Todos los métodos aquí descritos han sido aprobados por la autoridad veterinaria (Landesamt für Landwirtschaft, und Lebensmittelsicherheit Fischerei Mecklenburg-Vorpommern, LALLF M-V).
1. preoperatorio cuidado y preparación del Animal
<ol><li>A su llegada a las instalaciones de animales, animales (C57Bl/6) se dividen en grupos de tamaño similar, jaula a cada grupo juntos y mantener constante a lo largo de los experimentos de los grupos. Nota: Utilizar animales del mismo sexo. Los resultados descritos se obtuvieron con ratones machos. Nota: Si se utilizan machos, grupos de jaula juntos a partir de cuando tienen 7 semanas de edad para que pueda establecerse una jerarquía, minimizando así el riesgo de comportamiento agresivo durante los experimentos.</li>
	<li>Por lo menos una semana antes de la cirugía, cambiar a una alta energía (> 14 MJ/kg) y alta en proteínas (> 20%) de la alimentación que contiene todos los oligoelementos esenciales y vitaminas (para detalles, ver lista de materiales). Nota: Asegure todos los ratones pesan al menos 25 g cuando se realiza la cirugía.</li>
	<li>Inducir analgesia y la anestesia por inyección intraperitoneal de ketamina (87 mg/kg i.p.) y el clorhidrato de xilacina (13 mg/kg i.p.). Espere hasta que el ratón tolera la estimulación mecánica, por ejemplo campo de dedo del pie, sin respuesta de motor.</li>
	<li>Asegure el ratón narcotizado con cintas en una posición supina sobre una arpillera de calor colocado en la mesa de operación, garantizando la colocación durante la operación estable y evitando una abrumadora pérdida de calor corporal. Nota: La arpillera de calor debe tener una temperatura de 36 ° C a 40 ° C; la temperatura de la sala de operaciones debe ser de 21 ° C.</li>
</ol>2. distal de la colostomía operación
<ol><li>Afeitarse el vello abdominal. Antes de comenzar la cirugía, desinfectar el campo de la operación tres veces con alcohol 70% y un yodóforo. Cubra el campo de la operación para garantizar condiciones asépticas.</li>
	<li>Realizar una laparotomía mediana 15 mm mediante la incisión de los músculos abdominales y el peritoneo a lo largo de la linea alba, minimizando así la pérdida de sangre.</li>
	<li>Utilizar dos pinzas atraumáticas de DeBakey, tire con cuidado hacia el ciego, íleon terminal y el ascendente y el colon transverso de la cavidad peritoneal. Nota: Tenga cuidado de limitar estrictamente la manipulación mecánica del intestino para evitar daños a las estructuras mesentéricas.</li>
	<li>Identificar el polo cecal, el colon ascendente y el intestino (Figuras 1a y 1b). Nota: La correcta identificación de los dos puntos ascendentes es fundamental para la correcta colocación de la colostomía. En casos donde la anatomía de la región ileocecal es ambigua, identifica a la presencia de placas de Peyer del intestino, y la presencia de heces formadas caracteriza el colon.</li>
	<li>Use una regla para determinar la posición de la futura operación del intestino grueso. Se debe colocar 20 mm distal a la válvula ileocecal para una colostomía distal.</li>
	<li>Hacer una segunda incisión de 3 mm en la pared abdominal en el cuadrante superior derecho. Tire el segmento de colon previamente identificadas a través de esta incisión para formar un círculo, teniendo cuidado de no distorsionar el bucle.</li>
	<li>Pasar con cuidado una cánula i.v. flexible calibre 22 a través del mesocolon. Tenga cuidado para no dañar estructuras vasculares mesentéricas.</li>
