We are supported by research grants from the National Natural Science Foundation of China (NO. 81400590), National Institutes of Health (U54 CA156735) and Takeda Pharmaceutical Company Ltd. (MA-NC-D-156).

Tüm hayvan deneyleri Kurumsal Hayvan Bakım ve Kullanım Kurulu tarafından onaylanmıştır. 1. Fare Hazırlık <ol><li> Üzerinde fareler kullanın ~ vücut ağırlığı 20 g veya ameliyat yaşı 6 ~ yukarıdaki hafta. </li><li> Ameliyattan önce, fareler laboratuvar yemi ve su ad libitum beslendi ve 00:12 saat ışık-karanlık çevrimi ile korumak. </li><li> Saç kesme makinesi ile cerrahi alan tıraş. 80 mg / kg ketamin ve 12 mg / kg ksilazin intraperitonal enjeksiyonu ile fareler anestezi. Bu doz birkaç dakika içinde uykuya fareler koyar ve aşağıdaki cerrahi işlemler için yeterli anestezi sağlar. </li><li> Ayak tabanı sıkışmak zaman kornea refleksi ve uzuv retraksiyon yokluğunda dayalı doğru anesthetization onaylayın. Kuruluğunu önlemek için gözleri oftalmik merhem yağlama uygulayın. </li><li> Betadine solüsyonu ile cilt sterilize edin. </li></ol> 2. Mide cezir modeli (Şekil 1B) <ol><li> Bir üst yapanüs işaret kılıç şeklinde başlayarak ~ 2 cm orta hat insizyonu. </li><li> Orta hat boyunca karın boşluğu açın. Bir makas ile poz geliştirmek için kılıç şeklinde çıkarın. </li><li> Ayrı ve karaciğer ve mide arasında bağ dokuları kesmek. Bağlanır ve sipariş fundus kadar tamamen ücretsiz olarak dalak ve fundus arasındaki damar demeti kesti. </li><li> Sola hafifçe fundus çevirin ve bu alandaki gastroözofageal bileşke sol tarafını ortaya çıkarmak. Epitel maruz keskin bir makas kullanarak uzak yemek borusunda boyunca kas üzerinde 5 mm boyuna kesi yapmak. </li><li> Aynı yönde (kesi 1, Şekil 1B) boyunca epitel açın kesin. (Kesi 2, 3 ve 4, Şekil 1B) keskin bir işletim makas ile mide çoğu kesmek için mide üç kesiler olun. Mide boş değilse, dikkatli gastrik içeriğini kaldırmak. </li><li> Bir 8-0 prolen sutu koyunYeniden doğru mukozal ile Noktası üzerinden (mide üzerine) (yemek borusu üzerine) ve Point &#39;(konik noktası iğne ile) muhalefet mukozal. Sırasıyla Nokta b ve b Nokta &#39;, ve Points diğer çiftleri aracılığıyla Aynı şekilde yer dikişler. Eşit olarak, bu dikişler alanı birbirinden 3-4 mm. </li><li> Kan ve mide içeriğini temizlemek için serum fizyolojik ile karın boşluğuna yıkayın. Ipek dikişlerle karın duvarı ve metal klipleri ile cilt kapatın. </li></ol> 