection, and deliver gene factors of interest 9.
Animal models of both ALS and SCI can model many clinically-relevant aspects of these diseases, including phrenic motor neuron loss and consequent respiratory compromise 10,11. In order to evaluate the efficacy of NPC-based strategies on respiratory function in these animal models of ALS and SCI, cellular interventions must be specifically directed to regions containing therapeutically relevant targets such as phrenic motor neurons. We provide a detailed protocol for multi-segmental, intraspinal transplantation of NPCs into the cervical spinal cord ventral gray matter of neurodegenerative models such as SOD1G93A mice and rats, as well as spinal cord injured rats and mice 11.

Neural precursor transplantation is a promising strategy for protecting and/or replacing lost/dysfunctional cervical phrenic motor neurons in spinal cord injury (SCI) and the motor neuron disorder, amyotrophic laterals sclerosis (ALS). We provide a protocol for cell delivery to cervical spinal cord ventral horn in rodent models of ALS and SCI.

Amyotrophic Lateral Sclerosis ve Travmatik Spinal Kord Yaralanması Servikal Ventral Horn Hedefleme intraspinal Hücre Transplantasyonu

Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) ...

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

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

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

Sıçanlarda Spinal Kord Yaralanma sonrası Akut ve Kronik Dokunsal Duyu Testi

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

A Contusion Model of Severe Spinal Cord Injury in Rats

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

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

Sıçanlarda Şiddetli Spinal Kord Yaralanması bir bere modeli

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

Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis

The split hand phenomenon refers to predominant wasting of thenar muscles and is an early and specific feature of amyotrophic lateral sclerosis (ALS). A novel split hand index (SI) was developed to quantify the split hand phenomenon, and its diagnostic utility was assessed in ALS patients. The split hand index was derived by dividing the product of the compound muscle action potential (CMAP) amplitude recorded over the abductor pollicis brevis and first dorsal interosseous muscles by the CMAP amplitude recorded over the abductor digiti minimi muscle. In order to assess the diagnostic utility of the split hand index, ALS patients were prospectively assessed and their results were compared to neuromuscular disorder patients. The split hand index was significantly reduced in ALS when compared to neuromuscular disorder patients (P&#60;0.0001). Limb-onset ALS patients exhibited the greatest reduction in the split&#160;hand index, and a value of 5.2 or less reliably differentiated ALS from other neuromuscular disorders. Consequently, the split&#160;hand index appears to be a novel diagnostic biomarker for ALS, perhaps facilitating an earlier diagnosis.

Dissociated atrophy of intrinsic hand muscles, termed the split hand, appears to be a specific feature of amyotrophic lateral sclerosis (ALS).&#160;Consequently, a novel neurodiagnostic test, termed the split hand&#160;index, was developed to quantify the clinical phenomenon of the split hand, which differentiated ALS from mimic disorders.

Amyotrofik Lateral Skleroz Tanısında Disosiye ıntrinsic El kas Atrofi Utility

The split hand phenomenon refers to predominant wasting of thenar muscles and is an early and specific feature of amyotrophic lateral sclerosis (ALS). A ...

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, ...

A Radio-telemetric System to Monitor Cardiovascular Function in Rats with Spinal Cord Transection and Embryonic Neural Stem Cell Grafts

High thoracic or cervical spinal cord injury (SCI) can lead to cardiovascular dysfunction. To monitor cardiovascular parameters, we implanted a catheter connected to a radio transmitter into the femoral artery of rats that underwent a T4 spinal cord transection with or without grafting of embryonic brainstem-derived neural stem cells expressing green fluorescent protein. Compared to other methods such as cannula insertion or tail-cuff, telemetry is advantageous to continuously monitor blood pressure and heart rate in freely moving animals. It is also capable of long term multiple data acquisitions. In spinal cord injured rats, basal cardiovascular data under unrestrained condition and autonomic dysreflexia in response to colorectal distension were successfully recorded. In addition, cardiovascular parameters before and after SCI can be compared in the same rat if a transmitter is implanted before a spinal cord transection. One limitation of the described telemetry procedure is that implantation in the femoral artery may influence the blood supply to the ipsilateral hindlimb.

We present a protocol for using a radio-telemetric system to record cardiovascular parameters in T4 spinal cord transected rats eight weeks after embryonic brainstem neural stem cell grafting into the lesion site. Telemetry is an advanced technique to accurately evaluate cardiovascular function in conscious freely moving spinal cord injured rats.

A Radyo-telemetrik Sistemi Omurilik transeksiyonu ve Embriyonik Nöral Hücre Greftler Kök Sıçanlarda Kardiyovasküler Fonksiyonu Monitör

High thoracic or cervical spinal cord injury (SCI) can lead to cardiovascular dysfunction. To monitor cardiovascular parameters, we implanted a catheter ...

Calibrated Forceps Model of Spinal Cord Compression Injury

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The calibrated forceps model of compression injury is a convenient, low cost, and very reproducible animal model for SCI. We used a pair of modified forceps in accordance with the method published by Plemel et al. (2008) to laterally compress the spinal cord to a distance of 0.35 mm. In this video, we will demonstrate a dorsal laminectomy to expose the spinal cord, followed by compression of the spinal cord with the modified forceps. In the video, we will also address issues related to the care of paraplegic laboratory animals. This injury model produces mice that exhibit impairment in sensation, as well as impaired hindlimb locomotor function. Furthermore, this method of injury produces consistent aberrations in the pathology of the SCI, as determined by immunohistochemical methods. After watching this video, viewers should be able to determine the necessary supplies and methods for producing SCI of various severities in the mouse for studies on SCI and/or treatments designed to mitigate impairment after injury.

Spinal cord injury models should be highly reproducible. We demonstrate that the calibrated forceps compression model of spinal cord injury is an easy to use surgical method for generating reproducible injuries to the murine spinal cord.

Omurilik Sıkıştırma Yaralanma Kalibre Forseps Modeli

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The ...

A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening protocol, demonstrated in video herein, which reliably assesses the neuromuscular function of SOD1-G93A mice in a quick manner. This protocol encompasses a simple neurological scoring system (NeuroScore) designed to assess hindlimb function. NeuroScore is focused on hindlimb function because hindlimb deficits are the earliest reported neurological sign of disease in SOD1-G93A mice. The protocol developed by ALS TDI provides an unbiased assessment of onset of paresis (slight or partial paralysis), progression and severity of paralysis and it is sensitive enough to identify drug-induced changes in disease progression. In this report, the combination of a detailed manuscript with video minimizes scoring ambiguities and inter-experimenter variability thus allowing for the protocol to be adopted by other laboratories and enabling comparisons between studies taking place at different settings. We believe that this video protocol can serve as an excellent training tool for present and future ALS researchers.

This video protocol describes a sensitive, reliable, and quick method for evaluating the neuromuscular deficits in a transgenic mouse model of amyotrophic lateral sclerosis.

ALS SOD1-G93A Fare Modeli hastalığın ilerlemesine değerlendirilmesi için Hızlı Fenotipik Nörolojik Puanlama Sistemi

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening ...

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 ...