	<li>Devolver el intestino a la cavidad peritoneal.</li>
	<li>Fijar ambos extremos del tubo flexible a la piel con puntos simples y sutura reabsorbible (p. ej., polyglactin 910 o polyfil 4-0 1/2 c).</li>
	<li>Antes de cerrar la laparotomía, realice reanimación con líquidos usando una inyección intraperitoneal de solución salina al de 0.9% 0,5 mL.</li>
	<li>Cierre del peritoneo y la capa muscular con una sutura continua usando una sutura reabsorbible (p. ej., polyglactin 910 o polyfil 4-0 1/2 c). Cierre la piel con una sutura continua usando una sutura reabsorbible (p. ej., polyglactin 910 o polyfil 4-0 1 / 2c).</li>
	<li>Abrir el bucle de colon exteriorizado mediante la realización de un corte transversal subtotal con una tijera fina. Evitar toda lesión del mesenterio. Transecto no el colon completamente.</li>
	<li>Fijar cada abertura de colostomía con tres puntadas de espesor total solo al peritoneo y la piel con un monofilamento, suturas absorbibles (p. ej., Polidioxanona o monofilamento 6-0 3/8s). El aferente del lazo, que es una colostomía de final funcional, y el lazo eferente, que es una fístula mucosa, se separan claramente en este punto (figura 1C). Nota: Tiempo de operación debe ser menos de 20 minutos para limitar las pérdidas de fluidos y térmicas.</li>
	<li>Después de terminar la cirugía, desinfectar instrumentos usando una solución de desinfectante libre de aldehídos en un baño de ultrasonidos según las instrucciones del fabricante.</li>
</ol>3. simulacro de operación (Colotomy)
<ol><li>Realice los pasos 1.1. a través de 2.4.</li>
	<li>Utilice una regla para determinar la posición de futuros colotomy. El colotomy debe colocarse a la misma distancia de la válvula ileocecal que la colostomía en el grupo experimental.</li>
	<li>Abra el colon por lo menos dos tercios su circunferencia usando las tijeras finas.</li>
	<li>Cierre colotomy con una sola capa, espesor total interrumpido con un monofilamento, absorbible sutura sutura (por ejemplo, polydioxanone, monofilamento 6-0 3/8s). Nota: Tiempo de operación debe ser menos de 20 minutos para un cirujano experimentado, limitando las pérdidas de fluidos y térmicas.</li>
	<li>Realice los pasos 2.10. , 2.11. y 2.14.</li>
</ol>4. posoperatorio cuidado
<ol><li>Devolver los animales a sus jaulas. Bien templado el ambiente de 37 ° C (por ejemplo, con una lámpara infrarroja) hasta que los ratones son totalmente despiertos. A continuación, mantenga ratones en un ambiente de temperatura y Humedad reguladas (21 ° C; humedad relativa de 30% ± 10%). Permitir el libre acceso a alimentos y agua potable. Para facilitar la absorción de líquidos, proporcionar alimentación animal empapado de agua adicional.</li>
	<li>Inicio de la analgesia postoperatoria mediante la inyección de 0,1 mg/kg corporal peso buprenorfina s.c. cuando los animales muestran respuesta a la estimulación mecánica. Tenga cuidado para evitar depresión respiratoria.</li>
	<li>Suplemento de agua potable con tramadol 1 mg/mL para analgesia continua durante la primera semana postoperatoria.</li>
	<li>Para compensar la ingesta disminuida de líquidos debido a movilidad reducida, suministrar un cojín sólido de beber en la jaula durante la primera semana postoperatoria.</li>
	<li>Pesan los animales y el comportamiento animal puntuación diariamente durante la primera semana, cada dos días durante el resto del primer mes y cada tercer día durante el segundo mes el score de severidad de la enfermedad descrito en Kleinwort et al. 6.</li>
</ol>