3. Karışık Reflü Modeli (Şekil 1C) <ol><li> Takip gastroözofageal kavşak açığa 2.4 2.1 adımları tekrarlayın. </li><li> Yavaşça yemek borusu arkasındaki kan damarlarından özofagus dorsal yüzü ayırın. Özofagus ve kan damarları arasında küçük bir pamuk ucu geçirin. Not: Pamuk kısmen boyutunu azaltmak için ucundan çıkarılabilir. Bu pamuk uçlu yemek borusu yukarı kaldırarak ve kan damarlarını korur iki amaca hizmet eder. </li><li> İki 5 mm boyuna inc olungastroözofageal bileşke ve keskin işletim makas ile pilor komşu duodenum yakın ucunda isions her. Duodenum üzerinde kesi için, kan damarları önlemek ve anti-mezenterik sınırında yer. </li><li> Kesintiye 8-0 Prolen sütür ile muhalefeti mukozal doğru mukozal ile kesiler anastomoz. Genellikle sırt tarafında 3-4 sütür ve ön yüzünde 2-3 sütür koyun. </li><li> Pamuk ucunu sökün. Serum fizyolojik ile karın boşluğuna yıkayın ve karın duvarı ve cilt kapatın. </li></ol> 4. Duodenal Reflü Modeli (Şekil 1D) <ol><li> Karışık reflüyü üretmek için 3.4 3.1 adım izleyin. </li><li> Dikkatle arka tarafını ortaya çıkarmak için mide yukarı kaldırın. Karaciğerin bir lob karaciğer ve mide arkası arasında bağ dokuları tarafından yakalandı olabilir. Dikkatle bağ dokuları kesmek düzgün karaciğeri korumak ve yemek borusu sırt tarafında kan damarları açığa. </li><li> Bağlanır vekan damarlarının kesti. Bağlanır ve gastroözofageal bileşkede özofagus kesti. </li><li> Pilor de duodenum Arter. Bağlanır ve Mezenterium kesti. Bütün mide çıkarın. </li><li> Normal tuzlu su ile karın boşluğuna yıkayın. Karın duvarı ve cilt kapatın. </li></ol> 5. Post-cerrahi tedavi <ol><li> Ameliyat sonrasında, bir ısıtma yastığı ile vücut ısısını korumak. Sadece sternal yatma kavuştuktan sonra, geri diğer hayvanlar ile fareler yerleştirin. </li><li> Enfeksiyonu önlemek ve ağrıyı hafifletmek için antibiyotik ve analjezik verin. Baytril enjekte (10 mg / kg, ip, qd, 3 gün boyunca) enfeksiyonu önlemek ve Buprenorfin hidroklorür için (0.05 mg / kg, sc, teklif. Iki gündür) ağrı kesici olarak. Açlık ameliyat sonrası gerekli değildir. Sıvı veya yumuşak bir diyet verilebilir. </li><li> Fareler aşağıdaki belirtileri göstermeye günlük BAZDA genel sağlık durumunu (dramatik kilo kaybı&gt;% 15, app eksikliği değerlendirinetite, seslendirme, fareler euthanize, ağız, burun veya gözler, kambur jest, hareketsizlik, anormal tımar aktivitesi) dan boşaltın. </li></ol>

