Name: protocol for long duration whole body hyperthermia in mice
Uploaded: 2012-08-25T12:00:00.000+00:00
Duration: 7 min 56 s
Description: Watch this Scientific Journal Video about Protocol for Long Duration Whole Body Hyperthermia in Mice at JoVE.com

1. Ética Animal Antes de realizar la hipertermia larga duración en ratones asegurarse de que el procedimiento ha sido aprobado por el Cuidado de Animales institucional y el empleo. Todos los procedimientos descritos en este documento y se muestra en el video que lo acompaña fueron aprobados por el Comité Institucional de Ética Animal del Instituto Nacional de Inmunología. 2. Entendimiento hipertermia La hipertermia de todo el cuerpo (WBH) se administra mediante la colocación de los animales en jaulas precalentado que se colocan en una incubadora mantenida a 39,5 ° C. En la estandarización de protocolo, un sensor de temperatura que se implantan quirúrgicamente en los ratones y su temperatura corporal se controló en diferentes condiciones experimentales. Se observó que, al colocar los animales en ambiente caliente, su temperatura aumenta gradualmente desde 37 ° C a un máximo de 42 ° C durante la duración de 100 min (Figura 1). The resultante &quot;pico&quot; de la temperatura es intrigante que la temperatura interna del cuerpo disparo incluso superior a la temperatura ambiental externa. Cuando la temperatura corporal superior a 40 ° C, el animal muestra signos de estrés y la deshidratación, tales como agentes humectantes alrededor del hocico. Aumento de la temperatura corporal superior a 40 º C, dará lugar a la humedad y el estrés irreversible e incluso la muerte de los animales debido al estrés térmico. Por lo tanto, es importante para prevenir los picos de temperatura durante el curso de la hipertermia. Este fenómeno de los picos de alta temperatura está asociado con la hiperactividad física de los animales durante la exposición hipertermia. Picos de temperatura similares fueron observados por otros grupos y también estaban asociados con la hiperactividad física del animal al ser introducido en el medio ambiente con temperaturas más altas 10. En el protocolo, los ratones se inmovilizan durante la exposición hipertermia. Comose muestra en la Figura 2, la inmovilización de los animales evita los picos de temperatura. Hemos utilizado 8-12 semanas de edad BALB / cJ ratones para demostrar este protocolo. El protocolo no está restringida a un tipo particular / deformación de los ratones. 3. Preparación para el Experimento 3,1 Incubadora Este experimento se puede realizar en una incubadora de CO 2 normales, ya que tienen un buen control de temperatura. Desconecte el suministro de gas CO 2 y retire la bandeja de retención de agua de la incubadora de CO 2. En algunos modelos de incubadoras es posible desactivar el controlador de CO 2. Organizar estantes de la incubadora para que una jaula ratones podrían ser colocados convenientemente dentro. Establecer la temperatura de la incubadora a 39,5 ° C. 3,2 Jaulas Típicamente, la hipertermia experimento se realiza en 4 ratones a la vez. Dos jaulas se requieren; ene se coloca dentro de la incubadora, y el otro se coloca fuera a temperatura ambiente. Ropa de cama de las jaulas se evita, como las manchas de ropa de cama que se humedezca con el tiempo que da lugar a una aplicación no uniforme de temperatura dentro de la jaula. La caja exterior debe tener bolitas de comida y una botella de agua. 3,3 Ratones tubos de inmovilización Durante el curso de la primera 4 ciclos de ratones hipertermia son inmovilizados en tubos perforados. Estos tubos de inmovilización puede estar