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Todos los autores declaran que no tienen intereses que compiten.

El modelo murino de DC presentada en este protocolo fiable reproduce las características histopatológicas de DC humana (p. ej., desarrollo de novo de los folículos linfoides en la submucosa de segmentos de intestino inflamado, cripta acortamiento y reducción de número de células caliciformes). Aparte de esta ventaja, este modelo es inducida por un factor desencadenante muy similar y presenta un curso clínico de moderado a leve gravedad como es el caso de los seres humanos más afectados.
<p c...

En los últimos años, un número considerable de entidades colitis no infecciosa diferentes de las enfermedades clásicas inflamatorias intestinales (EII; ej., enfermedad enfermedad o colitis de Crohn) han caracterizado clínico e histopathologically en seres humanos. Los mecanismos fisiopatológicos principales en el desarrollo de estas formas de colitis no se entienden completamente parcialmente porque son escasos los modelos animales apropiados. Colitis de la diversión es una de estas entidades recientemente descritas. Aunque el término fue acuñado en 1980 por Glotzer1, la descripción inicial de un fenotipo similar fue dada en 1972 por Morson2. La enfermedad se desarrolla en el 50% al 91% de los pacientes con desvío de enterostomía, y su intensidad clínica varía de3,4. Dada la incidencia anual de alrededor de 120.000 pacientes de colostomía en los Estados Unidos de América, esta entidad de la enfermedad constituye un importante problema de salud.
El objetivo general de desarrollar este protocolo era proporcionar un modelo murino de DC que se apoya en un disparador de colitis similar a ése visto en DC humana y que reproduce las principales características histopatológicas de la enfermedad humana. En contraste con otros modelos de colitis murino la inducción de colitis en nuestro modelo no requiere de animales genéticamente modificados (p. ej., ratones transgénicos IL-7, N-cadherin dominante negativo ratones o ratones TGFβ- / - ), la aplicación de la química irritantes sustancias (p. ej., sulfato de dextrano sódico (DSS) - colitis inducida o ácido de trinitrobenceno sulfónico (TNBS) - inducida por colitis) o la transferencia de poblaciones celulares específicas en ratones deficientes inmunes (como en la transferenciaalta CD45RB modelo de colitis) (para una revisión, véase5). En contraste con otros modelos, el sistema inmune intacto nuestro modelo DC permite la evaluación del mecanismo inmunológico involucrado en el desarrollo de CC. La limitación de la inflamación mucosa al segmento intestinal excluido permite la evaluación de su repercusión sobre la inmunidad mucosa en otras partes del tracto gastrointestinal en la homeostasis inmune en otros compartimentos inmunes del tracto intestinal (p. ej. , Parches de Peyer y ganglios mesenteriale) y en la homeostasis inmune de todo el organismo. Por último, nuestro modelo constituye una herramienta apropiada para investigar los mecanismos de control de estímulos inflamatorios locales origina cambios en el ambiente local normal para el microbioma local, así como antígenos alimentarios.