<ol>
	<li>Kandulski, A., Malfertheiner, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gastroesophageal+reflux+disease--from+reflux+episodes+to+mucosal+inflammation.">Gastroesophageal reflux disease--from reflux episodes to mucosal inflammation.</a> Nat Rev Gastroenterol Hepatol. 9 (1), 15-22 (2012).</li><li>Orlando, R. 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+integrity+of+the+esophageal+mucosa.+Balance+between+offensive+and+defensive+mechanisms.">The integrity of the esophageal mucosa. Balance between offensive and defensive mechanisms.</a> Best Pract Res Clin Gastroenterol. 24 (6), 873-882 (2010).</li><li>Stairs, D. B., Kong, J., Lynch, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cdx+genes,+inflammation,+and+the+pathogenesis+of+intestinal+metaplasia.">Cdx genes, inflammation, and the pathogenesis of intestinal metaplasia.</a> Prog Mol Biol Transl Sci. 96, 231-270 (2010).</li><li>Spechler, S. J., Fitzgerald, R. C., Prasad, G. A., History Wang, K. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=molecular+mechanisms,+and+endoscopic+treatment+of+Barrett's+esophagus.">molecular mechanisms, and endoscopic treatment of Barrett's esophagus.</a> Gastroenterology. 138 (3), 854-869 (2010).</li><li>Fang, Y., 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=Cellular+origins+and+molecular+mechanisms+of+Barrett's+esophagus+and+esophageal+adenocarcinoma.">Cellular origins and molecular mechanisms of Barrett's esophagus and esophageal adenocarcinoma.</a> Ann N Y Acad Sci. 1300, 187-199 (2013).</li><li>Garman, K. S., Orlando, R. C., Chen, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Review:+Experimental+models+for+Barrett's+esophagus+and+esophageal+adenocarcinoma.">Review: Experimental models for Barrett's esophagus and esophageal adenocarcinoma.</a> Am J Physiol Gastrointest Liver Physiol. 302 (11), G1231-G1243 (2012).</li><li>Baruah, 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=Translational+research+on+Barrett's+esophagus.">Translational research on Barrett's esophagus.</a> Ann N Y Acad Sci. 1325, 170-186 (2014).</li><li>Lechpammer, 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=Flavopiridol+reduces+malignant+transformation+of+the+esophageal+mucosa+in+p27+knockout+mice.">Flavopiridol reduces malignant transformation of the esophageal mucosa in p27 knockout mice.</a> Oncogene. 24 (10), 1683-1688 (2005).</li><li>Hao, J., Liu, B., Yang, C. S., Chen, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gastroesophageal+reflux+leads+to+esophageal+cancer+in+a+surgical+model+with+mice.">Gastroesophageal reflux leads to esophageal cancer in a surgical model with mice.</a> BMC Gastroenterol. 9, 59 (2009).</li><li>Mari, 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=A+pSMAD/CDX2+complex+is+essential+for+the+intestinalization+of+epithelial+metaplasia.">A pSMAD/CDX2 complex is essential for the intestinalization of epithelial metaplasia.</a> Cell Rep. 7 (4), 1197-1210 (2014).</li><li>Fang, Y., 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=Gastroesophageal+reflux+activates+the+NF-kappaB+pathway+and+impairs+esophageal+barrier+function+in+mice.">Gastroesophageal reflux activates the NF-kappaB pathway and impairs esophageal barrier function in mice.</a> Am J Physiol Gastrointest Liver Physiol. 305 (1), G58-G65 (2013).</li><li>Chen, H., 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=Nrf2+deficiency+impairs+the+barrier+function+of+mouse+oesophageal+epithelium.">Nrf2 deficiency impairs the barrier function of mouse oesophageal epithelium.</a> Gut. 63 (5), 711-719 (2014).</li></ol>