hecha de tubos de 50 &#39;de centrífuga&#39; ml por agujeros de la perforación 3 mm en todo su cuerpo y cuatro de tales tubos se requiere. El tubo de 50 ml convenientemente se puede inmovilizar BALB / cJ ratones que tienen más de 8 semanas. Tubos de tamaños apropiados pueden ser necesarios para algunas cepa inusualmente diferente de ratones o de los ratones que son muy jóvenes o mayores de 50 semanas. Colocar los tubos de inmovilización y una jaula dentro de la incubadora mantenida a 39,5 ° C. Espere por lo menos 2 horas para que la jaula y metubos mmobilization alcanzar la temperatura de la incubadora. 4. Primer ciclo de la hipertermia Los ratones pueden sufrir deshidratación durante la exposición hipertermia. Por lo tanto, antes de comenzar el experimento, se administran 0,5 ml de solución salina normal por vía intraperitoneal a cada ratón. Use una aguja de 26 G con jeringa de 1 ml. Quítese rápidamente la jaula colocada en la incubadora, coloque un animal en cada uno de los tubos de inmovilización y coloque la jaula en la incubadora. Registre el tiempo. Es esencial mantener la jaula en el mismo lugar en la incubadora cada vez. Después de 90 minutos, sacar la jaula de la incubadora. Liberar los animales de los tubos de inmovilización y colocarlos en la jaula a temperatura normal con un fácil acceso a comida y agua. Colocar los tubos vacíos de inmovilización de nuevo en la incubadora. Después de 15 min, el segundo ciclo de la hipertermia se inicia mediante la entrega de 0.5 ml de solución salina por vía intraperitoneal a cada ratón. Luego se inmoviliza en tubos de 50 ml de inmovilización perforadas y colocadas en la incubadora. 5. Los ciclos posteriores hipertermia Por primera 4 ciclos, es esencial para inmovilizar los ratones durante la exposición, la hipertermia y para los dos primeros ciclos, inyección de solución salina se administra antes de comenzar el período de hipertermia. Después de estos ciclos de hipertermia seguido de un descanso se completan, los ratones conseguir aclimatarse y no vuelven hiperactivos durante la exposición hipertermia. La inyección intraperitoneal de solución salina puede no ser necesario si los ratones fácilmente tomar alimentos y agua durante el tiempo de reposo. 6. Después de todos los ciclos completados, el último paso consiste en examinar a los animales No debería haber ninguna muerte durante los ciclos de hipertermia. Cada animal tiene que ser vigilado muy cuidadosamente en el primercuantos ciclos. Rápidamente buscar cualquier humectante alrededor del hocico. Este síntoma es una firma de deshidratación. Los ratones con síntomas tales inmediatamente se debe dar 0,5 ml de solución salina normal ip y el resto a temperatura ambiente. La mayoría de los ratones inmovilizados no se requiere ninguna atención adicional y con éxito soportar los esfuerzos de la hipertermia. Después de completar los ciclos requeridos, los animales pueden parecer débil y deshidratado, pero rápidamente se recuperan en pocas horas. <img src="/files/ftp_upload/3801/3801fig1.jpg" alt="Figura 1" /> Figura 1. Variación de la temperatura corporal de los ratones cuando la jaula se colocó en una incubadora a 39,5 ° C. Después de 90 min la jaula se retiró de la incubadora y se colocaron a 25 º C. Los círculos rojos indican los picos de alta temperatura. <img src="/files/ftp_upload/3801/3801fig2.jpg" alt="Figura 2" /> Figura 2. Variación de la temperatu cuerpo de núcleore de una Ratones inmovilizados durante los ciclos de hipertermia. Después de inmovilizar el animal, los picos de las altas temperaturas no se observa cuando la jaula se colocó a 39,5 ° C.