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		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Operation material</td>
			<td style="width:136px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">heat underlay, 6 watt</td>
			<td style="width:136px;">ThermoLux, Witte + Sutor GmbH</td>
			<td style="width:119px;">461265</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Ethanol 70% (with methylethylketon)</td>
			<td style="width:136px;">Pharmacie of the University Hospital Greifswald</td>
			<td style="width:119px;"></td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Wooden applicators, small cotton head onesided, wooden stick, 150 mm length</td>
			<td style="width:136px;">Centramed GmbH, Germany</td>
			<td style="width:119px;">8308370</td>
			<td style="width:167px;">for disinfection of operation field</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Scissor</td>
			<td style="width:136px;">Aesculap (BRAUN)</td>
			<td style="width:119px;">BC064R</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Atraumatic DeBakey forceps</td>
			<td style="width:136px;">Aesculap (BRAUN)</td>
			<td style="width:119px;">OC021R</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Needle holder</td>
			<td style="width:136px;">Aesculap (BRAUN)</td>
			<td style="width:119px;">BM012R</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Vasofix Safety i.v. cannula 22G</td>
			<td style="width:136px;">Braun Melsungen AG, Germany</td>
			<td style="width:119px;">4268091S-01</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">VICRYL Plus 4-0 violet braided; V-5 17 m 1/2c; 70 cm</td>
			<td style="width:136px;">ETHICON, Inc.</td>
			<td style="width:119px;">VCP994H</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">PDS II 6-0 monofil; V-18 13 mm 3/8c; 70 cm</td>
			<td style="width:136px;">ETHICON, Inc.</td>
			<td style="width:119px;">Z991H</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">BD Plastipak 1 mL (Syringes with needle with sterile interior)</td>
			<td style="width:136px;">BD Medical</td>
			<td style="width:119px;">305501</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Triacid-N (N-Dodecylpropan-1,3-diamin)</td>
			<td style="width:136px;">ANTISEPTICA, Germany</td>
			<td style="width:119px;">18824-01</td>
			<td style="width:167px;">disinfection of surgical instruments in ultrasonic bath</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Medications</td>
			<td style="width:136px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">ketamine 10%, 100 mg/mL (ketamine hydrochloride)</td>
			<td style="width:136px;">selectavet, Dr. Otto Fischer GmbH</td>
			<td style="width:119px;">9089.01.00</td>
			<td style="width:167px;">87 mg/kg i.p.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Xylasel, 20 mg/mL (xylazine hydrochloride)</td>
			<td style="width:136px;">selectavet, Dr. Otto Fischer GmbH</td>
			<td style="width:119px;">400300.00.00</td>
			<td style="width:167px;">13 mg/kg i.p.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">NaCl 0.9%</td>
			<td style="width:136px;">Braun Melsungen AG, Germany</td>
			<td style="width:119px;">6697366.00.00</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Buprenovet 0.3 mg/mL (buprenorphine)</td>
			<td style="width:136px;">Bayer, Germany</td>
			<td style="width:119px;">PZN: 01498870</td>
			<td style="width:167px;">0.1 mg/kg s.c.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Tramal Drops, 100 mg/mL (tramadol hydrochloride)</td>
			<td style="width:136px;">Gr&#252;nenthal GmbH, Germany</td>
			<td style="width:119px;">10116838</td>
			<td style="width:167px;">1 mg/mL drinking water</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Ceftriaxon-saar 2 g (ceftriaxone)&#160;</td>
			<td style="width:136px;">Cephasaar GmbH, Germany</td>
			<td style="width:119px;">PZN: 08844252</td>
			<td style="width:167px;">25 mg/kg body weight i.p.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">metronidazole 5 mg/mL</td>
			<td style="width:136px;">Braun Melsungen AG, Germany</td>
			<td style="width:119px;">PZN: 05543515</td>
			<td style="width:167px;">12.5 mg/kg body weight i.p.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Food</td>
			<td style="width:136px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">ssniff M-Z Ereich</td>
			<td style="width:136px;">ssniff, Germany</td>
			<td style="width:119px;">&#160;V1184-3</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Solid Drink Dehyprev Vit BIO, pouches</td>
			<td style="width:136px;">TripleATrading, the Netherlands</td>
			<td style="width:119px;">SDSHPV-75</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Equipment</td>
			<td style="width:136px;"></td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Nikon Eclipse Ci-L</td>
			<td style="width:136px;">Nikon Instruments Europe BV, Germany</td>
			<td style="width:119px;"></td>
			<td>light microscopy</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">VetScan HM 5&#160;</td>
			<td style="width:136px;">Abaxis, USA</td>
			<td style="width:119px;">770-9000</td>
			<td style="width:167px;">Veterinary hematology analyzer of 50 &#181;l venous EDTA-blood</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Bandelin SONOREX (Ultrasonic bath)</td>
			<td style="width:136px;">Bandelin electronics, Germany</td>
			<td style="width:119px;">RK 100 H</td>
			<td style="width:167px;">disinfection of surgical instruments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Software</td>
			<td style="width:136px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;">NIS-Element BR4 software</td>
			<td style="width:136px;">Nikon Instruments Europe BV, Germany</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">GraphPad Prism Version 6</td>
			<td style="width:136px;">GraphPad Software, Inc.</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
	</tbody>
</table>

murine distal colostomy, a novel model of diversion colitis in c57bl/6 mice

Desviación (DC) es una condición clínica frecuente que ocurre en pacientes con segmentos de intestino excluidos de la corriente fecal como resultado de una enterostomía desviar. La etiología de esta enfermedad sigue siendo mal definida pero parece diferir de la de enfermedades de intestino inflamatorias clásicas tales como la enfermedad de Crohn y colitis ulcerosa. Investigaciones encaminadas a descifrar los mecanismos fisiopatológicos principales en el desarrollo de esta enfermedad ha sido gravemente obstaculizado por la falta de un modelo murino. Este protocolo genera un modelo murino de DC que facilita el estudio del papel del sistema inmune y su interacción con el microbioma en el desarrollo de CC. En este modelo utilizando animales C57BL/6, parte distal del colon se excluye de la corriente fecal al crear una colostomía distal, provocando el desarrollo de leve a moderada inflamación en el segmento intestinal excluido y reproducir las lesiones característica distintiva del ser humano DC con una moderada respuesta inflamatoria sistémica. En contraste con el modelo de la rata, hay un gran número de modelos murinos genéticamente en el fondo de C57BL/6. La combinación de estos animales con nuestro modelo permite que las funciones potenciales de individuales citoquinas, quimiocinas y receptores de moléculas bioactivas (e.g., interleukin (IL) -17; IL-10, chemokine CXCL13, chemokine receptores CXCR5 y CCR7 y el receptor de la esfingosina-1-fosfato 4) a evaluarse en la patogenesia de DC. La disponibilidad de tensiones congenic ratón C57BL/6 fondo facilita en gran medida transferencia experimentos para establecer los roles de distintos tipos de células involucrados en la etiología de DC. Finalmente, el modelo ofrece la oportunidad de evaluar la influencia de las intervenciones locales (p. ej., modificación del microbioma local o terapia antiinflamatoria local) de inmunidad mucosa en los segmentos intestinales afectados y no afectados y en homeostasis inmune sistémica.