One of the authors (XC) received funding that was provided by Takeda Pharmaceutical Company Ltd which supports basic research associated with gastroesophageal reflux disease. None of the reagents or instruments used in this article is produced by this company.

Çeşitli cerrahi modeller kemiricilerde mide, duodenum ve karışık reflüyü taklit etmek kurulmuştur. Burada tarif edilen bu üç prosedür sonrası hayatta kalma makul fiyatlar ile uzun süreli deneyler için de uygundur. Cerrahi deneyime sahip bir araştırmacı uygulama kısa bir süre sonra teknik kavramak gerekir. Kanama cerrahi, karaciğer, mide, ve kan damarlarının yanlışlıkla zarar arasında bağ dokularının ayrılması sırasında karaciğer laserasyon önce anestezik in...

Gastroesophageal reflux disease (GERD) is a chronic disorder caused by the prolonged exposure of distal esophagus to gastric or gastroduodenal contents1. Prolonged exposure to these noxious refluxates impairs the intrinsic defenses within the esophageal epithelium and thus results in esophagitis2. Barrett&#8217;s esophagus arises in the setting of chronic reflux, and is a premalignant lesion with increased risk of esophageal adenocarcinoma3,4. Despite the clinical importance, the mechanisms of GERD, Barrett&#8217;s esophagus and adenocarcinoma have not been well understood. 
Animal models are essential for research on etiology, pathology, molecular mechanisms, prevention and treatment of human diseases. Up to date, various animal models of GERD, Barrett&#8217;s esophagus and adenocarcinoma have been developed using model animals5,6. Mouse esophagus is lined with stratified squamous epithelium which is histologically similar to that in human esophagus. Although a mouse esophagus is different from human esophagus in terms of keratinization and the absence of submucosal glands, the mouse is still an appealing model animal because of its relatively low cost of maintenance and its potential of sophisticated genetic modifications. Two approaches are commonly used to model GERD, Barrett&#8217;s esophagus and adenocarcinoma in mice: reflux surgery and genetic modification. Reflux surgery is the best way to induce reflux and genetic modifications mimics molecular alterations5,7. Reflux surgery can be combined with genetic modifications to further understand disease mechanisms8. 
Many surgical procedures have been reported by us and others6,9: (1) gastric reflux: pyloric ligation, pyloric constriction with forestomach ligation, Wendel cardioplasty, and esophagogastric anastomosis; (2) mixed reflux: esophagogastroduodenal anastomosis, esophagoduodenostomy (or esophagojejunostomy); (3) duodenal reflux: esophagogastroduodenal anastomosis plus gastrectomy; (4) reflux of chemical components: bilious reflux, pancreatic reflux, esophageal perfusion; and (5) esophageal transplantation5. Recently a microsurgical mouse model was reported to produce jejunal reflux via an esophagojejunostomy with magnets10. These surgical models have advantages over in vitro cell culture or organotypic culture models. In vitro, esophageal cells cannot tolerate a medium with high acidity or high concentrations of bile acids. Unconjugated bile acids which are commonly used to produce changes in esophageal epithelial cells in vitro are usually not present in the duodenal refluxate in vivo. Thus conclusions drawn from such in vitro studies should be taken with caution.
Surgery on the mouse esophagus remains a technical challenge because of its small size. A low rate of postoperative survival does not allow experiments which require certain sample size to reach statistically sound conclusions. In the past we have successfully developed and characterized surgical models of gastric reflux, mixed reflux, duodenal reflux with mice in long-term experiments9,11,12. We have also provided consultation to several other groups in their mouse surgery. Herein, we describe three surgical procedures in mice in order to help the community to establish these models in their labs.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Instruments</td>
			<td>Source</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Dumont #1 Forceps Dumostar Tip&#160;</td>
			<td>Roboz Surgical Instrument Co. (Gaithersburg, MD)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Micro Clip Applying Forceps 5.5&#34;</td>
			<td>Roboz Surgical Instrument Co. (Gaithersburg, MD)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Bonn Scissors 3.5&#34; Straight 15mm Sharp/Sharp Tungsten Carbide Blades</td>
			<td>Roboz Surgical Instrument Co. (Gaithersburg, MD)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Operating Scissors 5.5&#34; Straight Sharp/Sharp SureCut</td>
			<td>Roboz Surgical Instrument Co. (Gaithersburg, MD)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>4-0 Silk Black Braid 100 Yard Spool</td>
			<td>Roboz Surgical Instrument Co. (Gaithersburg, MD)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Surgeon&#39;s Needle 1/2 Circle Cutting Edge Size 12 (25 mm Chord Length) Pack 12</td>
			<td>Roboz Surgical Instrument Co. (Gaithersburg, MD)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Halsey Needle Holder 5&#34; Smooth</td>
			<td>Roboz Surgical Instrument Co. (Gaithersburg, MD)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Micro Needle Holder 5.125&#34; Curved Lock .6mm</td>
			<td>Roboz Surgical Instrument Co. (Gaithersburg, MD)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Reflex 9mm Wound Clip Applier</td>
			<td>Roboz Surgical Instrument Co. (Gaithersburg, MD)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Reflex 9mm Wound Clips Box Of 100</td>
			<td>Roboz Surgical Instrument Co. (Gaithersburg, MD)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PRONOVA Poly (hexafluoropropylene-VDF) Suture 8-0</td>
			<td>Ethicon US, LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Reagents</td>
			<td>Source</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Ringer&#39;s solution</td>
			<td>Henry Schein, Inc.</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>ketamine</td>
			<td>Henry Schein, Inc.</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>xylazine</td>
			<td>Henry Schein, Inc.</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