<ol>
	<li>Braude, A. I., Beck, J., Zalesky, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Febrile+response+to+bacterial+pyrogens+in+leukemia.">Febrile response to bacterial pyrogens in leukemia.</a> Blood. 16, 1279 (1960).</li><li>Dovern, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperthermic+intraperitoneal+chemotherapy+added+to+the+treatment+of+ovarian+cancer.+A+review+of+achieved+results+and+complications.">Hyperthermic intraperitoneal chemotherapy added to the treatment of ovarian cancer. A review of achieved results and complications.</a> Eur. J. Gynaecol. Oncol. 31, 256 (2010).</li><li>Gaworek, J., Mayer, C. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systemic+whole+body+hyperthermia+in+oncology:+fatal+heat+for+tumor+cells.">Systemic whole body hyperthermia in oncology: fatal heat for tumor cells.</a> Pflege. Z. 56, 15 (2003).</li><li>Hegewisch-Becker, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+whole+body+hyperthermia+(41.8+degrees+C)+on+the+frequency+of+tumor+cells+in+the+peripheral+blood+of+patients+with+advanced+malignancies.">Effects of whole body hyperthermia (41.8 degrees C) on the frequency of tumor cells in the peripheral blood of patients with advanced malignancies.</a> Clin. Cancer Res. 9, 2079 ( ).</li><li>Jia, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhibition+of+B16+murine+melanoma+metastasis+and+enhancement+of+immunity+by+fever-range+whole+body+hyperthermia.">Inhibition of B16 murine melanoma metastasis and enhancement of immunity by fever-range whole body hyperthermia.</a> Int. J. Hyperthermia. 27, 275 (2011).</li><li>Maluta, S., Dall'oglio, S., Nadalini, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment+for+intermediate+and+high-risk+prostate+cancer:+controversial+issues+and+the+role+of+hyperthermia.">Treatment for intermediate and high-risk prostate cancer: controversial issues and the role of hyperthermia.</a> Int. J. Hyperthermia. 26, 765 (2010).</li><li>Moyer, H. R., Delman, K. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+hyperthermia+in+optimizing+tumor+response+to+regional+therapy.">The role of hyperthermia in optimizing tumor response to regional therapy.</a> Int. J. Hyperthermia. 24, 251 (2008).</li><li>Muthana, M., Multhoff, G., Pockley, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tumour+infiltrating+host+cells+and+their+significance+for+hyperthermia.">Tumour infiltrating host cells and their significance for hyperthermia.</a> Int. J. Hyperthermia. 26, 247 (2010).</li><li>Ostberg, J. R., Repasky, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+the+effects+of+two+different+whole+body+hyperthermia+protocols+on+the+distribution+of+murine+leukocyte+populations.">Comparison of the effects of two different whole body hyperthermia protocols on the distribution of murine leukocyte populations.</a> Int. J. Hyperthermia. 16, 29 (2000).</li><li>Pritchard, M. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Protocols+for+simulating+the+thermal+component+of+fever:+preclinical+and+clinical+experience.">Protocols for simulating the thermal component of fever: preclinical and clinical experience.</a> Methods. 32, 54 (2004).</li><li>Repasky, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+mild+whole-body+hyperthermia+protocols+using+human+breast,+ovarian,+and+colon+tumors+grown+in+severe+combined+immunodeficient+mice.">Characterization of mild whole-body hyperthermia protocols using human breast, ovarian, and colon tumors grown in severe combined immunodeficient mice.</a> Infect. Dis. Obstet. Gynecol. 7, 19 (1999).</li><li>Willnow, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment+of+otherwise+incurable+tumor+diseases+in+childhood+using+whole-body+hyperthermia+and+chemotherapy.">Treatment of otherwise incurable tumor diseases in childhood using whole-body hyperthermia and chemotherapy.</a> Dtsch. Med. Wochenschr. 114, 208 (1989).</li></ol>