La cirugía se tolera bien tanto en los grupos de sham (colotomy) y experimental (colostomía). Mortalidad perioperatoria no debe superar el 10% cuando se realiza correctamente la cirugía y perioperative management. En la primera semana postoperatoria, pérdida de peso significativa se observa en los grupos experimentales y simulados. Animales del grupo impostor alcanzan su nadir de peso normalmente hacia el cuarto día postoperatorio, pero se da un día más tarde en el grupo experiment...

Watch this Scientific Journal Video about Murine Distal Colostomy, A Novel Model of Diversion Colitis in C57BL/6 Mice at JoVE.com

Murine Distal Colostomy, A Novel Model of Diversion Colitis in C57BL/6 Mice

Murino colostomía Distal, un modelo novedoso de desvío Colitis en ratones C57BL/6

Murino colostomía distal proporciona un modelo murino para la colitis de la diversión humana, una colitis linfocítica predominante en el segmento de colon excluido de la corriente fecal.

Diversion colitis (DC) is a frequent clinical condition occurring in patients with bowel segments excluded from the fecal stream as a result of a ...

murine-distal-colostomy-novel-model-diversion-colitis-c57bl6

Research

JoVE Journal

Medicine

12.8K vistas.  Universitätsmedizin Greifswald. Murino colostomía distal proporciona un modelo murino para la colitis de la diversión humana, una colitis linfocítica predominante en el segmento de colon excluido de la corriente fecal.

Video: Murine Distal Colostomy, A Novel Model of Diversion Colitis in C57BL/6 Mice

Murine Model of Wound Healing

Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. Impaired wound healing, which occurs in diabetic patients for example, can lead to severe unfavorable outcomes such as amputation. There is, therefore, an increasing impetus to develop novel agents that promote wound repair. The testing of these has been limited to large animal models such as swine, which are often impractical. Mice represent the ideal preclinical model, as they are economical and amenable to genetic manipulation, which allows for mechanistic investigation. However, wound healing in a mouse is fundamentally different to that of humans as it primarily occurs via contraction. Our murine model overcomes this by incorporating a splint around the wound. By splinting the wound, the repair process is then dependent on epithelialization, cellular proliferation and angiogenesis, which closely mirror the biological processes of human wound healing. Whilst requiring consistency and care, this murine model does not involve complicated surgical techniques and allows for the robust testing of promising agents that may, for example, promote angiogenesis or inhibit inflammation. Furthermore, each mouse acts as its own control as two wounds are prepared, enabling the application of both the test compound and the vehicle control on the same animal. In conclusion, we demonstrate a practical, easy-to-learn, and robust model of wound healing, which is comparable to that of humans.

A murine model of cutaneous wound healing that can be used to assess therapeutic compounds in physiological and pathophysiological settings.

Modelo murino de Curación de Heridas

Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. ...

Investigación

Medicina

Flexible Colonoscopy in Mice to Evaluate the Severity of Colitis and Colorectal Tumors Using a Validated Endoscopic Scoring System

The use of modern endoscopy for research purposes has greatly facilitated our understanding of gastrointestinal pathologies. In particular, experimental endoscopy has been highly useful for studies that require repeated assessments in a single laboratory animal, such as those evaluating mechanisms of chronic inflammatory bowel disease and the progression of colorectal cancer. However, the methods used across studies are highly variable. At least three endoscopic scoring systems have been published for murine colitis and published protocols for the assessment of colorectal tumors fail to address the presence of concomitant colonic inflammation. This study develops and validates a reproducible endoscopic scoring system that integrates evaluation of both inflammation and tumors simultaneously. This novel scoring system has three major components: 1) assessment of the extent and severity of colorectal inflammation (based on perianal findings, transparency of the wall, mucosal bleeding, and focal lesions), 2) quantitative recording of tumor lesions (grid map and bar graph), and 3) numerical sorting of clinical cases by their pathological and research relevance based on decimal units with assigned categories of observed lesions and endoscopic complications (decimal identifiers). The video and manuscript presented herein were prepared, following IACUC-approved protocols, to allow investigators to score their own experimental mice using a well-validated and highly reproducible endoscopic methodology, with the system option to differentiate distal from proximal endoscopic colitis (D-PECS).