surgical models of gastroesophageal reflux with mice

Multiple surgical procedures have been reported to induce gastroesophageal reflux in animals. Herein, we report three surgical models with mice aiming to induce reflux of gastric contents, duodenal contents or mixed contents. Surgical procedures and general principles have been described in detail. A researcher with surgical experience should be able to grasp the technique after a short period of practice. After surgery, most mice can survive and develop reflux esophagitis similar to that in humans. However, it should be noted that histological differences between mouse and human esophagus are the inherent limitations of these surgical models. If used for research on Barrett&#8217;s esophagus and adenocarcinoma, these procedures may need to be combined with genetic modifications.

Çoğu fareler (&gt;% 95) ameliyat yaşayabilir. Perioperatif dönemde, önde gelen ölüm nedenleri anestezik dozda, kanama ve bilinmeyen nedenler sayılabilir. Ameliyattan sonra dört hafta,&gt; duodenal reflü mide reflü ya da karışık reflü ve&gt;% 80 farelerin% 90 fareler yaşayabilir. Bu dönemde, fareler başta özofagus darlığı ve yemek için yetersizlik ölmektedir. Bu fareler ağır stres (kambur duruş, hareketsizlik, kusma, batık gözler, seslendirme, vs.) belirt...

Watch this Scientific Journal Video about Surgical Models of Gastroesophageal Reflux with Mice at JoVE.com

Surgical Models of Gastroesophageal Reflux with Mice

This article demonstrates surgical procedures of gastroesophageal reflux with mice. These models are useful tools for research on mechanisms and treatment of gastroesophageal reflux disease and potentially Barrett&#8217;s esophagus and esophageal adenocarcinoma.

Fare ile Gastroözofageal Reflü Cerrahi Modelleri

Multiple surgical procedures have been reported to induce gastroesophageal reflux in animals. Herein, we report three surgical models with mice aiming to ...

surgical-models-of-gastroesophageal-reflux-with-mice

Research

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Medicine

10.0K Görüntüleme.  Ningxia Medical University General Hospital. This article demonstrates surgical procedures of gastroesophageal reflux with mice. These models are useful tools for research on mechanisms and treatment of gastroesophageal reflux disease and potentially Barrett’s esophagus and esophageal adenocarcinoma.

Video: Surgical Models of Gastroesophageal Reflux with Mice

Surgical Management of Meatal Stenosis with Meatoplasty

Meatal stenosis is a common urologic complication after circumcision. Children present to their primary care physicians with complaints of deviated urinary stream, difficult-to-aim, painful urination, and urinary frequency. Clinical exam reveals a pinpoint meatus and if the child is asked to urinate, he will usually have an upward, thin, occasionally forceful urinary stream with incomplete bladder emptying. The mainstay of management is meatoplasty (reconstruction of the distal urethra /meatus). This educational video will demonstrate how this is performed.

Meatoplasty, surgical management of meatal stenosis.

Meatoplasty meatal stenoz Cerrahi Yönetim

Meatal stenosis is a common urologic complication after circumcision.  Children present to their primary care physicians with complaints of deviated ...

Tıp

Implantation of Radiotelemetry Transmitters Yielding Data on ECG, Heart Rate, Core Body Temperature and Activity in Free-moving Laboratory Mice