No tenemos nada que revelar.

<html> Ya en el 5.000 aC, los médicos egipcios tumores tratados con calor. Los griegos reconocido el valor de calor en algunos tratamientos médicos. Los textos más antiguos de la Ley de Moisés mención de aguas termales (Génesis 36:24) para elevar la temperatura del cuerpo terapéuticamente. Las técnicas anteriores emplean ya sea el uso de extractos microbianos pirogénicas para la inducción de fiebre o baños de agua caliente para la inducción de hipertermia 1. Sin embargo...

<table border="1"><tr><td></td><td></td><td></td><td></td></tr><tr><td> Termistor </td><td> Amidata </td><td> 528-8558 </td><td></td></tr><tr><td> CO 2 incubadora </td><td> Heraeus </td><td> B5060 EK-CO2 </td><td></td></tr><tr><td> Ratones jaulas </td><td> Citizen INDUSTRIES LTD. </td><td></td><td> Tipo B 365X207X190 cm </td></tr><tr><td> Alimentos para animales </td><td> Provimi India </td><td></td><td></td></tr><tr><td> Botella de agua para jaula </td><td> Proveedor local </td><td></td><td> Botella de cristal </td></tr><tr><td> Soldador </td><td> Solderon, India </td><td></td><td></td></tr><tr><td> 50 ml tubos de centrífuga </td><td> BD Biosciences </td><td> 352070 </td><td></td></tr><tr><td> Timer </td><td> Proveedor local </td><td></td><td></td></tr><tr><td> 1 ml jeringa con aguja 26G </td><td> BD Biosciences </td><td> 309602 </td><td></td></tr><tr><td> Salina </td><td> Proveedor local </td><td></td><td></td></tr></table>

protocol for long duration whole body hyperthermia in mice

La hipertermia es un término general utilizado para definir el aumento de la temperatura corporal por encima de lo normal. A menudo se utiliza para describir el aumento de la temperatura corporal central que se observa durante la fiebre. El uso de la hipertermia como un adyuvante se ha convertido en un procedimiento prometedor para la regresión del tumor en el campo de la biología del cáncer. Para este propósito, el requisito más importante es tener protocolos de calentamiento seguro y uniforme. Hemos desarrollado un protocolo para la hipertermia (cuerpo entero) en ratones. En este protocolo, los animales son expuestos a ciclos de hipertermia durante 90 minutos seguido de un período de descanso de 15 min. Durante este periodo los ratones tienen fácil acceso a comida y agua. Altos picos de temperatura corporal en los ratones durante la primera exposición de algunos ciclos de hipertermia se impide mediante la inmovilización del animal. Además, solución salina normal se administra en ciclos primero para reducir al mínimo los efectos de la deshidratación. Este protocolo se puede simular condiciones similares a la fiebre en los ratones hasta 12-24 horas. Tenemosutilizado 8-12 semanas de edad BALB / cJ ratones hembra para demostrar el protocolo.

Watch this Scientific Journal Video about Protocol for Long Duration Whole Body Hyperthermia in Mice at JoVE.com

Protocol for Long Duration Whole Body Hyperthermia in Mice

En este trabajo se describe un protocolo para la hipertermia de todo el cuerpo en ratones que pueden estimular la fiebre como condiciones hasta 12-24 horas.

Protocolo para la hipertermia corporal Larga Duración Total en ratones

Hyperthermia is a general term used to define the increase in core body temperature above normal. It is often used to describe the increased core body ...

protocol-for-long-duration-whole-body-hyperthermia-in-mice

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

11.5K vistas.  National Institute of Immunology. En este trabajo se describe un protocolo para la hipertermia de todo el cuerpo en ratones que pueden estimular la fiebre como condiciones hasta 12-24 horas.

Video: Protocol for Long Duration Whole Body Hyperthermia in Mice

Magnetic Resonance-Guided High Intensity Focused Ultrasound Generated Hyperthermia: A Feasible Treatment Method in a Murine Rhabdomyosarcoma Model

Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is an established method for producing localized hyperthermia. Given the real-time imaging and acoustic energy modulation, this modality enables precise temperature control within a defined area. Many thermal applications are being explored with this noninvasive, nonionizing technology, such as hyperthermia generation, to release drugs from thermosensitive liposomal carriers. These drugs can include chemotherapies such as doxorubicin, for which targeted release is desired due to the dose-limiting systemic side effects, namely cardiotoxicity. Doxorubicin is a mainstay for treating a variety of malignant tumors and is commonly used in relapsed or recurrent rhabdomyosarcoma (RMS). RMS is the most common solid soft tissue extracranial tumor in children and young adults. Despite aggressive, multimodal therapy, RMS survival rates have remained the same for the past 30 years. To explore a solution for addressing this unmet need, an experimental protocol was developed to evaluate the release of thermosensitive liposomal doxorubicin (TLD) in an immunocompetent, syngeneic RMS mouse model using MRgHIFU as the source of hyperthermia for drug release.

Presented here is a protocol to use controlled hyperthermia, generated by magnetic resonance-guided high intensity focused ultrasound, to trigger drug release from temperature-sensitive liposomes in a rhabdomyosarcoma mouse model.

Hipertermia generada por ultrasonido focalizado de alta intensidad guiada por resonancia magnética: un método de tratamiento factible en un modelo de rabdomiosarcoma murino

Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is an established method for producing localized hyperthermia. Given the real-time ...

Investigación

Investigación sobre el cáncer

Measuring Skeletal Muscle Thermogenesis in Mice and Rats

Skeletal muscle thermogenesis provides a potential avenue for better understanding metabolic homeostasis and the mechanisms underlying energy expenditure. Surprisingly little evidence is available to link the neural, myocellular, and molecular mechanisms of thermogenesis directly to measurable changes in muscle temperature. This paper describes a method in which temperature transponders are utilized to retrieve direct measurements of mouse and rat skeletal muscle temperature.
Remote transponders are surgically implanted within the muscle of mice and rats, and the animals are given time to recover. Mice and rats must then be repeatedly habituated to the testing environment and procedure. Changes in muscle temperature are measured in response to pharmacological or contextual stimuli in the home cage. Muscle temperature can also be measured during prescribed physical activity (i.e., treadmill walking at a constant speed) to factor out changes in activity as contributors to the changes in muscle temperature induced by these stimuli.
This method has been successfully used to elucidate mechanisms underlying muscle thermogenic control at the level of the brain, sympathetic nervous system, and skeletal muscle. Provided are demonstrations of this success using predator odor (PO; ferret odor) as a contextual stimulus and injections of oxytocin (Oxt) as a pharmacological stimulus, where predator odor induces muscle thermogenesis, and Oxt suppresses muscle temperature. Thus, these datasets display the efficacy of this method in detecting rapid changes in muscle temperature.

Mice and rats are surgically implanted with remote temperature transponders and then habituated to the testing environment and procedure. Changes in muscle temperature are measured in response to pharmacological or contextual stimuli in the home cage or during prescribed physical activity (i.e., treadmill walking at a constant speed).

Medición de la termogénesis del músculo esquelético en ratones y ratas

Skeletal muscle thermogenesis provides a potential avenue for better understanding metabolic homeostasis and the mechanisms underlying energy expenditure. ...

Comportamiento

Explorando el intercambio de metabolitos en el tejido adiposo marrón

Arteriovenous Metabolomics to Measure In Vivo Metabolite Exchange in Brown Adipose Tissue

Brown adipose tissue (BAT) plays a crucial role in regulating metabolic homeostasis through a unique energy expenditure process known as non-shivering thermogenesis. To achieve this, BAT utilizes a diverse menu of circulating nutrients to support its high metabolic demand. Additionally, BAT secretes metabolite-derived bioactive factors that can serve as either metabolic fuels or signaling molecules, facilitating BAT-mediated intratissue and/or intertissue communication. This suggests that BAT actively participates in systemic metabolite exchange, an interesting feature that is beginning to be explored. Here, we introduce a protocol for in vivo mouse-level optimized BAT arteriovenous metabolomics. The protocol focuses on relevant methods for thermogenic stimulations and an arteriovenous blood sampling technique using Sulzer's vein, which selectively drains interscapular BAT-derived venous blood and systemic arterial blood. Next, a gas chromatography-based metabolomics protocol using those blood samples is demonstrated. The use of this technique should expand the understanding of BAT-regulated metabolite exchange at the inter-organ level by measuring the net uptake and release of metabolites by BAT.