Over the past few years, new generation endoscopes have emerged as important diagnostic research aids for evaluating murine colitis and colorectal tumors. We present herein a detailed protocol for endoscopic assessment of inflammation and colorectal tumors in mice, as well as a novel scoring system that uses decimal identifiers to document the endoscopic severity of colitis and colorectal tumors.

La colonoscopia flexible en ratones para evaluar la gravedad de la colitis y colorrectal tumores utilizando un sistema validado de puntuación endoscópica

The use of modern endoscopy for research purposes has greatly facilitated our understanding of gastrointestinal pathologies. In particular, experimental ...

A Murine Model of Subarachnoid Hemorrhage

In this video publication a standardized mouse model of subarachnoid hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of Willis perforation (CWp) and proven by intracranial pressure (ICP) monitoring. Thereby a homogenous blood distribution in subarachnoid spaces surrounding the arterial circulation and cerebellar fissures is achieved. Animal physiology is maintained by intubation, mechanical ventilation, and continuous on-line monitoring of various physiological and cardiovascular parameters: body temperature, systemic blood pressure, heart rate, and hemoglobin saturation. Thereby the cerebral perfusion pressure can be tightly monitored resulting in a less variable volume of extravasated blood. This allows a better standardization of endovascular filament perforation in mice and makes the whole model highly reproducible. Thus it is readily available for pharmacological and pathophysiological studies in wild type and genetically altered mice.

A standardized mouse model of subarachnoid hemorrhage by intraluminal Circle of Willis perforation is described. Vessel perforation and subarachnoid bleeding are monitored by intracranial pressure monitoring. In addition various vital parameters are recorded and controlled to maintain physiologic conditions.

Un modelo murino de hemorragia subaracnoidea

In this video publication a standardized mouse model of subarachnoid  hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of  Willis ...

Modeling Stroke in Mice: Permanent Coagulation of the Distal Middle Cerebral Artery

Stroke is the third most common cause of death and a main cause of acquired adult disability in developed countries. Only very limited therapeutical options are available for a small proportion of stroke patients in the acute phase. Current research is intensively searching for novel therapeutic strategies and is increasingly focusing on the sub-acute and chronic phase after stroke because more patients might be eligible for therapeutic interventions in a prolonged time window. These delayed mechanisms include important pathophysiological pathways such as post-stroke inflammation, angiogenesis, neuronal plasticity and regeneration. In order to analyze these mechanisms and to subsequently evaluate novel drug targets, experimental stroke models with clinical relevance, low mortality and high reproducibility are sought after. Moreover, mice are the smallest mammals in which a focal stroke lesion can be induced and for which a broad spectrum of transgenic models are available. Therefore, we describe here the mouse model of transcranial, permanent coagulation of the middle cerebral artery via electrocoagulation distal of the lenticulostriatal arteries, the so-called &#8220;coagulation model&#8221;. The resulting infarct in this model is located mainly in the cortex; the relative infarct volume in relation to brain size corresponds to the majority of human strokes. Moreover, the model fulfills the above-mentioned criteria of reproducibility and low mortality. In this video we demonstrate the surgical methods of stroke induction in the &#8220;coagulation model&#8221; and report histological and functional analysis tools.

Various murine models of middle cerebral artery occlusion (MCAO) are widely used in experimental brain research. Here, we demonstrate the model of transcranial permanent distal MCAO which produces consistent cortical infarction of a size corresponding to damage imposed by the majority of human ischemic strokes.

Carrera Modelado en ratones: Coagulación permanente de la arteria cerebral media Distal

Stroke is the third most common cause of death and a main cause of acquired adult disability in developed countries. Only very limited therapeutical ...