The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a manageable size and relatively easy to house. These factors, together with the availability of a wealth of spontaneous and experimentally induced mutants, make laboratory mice ideally suited to a wide variety of research areas.
In cardiovascular, pharmacological and toxicological research, accurate measurement of parameters relating to the circulatory system of laboratory animals is often required. Determination of heart rate, heart rate variability, and duration of PQ and QT intervals are based on electrocardiogram (ECG) recordings. However, obtaining reliable ECG curves as well as physiological data such as core body temperature in mice can be difficult using conventional measurement techniques, which require connecting sensors and lead wires to a restrained, tethered, or even anaesthetized animal. Data obtained in this fashion must be interpreted with caution, as it is well known that restraining and anesthesia can have a major artifactual influence on physiological parameters1, 2.
Radiotelemetry enables data to be collected from conscious and untethered animals. Measurements can be conducted even in freely moving animals, and without requiring the investigator to be in the proximity of the animal. Thus, known sources of artifacts are avoided, and accurate and reliable measurements are assured. This methodology also reduces interanimal variability, thus reducing the number of animals used, rendering this technology the most humane method of monitoring physiological parameters in laboratory animals3, 4. Constant advancements in data acquisition technology and implant miniaturization mean that it is now possible to record physiological parameters and locomotor activity continuously and in realtime over longer periods such as hours, days or even weeks3, 5.
Here, we describe a surgical technique for implantation of a commercially available telemetry transmitter used for continuous measurements of core body temperature, locomotor activity and biopotential (i.e. onelead ECG), from which heart rate, heart rate variability, and PQ and QT intervals can be established in freeroaming, untethered mice. We also present pre-operative procedures and protocols for post-operative intensive care and pain treatment that improve recovery, well-being and survival rates in implanted mice5, 6.

A surgical technique for implantation of commercially available telemetry transmitters used for continuous measurement of biopotential (one-lead ECG), heart rate, core body temperature and locomotor activity in freely moving mice is shown. Recommendations and protocols for post-operative care and pain relief, improving recovery, well being and survival rate are also presented.

EKG, Nabız, Core Vücut Sıcaklığı ve Serbest hareket eden Laboratuar Fare Etkinlik Veri Verimli Radiotelemetry Vericiler implantasyonu

The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a ...

Minimal Invasive Surgical Procedure of Inducing Myocardial Infarction in Mice

Myocardial infarction still remains the main cause of death in western countries, despite considerable progress in the stent development area in the last decades. For clarification of the underlying mechanisms and the development of new therapeutic strategies, the availability of valid animal models are mandatory. Since we need new insights into pathomechanisms of cardiovascular diseases under in vivo conditions to combat myocardial infarction, the validity of the animal model is a crucial aspect. However, protection of animals are highly relevant in this context. Therefore, we establish a minimally invasive and simple model of myocardial infarction in mice, which assures a high reproducibility and survival rate of animals. Thus, this models fulfils the requirements of the 3R principle (Replacement, Refinement and Reduction) for animal experiments and assure the scientific information needed for further developing of therapeutical strategies for cardiovascular diseases.

A highly reproducible model for myocardial infarction in mice with minimal invasive manipulations is described. The model can be easily performed, resulting in a high reproducibility and survival rate. Thus, the described model will reduce the number of required animals as requested by the 3R principle (Replacement, Refinement and Reduction).

Farelerde Miyokard İnfarktüsü Oluşturan Minimal İnvaziv Cerrahi Prosedür

Myocardial infarction still remains the main cause of death in western countries, despite considerable progress in the stent development area in the last ...

Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including Parkinson's and Huntington's can disrupt it. People with Parkinson's disease, for example, tend to have increased saccadic latencies. Consequently, the quantitative measurement of saccadic eye movements has received considerable attention as a potential biomarker for neurodegenerative conditions. A lot more can be learned about the brain in both health and disease by observing what happens to eye movements when the function of specific brain areas is perturbed. Deep brain stimulation is a surgical intervention used for the management of a range of neurological conditions including Parkinson's disease, in which stimulating electrodes are placed in specific brain areas including several sites in the basal ganglia. Eye movement measurements can then be made with the stimulator systems both off and on and the results compared. With suitable experimental design, this approach can be used to study the pathophysiology of the disease being treated, the mechanism by which DBS exerts it beneficial effects, and even aspects of normal neurophysiology.

This paper describes the use of quantitative measurement of eye movements in conjunction with stimulation of focal areas of the deep brain in order to study physiology, pathophysiology, and the mechanisms of deep brain stimulation.