Autor destacado: Iluminando nuevas vías para el metabolismo del tejido adiposo y la prevención de enfermedades 

In this protocol, methods relevant for BAT-optimized arteriovenous metabolomics using GC-MS in a mouse model are outlined. These methods allow for the acquisition of valuable insights into BAT-mediated metabolite exchange at the organismal level.

Metabolómica arteriovenosa para medir el intercambio de metabolitos in vivo en tejido adiposo marrón

Brown adipose tissue (BAT) plays a crucial role in regulating metabolic homeostasis through a unique energy expenditure process known as non-shivering ...

Bioquímica

Mouse Body Temperature Measurement Using Infrared Thermometer During Passive Systemic Anaphylaxis and Food Allergy Evaluation

Mouse body temperature measurement is of paramount importance for investigating allergies and anaphylactic symptoms. Rectal probes for temperature readings is common, and they have been proven to be accurate and invaluable in this regard. However, this method of temperature measurement requires the mice to be anesthetized in order to insert the probe without injury to the animal. This limits the ability to observe other phenotypes of the mouse simultaneously. In order to investigate other phenotypes while measuring temperatures, rectal probes are not ideal, and another method is desired. Here, we introduce a noninvasive method of temperature measurement that foregoes the requirement for mouse anesthesia while maintaining equal reliability to rectal probes in measuring body temperature. We use an infrared thermometer that detects body surface temperatures at ranges between 2 and 150 mm. This method of body temperature measurement is successful in reliably replicating temperature change trends during passive system anaphylaxis experiments in mice. We show that body surface temperatures are about 2.0 &#176;C lower than rectal probe measurements, but the degree of temperature drop follows the same trend. Furthermore, we use the same technique to observe mice in a food allergy model to evaluate temperature and activity levels simultaneously.

Here we present a new method to accurately measure body temperature differences in passive systemic anaphylaxis (PSA) and food allergy mouse models using an infrared thermometer. This procedure has been accurately duplicated in previous PSA results.

Medición de la temperatura del cuerpo de ratón con termómetro infrarrojo pasiva Anafilaxia sistémica y evaluación de la alergia alimentaria

Mouse body temperature measurement is of paramount importance for investigating allergies and anaphylactic symptoms. Rectal probes for temperature ...

Inmunología e Infección

Magnetic-, Acoustic-, and Optical-Triple-Responsive Microbubbles for Magnetic Hyperthermia and Pothotothermal Combination Cancer Therapy

The precision delivery of anti-cancer agents which aim for targeted and deep-penetrated delivery as well as a controlled release at the tumor site has been challenged. Here, we fabricate iron oxide nanoparticle shelled microbubbles (NSMs) through self-assembly, synergizing magnetic, acoustic, and optical responsiveness in one nanotherapeutic platform. Iron oxide nanoparticles serve as both magnetic and photothermal agents. Once intravenously injected, NSMs can be magnetically guided to the tumor site. Ultrasound triggers the release of iron oxide nanoparticles, facilitating the penetration of nanoparticles deep into the tumor due to the cavitation effect of microbubbles. Thereafter, magnetic hyperthermia and photothermal therapy can be performed on the tumor for combinational cancer therapy, a solution for cancer resistance due to the tumor heterogeneity. In this protocol, the synthesis and characterization of NSMs including structural, chemical, magnetic and acoustic properties were performed. In addition, the anti-cancer efficacy by thermal therapy was investigated using in vitro cell cultures. The proposed delivery strategy and combination therapy holds great promise in cancer treatment to improve both delivery and anticancer efficacies.