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study model. As the use of mouse models are often a vital step in preclinical drug discovery and drug development1-8, it is necessary to design a system to introduce drugs into mice in a uniform, reproducible manner. Ideally, the system should permit the collection of blood samples at regular intervals over a set time course. The ability to measure drug concentrations by mass-spectrometry, has allowed investigators to follow the changes in plasma drug levels over time in individual mice1, 9, 10. In this study, paclitaxel was introduced into transgenic mice as a continuous arterial infusion over three hours, while blood samples were simultaneously taken by retro-orbital bleeds at set time points. Carotid artery infusions are a potential alternative to jugular vein infusions, when factors such as mammary tumors or other obstructions make jugular infusions impractical. Using this technique, paclitaxel concentrations in plasma and tissue achieved similar levels as compared to jugular infusion. In this tutorial, we will demonstrate how to successfully catheterize the carotid artery by preparing an optimized catheter for the individual mouse model, then show how to insert and secure the catheter into the mouse carotid artery, thread the end of the catheter out through the back of the mouse&#8217;s neck, and hook the mouse to a pump to deliver a controlled rate of drug influx. Multiple low volume retro-orbital bleeds allow for analysis of plasma drug concentrations over time.

This method was developed with the goal of delivering a steady drug solution via the carotid artery, to assess the pharmacokinetics of novel drugs in mouse models.

Infusiones de la arteria carótida para farmacocinéticas y farmacodinámicas Análisis de taxanos en ratones

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

A Simple Critical-sized Femoral Defect Model in Mice

While bone has a remarkable capacity for regeneration, serious bone trauma often results in damage that does not properly heal. In fact, one tenth of all limb bone fractures fail to heal completely due to the extent of the trauma, disease, or age of the patient. Our ability to improve bone regenerative strategies is critically dependent on the ability to mimic serious bone trauma in test animals, but the generation and stabilization of large bone lesions is technically challenging. In most cases, serious long bone trauma is mimicked experimentally by establishing a defect that will not naturally heal. This is achieved by complete removal of a bone segment that is larger than 1.5 times the diameter of the bone cross-section. The bone is then stabilized with a metal implant to maintain proper orientation of the fracture edges and allow for mobility. 
Due to their small size and the fragility of their long bones, establishment of such lesions in mice are beyond the capabilities of most research groups. As such, long bone defect models are confined to rats and larger animals. Nevertheless, mice afford significant research advantages in that they can be genetically modified and bred as immune-compromised strains that do not reject human cells and tissue.
Herein, we demonstrate a technique that facilitates the generation of a segmental defect in mouse femora using standard laboratory and veterinary equipment. With practice, fabrication of the fixation device and surgical implantation is feasible for the majority of trained veterinarians and animal research personnel. Using example data, we also provide methodologies for the quantitative analysis of bone healing for the model.

Animal models are frequently employed to mimic serious bone injury in biomedical research. Due to their small size, establishment of stabilized bone lesions in mice are beyond the capabilities of most research groups. Herein, we describe a simple method for establishing and analyzing experimental femoral defects in mice.

A-crítico tamaño femoral Defecto sencillo modelo en ratones

While bone has a remarkable capacity for regeneration, serious bone trauma often results in damage that does not properly heal. In fact, one tenth of all ...

A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail

The arteriovenous fistula (AVF) still suffers from a high number of failures caused by insufficient remodeling and intimal hyperplasia from which the exact pathophysiology remains unknown. In order to unravel the pathophysiology a murine model of AVF-failure was developed in which the configuration of the anastomosis resembles the preferred situation in the clinical setting. A model was described in which an AVF is created by connecting the venous end of the branch of the external jugular vein to the side of the common carotid artery using interrupted sutures. At a histological level, we observed progressive stenotic intimal lesions in the venous outflow tract that is also seen in failed human AVFs. Although this procedure can be technically challenging due to the small dimensions of the animal, we were able to achieve a surgical success rate of 97% after sufficient training. The key advantage of a murine model is the availability of transgenic animals. In view of the different proposed mechanisms that are responsible for AVF failure, disabling genes that might play a role in vascular remodeling can help us to unravel the complex pathophysiology of AVF failure.

Here we present a murine model of arteriovenous fistula (AVF) failure in which a clinically relevant anastomotic configuration is incorporated. This model can be used to study the pathophysiology and to test possible therapeutic interventions.