Derin Beyin Uyarım ile Saccadometry kullanarak normal ve patolojik beyin fonksiyonlarını incelemek için

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including ...

Cutaneous Surgical Denervation:  A Method for Testing the Requirement for Nerves in Mouse Models of Skin Disease

Cutaneous somatosensory nerves function to detect diverse stimuli that act upon the skin. In addition to their established sensory roles, recent studies have suggested that nerves may also modulate skin disorders including atopic dermatitis, psoriasis and cancer. Here, we describe protocols for testing the requirement for nerves in maintaining a cutaneous mechanosensory organ, the touch dome (TD). Specifically, we discuss methods for genetically labeling, harvesting and visualizing TDs by whole-mount staining, and for performing unilateral surgical denervation on mouse dorsal back skin. Together, these approaches can be used to directly compare TD morphology and gene expression in denervated as well as sham-operated skin from the same animal. These methods can also be readily adapted to examine the requirement for nerves in mouse models of skin pathology. Finally, the ability to repeatedly sample the skin provides an opportunity to monitor disease progression at different stages and times after initiation.

This article includes detailed protocols for genetic labeling of mouse skin, surgical denervation, skin biopsy and visualizing labeled epithelia by whole-mount &#946;-galactosidase staining. These methods can be used to test the requirement for nerves in mouse models of normal and pathological skin.

Deri Cerrahi denervasyon: Cilt Hastalıkları Fare modelleri Sinirler için Gereği Test Bir Yöntem

Cutaneous somatosensory nerves function to detect diverse stimuli that act upon the skin. In addition to their established sensory roles, recent studies ...

Intravital Microscopy of Tumor-associated Vasculature Using Advanced Dorsal Skinfold Window Chambers on Transgenic Fluorescent Mice

Tumor and tumor vessel development, as well as tumor response to therapeutics, are highly dynamic biological processes. Histology provides static information and is often not sufficient for a correct interpretation. Intravital evaluation, in which a process is followed in time, provides extra and often unexpected information. With the creation of transgenic animals expressing cell-specific markers and live cell tracers, improvements to imaging equipment, and the development of several imaging chambers, intravital microscopy has become an important tool to better understand biological processes. This paper describes an experimental design for the investigation of tumor vessel development and of therapeutic effects in a spatial and temporal manner. Using this setup, the stage of vessel development, tip cell and lumen formation, blood flow, extravasation, an established vascular bed, and vascular destruction can be visualized and followed. Furthermore, therapeutic effects, intratumoral fate, and the localization of chemotherapeutic compounds can also be followed.

This protocol describes the intravital imaging of transgenic mice expressing cell-specific fluorescent markers. Intravital imaging provides a non-invasive method for high-resolution observations in living animals using implantable windows through which the microscopic visualization of processes is possible. This method is especially useful to study longitudinal processes.

Tümör ilişkili damarlara kullanmanın intravital mikroskobu gelişmiş Dorsal deri kıvrım pencere Chambers transgenik floresan fareler üzerinde

Tumor and tumor vessel development, as well as tumor response to therapeutics, are highly dynamic biological processes. Histology provides static ...

Sleeve Gastrectomy in Mice using Surgical Clips

The number of people who are overweight and obese is continually increasing both in the adult and adolescent populations. This coincides with the increased universal phenomenon of type 2 diabetes (T2D) and other metabolic problems. Bariatric surgery, such as SG, is currently one of the most effective and commonly used long-term treatment for obesity and T2D, but the association between them is not completely explored yet. The mechanisms underlying the outcomes seen after bariatric surgery in humans can be investigated based on preclinical animal studies. The SG reduces body weight, glucose levels and many metabolic parameters, and is easy to perform with a low incidence of complications. The goal of this work is to provide a simple method and an uncomplicated preclinical model of bariatric surgery in animals for researchers.

The prevalence of diabetes and obesity is continuously increasing worldwide. The mechanisms between diabetes, obesity and their associated mortality and co-morbidities need to be further investigated. Here, we present a protocol for sleeve gastrectomy (SG) in animals as an uncomplicated preclinical model of bariatric surgery.