Presented here is a protocol for the fabrication of iron oxide nanoparticle-shelled microbubbles (NSMs) through self-assembly, synergizing magnetic, acoustic, and optical responsiveness in one nanotherapeutic platform for magnetic hyperthermia and photothermal combination cancer therapy.

Microburbujas magnéticas, acústicas y ópticas de triple respuesta para la hipertermia magnética y la terapia combinada de cáncer potototérmico

The precision delivery of anti-cancer agents which aim for targeted and deep-penetrated delivery as well as a controlled release at the tumor site has ...

Bioingeniería

A Behavioral Screen for Heat-Induced Seizures in Mouse Models of Epilepsy

Transgenic mouse models have proved to be powerful tools in studying various aspects of human neurological disorders, including epilepsy. The SCN1A-associated genetic epilepsies comprise a wide spectrum of seizure disorders with incomplete penetrance and clinical variability. SCN1A mutations can result in a large variety of seizure phenotype ranging from simple, self-limited fever-associated febrile seizures (FS), moderate-level genetic epilepsy with febrile seizures plus (GEFS+) to more severe Dravet Syndrome (DS). Although FS are commonly seen in children below 6-7 years of age who do not have genetic epilepsy, FS in GEFS+ patients continue to occur into adulthood. Traditionally, experimental FS have been induced in mice by exposing the animal to a stream of dry air or heating lamps, and the rate of change in body temperature is often not well controlled. Here, we describe a custom-built heating chamber, with a plexiglass front, that is fitted with a digital temperature controller and a heater-equipped electric fan, which can send heated forced air into the test arena in a temperature-controlled manner. The body temperature of a mouse placed in the chamber, monitored through a rectal probe, can be increased to 40-42 &#176;C in a reproducible manner by increasing the temperature inside the chamber. Continual visual monitoring of the animals during the heating period demonstrates induction of heat-induced seizures in mice carrying an FS mutation at a body temperature that does not elicit behavioral seizures in wild-type litter mates. Animals can be easily removed from the chamber and placed on a cooling pad to rapidly return body temperature to normal. This method provides for a simple, rapid, and reproducible screening protocol for the occurrence of heat-induced seizures in epilepsy mouse models.

The goal of the method is to screen for hyperthermia or heat-induced seizures in mouse models. The protocol describes the use of a custom-built chamber with continuous monitoring of the body temperature to determine whether elevated body temperature leads to seizures.

Una prueba conductual para las convulsiones inducidas por el calor en modelos de epilepsia en ratones

Transgenic mouse models have proved to be powerful tools in studying various aspects of human neurological disorders, including epilepsy. The ...

Neurociencias

Short-Duration Hypothermia Induction in Rats using Models for Studies examining Clinical Relevance and Mechanisms

Therapeutic hypothermia (TH) is a powerful neuroprotective strategy that has provided robust evidence for neuroprotection in pre-clinical studies of neurological disorders. Despite strong pre-clinical evidence, TH has not shown efficacy in clinical trials of most neurological disorders. The only successful trials employing therapeutic hypothermia were related to cardiac arrest in adults and hypoxic ischemic injury in neonates. Further investigations into the parameters of its use, and study design comparisons between pre-clinical and clinical studies, are warranted. This article demonstrates two methods of short-duration hypothermia induction. The first method allows for rapid hypothermia induction in rats using ethanol spray and fans. This method works by cooling the skin, which has been less commonly used in clinical trials and may have different physiological effects. Cooling is much more rapid with this technique than is achievable in human patients due to differences in surface area to volume ratio. Along with this, a second method is also presented, which allows for a clinically achievable cooling rate for short-duration hypothermia. This method is easy to implement, reproducible and does not require active skin cooling.