Un Modelo Murino novela de fístula arteriovenosa Fallo: El procedimiento quirúrgico en Detalle

The arteriovenous fistula (AVF) still suffers from a high number of failures caused by insufficient remodeling and intimal hyperplasia from which the ...

The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice

Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical and immunological manifestations. Several spontaneous and inducible animal models mirror common components of human disease, including the bm12 transfer model. Upon transfer of bm12 splenocytes or purified CD4 T cells, C57BL/6 mice rapidly develop large frequencies of T follicular helper cells (Tfh), germinal center (GC) B cells, and plasma cells followed by high levels of circulating anti-nuclear antibodies. Since this model utilizes mice on a pure C57BL/6 background, researchers can quickly and easily study disease progression in transgenic or knockout mouse strains in a relatively short period of time. Here we describe protocols for the induction of the model and the quantitation Tfh, GC B cells, and plasma cells by multi-color flow cytometry. Importantly, these protocols can also be used to characterize disease in most mouse models of SLE and identify Tfh, GC B cells, and plasma cells in other disease models.

The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice

The transfer of bm12 lymphocytes into a C57BL/6 recipient is an established model of systemic lupus erythematosus. Here we describe how to initiate disease using this model and how to characterize T follicular helper cells, germinal center B cells and plasma cells by flow cytometry.

El inducible Modelo BM12 del lupus eritematoso sistémico (LES) en ratones C57BL / 6 ratones

Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical and immunological manifestations. Several spontaneous and inducible ...

A Novel Microsurgical Model for Heterotopic, En Bloc Chest Wall, Thymus, and Heart Transplantation in Mice

Exploration of novel strategies in organ transplantation to prolong allograft survival and minimizing the need for long-term maintenance immunosuppression must be pursued. Employing vascularized bone marrow transplantation and co-transplantation of the thymus have shown promise in this regard in various animal models.1-11 Vascularized bone marrow transplantation allows for the uninterrupted transfer of donor bone marrow cells within the preserved donor microenvironment, and the incorporation of thymus tissue with vascularized bone marrow transplantation has shown to increase T-cell chimerism ultimately playing a supportive role in the induction of immune regulation. The combination of solid organ and vascularized composite allotransplantation can uniquely combine these strategies in the form of a novel transplant model. Murine models serve as an excellent paradigm to explore the mechanisms of acute and chronic rejection, chimerism, and tolerance induction, thus providing the foundation to propagate superior allograft survival strategies for larger animal models and future clinical application. Herein, we developed a novel heterotopic en bloc chest wall, thymus, and heart transplant model in mice using a cervical non-suture cuff technique. The experience in syngeneic and allogeneic transplant settings is described for future broader immunological investigations via an instructional manuscript and video supplement.

To study combined solid organ and vascularized composite allotransplantation, we describe a novel heterotopic en bloc chest wall, thymus, and heart transplant model in mice using a cervical non-suture cuff technique.

Un microquirúrgica Modelo Novela de heterotópico, en bloque, pared torácica, el timo y el trasplante cardiaco en ratones

Exploration of novel strategies in organ transplantation to prolong allograft survival and minimizing the need for long-term maintenance immunosuppression ...

Induction of Accelerated Atherosclerosis in Mice: The "Wire-Injury" Model

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. Moreover, by rupture of the defective vascular wall, atherosclerosis induces occlusive thrombus formation, which represents the main cause of myocardial infarction or stroke and the most frequent cause of death. Despite the advances in the cardiovascular field, many questions remain unanswered, and additional basic research is essential to improve our understanding of the molecular mechanisms during atherosclerosis and its effects. Due to limited clinical studies, there is a need for representative animal models recreating atherosclerotic conditions such as neointima formation after stent implantation, balloon angioplasty, or endarterectomy. Since the mouse presents many advantages and is the most frequently used model for studying molecular processes, the current study proposes an invasive procedure of endothelial denudation, also known as the wire-injury model, which is representative of the human condition of neointima formation in arteries after revascularization procedures.

This study describes an invasive procedure for the induction of accelerated atherosclerosis in mice. In comparison to other methods using electric- or cryo-induced injury, mechanical-induced injury mimics the human condition of restenosis after revascularization therapies and is ideal for the study of the molecular mechanisms involved.

Inducción de la Aterosclerosis Acelerada en Ratones: El Modelo de "Lesiones por Alambre"

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. ...