Cerrahi Klipsler Kullanılarak Farelerde Sleeve Gastrektomi

The number of people who are overweight and obese is continually increasing both in the adult and adolescent populations. This coincides with the ...

Vacuum-Sealed Hot Water Bath Immersion for the Preparation of Anatomical and Surgical Cadaveric Bone Models

Bone models serve many purposes, including improving anatomical understanding, preoperative surgical planning, and intraoperative referencing. Several techniques for the maceration of soft tissues have been described, mainly for forensic analysis. For clinical research and medical use, these methods have been superseded by three-dimensional (3D) printed models, which require substantial equipment and expertise, and are costly. Here, cadaveric sheep vertebral bone was cleaned by vacuum sealing the specimen with commercial dishwashing detergent, immersing in a hot water bath, and subsequently manually removing the soft tissue. This eliminated the disadvantages of the previously existing maceration methods, such as the existence of foul odors, usage of hazardous chemicals, substantial equipment, and high costs. The described technique produced clean, dry samples while maintaining anatomical detail and structure to accurately model the osseous structures that can be useful for preoperative planning and intraoperative referencing. The method is simple, low-cost, and effective for bone model preparation for education and surgical planning in veterinary and human medicine.

The present protocol describes the maceration and cleaning of cadaveric bone with a vacuum-sealed, hot water bath immersion technique. This is a low-cost, safe, and effective method to produce anatomical specimens for surgical planning and medical education as an alternative to three-dimensional (3D) printed models.

Anatomik ve cerrahi kadavra kemik modellerinin hazırlanması için vakumla kapatılmış sıcak su banyosuna daldırma

Bone models serve many purposes, including improving anatomical understanding, preoperative surgical planning, and intraoperative referencing. Several ...

Surgical Procedure for Intrapulmonary Tracheal Transplantation in Mice

Farelerde İntrapulmoner Trakeal Transplantasyon için Cerrahi Prosedür

<meta charset="utf8"></head><body>Sıçanlarda Serebral İskemik Komayı İndüklemek için Tek Adımlı Cerrahi

Cerebral Ischemic Coma Model Induced by Modified Four-Vessel Occlusion

Coma caused by cerebral ischemia is the most serious complication of cerebral ischemia. Four-vessel occlusion can establish a cerebral ischemic coma model for disease research and drug development. However, the commonly used four-vessel occlusion method mainly involves inserting an electrocoagulation pen into the bilateral pterygoid foramen of the first cervical vertebra behind the neck to electrocoagulate the vertebral arteries. This process carries the risk of incomplete electrocoagulation, bleeding, and damage to the brainstem and spinal cord. Twenty-four hours after surgery, re-anesthetized rats undergo carotid artery ligation in front of the neck. Two surgeries expose the rats to a higher risk of infection and increase the experimental period. In this study, during a single surgical procedure, an anterior cervical incision was used to locate the key site where the vertebral artery penetrates the first cervical vertebra. The bilateral vertebral arteries were electrocauterized under visual conditions, while the bilateral common carotid arteries were separated to place loose knots. When the limbs of the rats began twitching, the bilateral common carotid arteries were quickly ligated to induce ischemic coma. This method can avoid the risk of infection caused by two surgical operations and is easy to perform with a high success rate, providing a useful reference for relevant practitioners.

<meta charset="utf8"></head><body>Yazar Spotlight: Basitleştirilmiş Bir Sıçan Modeli ile Serebral İskemi Araştırmalarının Geliştirilmesi

This protocol describes the process for inducing a cerebral ischemic coma model using a modified four-vessel occlusion method.

Modifiye Dört Damar Oklüzyonu ile İndüklenen Serebral İskemik Koma Modeli

Coma caused by cerebral ischemia is the most serious complication of cerebral ischemia. Four-vessel occlusion can establish a cerebral ischemic coma model ...