This article describes two methods of whole-body short-duration hypothermia induction in rats. The first, rapid induction method, employs active cooling using fans and ethanol spray for a rapid decrease in temperature. The second method is a gradual cooling method. This is achieved using the combination of isoflurane anesthesia and the reduction of temperature settings on the homeothermic heat mat. This results in a gradual decrease in core body temperature without the use of any external cooling devices.&#160;

Inducción de hipotermia de corta duración en ratas utilizando modelos para estudios que examinan la relevancia clínica y los mecanismos

Therapeutic hypothermia (TH) is a powerful neuroprotective strategy that has provided robust evidence for neuroprotection in pre-clinical studies of ...

Medicina

A Preclinical Model of Exertional Heat Stroke in Mice

Heat stroke is the most severe manifestation of heat-related illnesses. Classic heat stroke (CHS), also known as passive heat stroke, occurs at rest, whereas exertional heat stroke (EHS) occurs during physical activity. EHS differs from CHS in etiology, clinical presentation, and sequelae of multi-organ dysfunction. Until recently, only models of CHS have been well established. This protocol aims to provide guidelines for a refined preclinical mouse model of EHS that is free from major limiting factors such as the use of anesthesia, restraint, rectal probes, or electric shock. Male and female C57Bl/6 mice, instrumented with core temperature (Tc) telemetric probes were utilized in this model. For familiarization with the running mode, mice undergo 3 weeks of training using both voluntary and forced running wheels. Thereafter, mice run on a forced wheel inside a climatic chamber set at 37.5 &#176;C and 40%-50% relative humidity (RH) until displaying symptom limitation (e.g., loss of consciousness) at Tc of 42.1-42.5 &#176;C, although suitable results can be obtained at chamber temperatures between 34.5-39.5 &#176;C and humidity between 30%-90%. Depending on the desired severity, mice are removed from the chamber immediately for recovery in ambient temperature or remain in the heated chamber for a longer duration, inducing a more severe exposure and a higher incidence of mortality. Results are compared with sham-matched exercise controls (EXC) and/or na&#239;ve controls (NC). The model mirrors many of the pathophysiological outcomes observed in human EHS, including loss of consciousness, severe hyperthermia, multi-organ damage as well as inflammatory cytokine release, and acute phase responses of the immune system. This model is ideal for hypothesis-driven research to test preventative and therapeutic strategies that may delay the onset of EHS or reduce the multi-organ damage that characterizes this manifestation.

The protocol describes the development of a standardized, repeatable, preclinical model of exertional heat stroke (EHS) in mice free from adverse external stimuli such as electric shock. The model provides a platform for mechanistic, preventative, and therapeutic studies.

Un modelo preclínico de golpe de calor por esfuerzo en ratones

Heat stroke is the most severe manifestation of heat-related illnesses. Classic heat stroke (CHS), also known as passive heat stroke, occurs at rest, ...

Protocolo para la hipertermia corporal Larga Duración Total en ratones

Resumen

Explorar más videos

Capítulos en este video

Hipertermia generada por ultrasonido focalizado de alta intensidad guiada por resonancia magnética: un método de tratamiento factible en un modelo de rabdomiosarcoma murino

Medición de la termogénesis del músculo esquelético en ratones y ratas

Metabolómica arteriovenosa para medir el intercambio de metabolitos in vivo en tejido adiposo marrón

Metabolómica arteriovenosa para medir el intercambio de metabolitos in vivo en tejido adiposo marrón

Metabolómica arteriovenosa para medir el intercambio de metabolitos in vivo en tejido adiposo marrón

Medición de la temperatura del cuerpo de ratón con termómetro infrarrojo pasiva Anafilaxia sistémica y evaluación de la alergia alimentaria

Microburbujas magnéticas, acústicas y ópticas de triple respuesta para la hipertermia magnética y la terapia combinada de cáncer potototérmico

Una prueba conductual para las convulsiones inducidas por el calor en modelos de epilepsia en ratones

Inducción de hipotermia de corta duración en ratas utilizando modelos para estudios que examinan la relevancia clínica y los mecanismos

Un modelo preclínico de golpe de calor por esfuerzo en ratones