1. Animal Ethics Prima di eseguire l&#39;ipertermia lunga durata sui topi fare in modo che la procedura sia stata approvata dalla cura degli animali e del Comitato Istituzionale uso. Tutte le procedure descritte in questo documento e mostrato nel video allegato è stato approvato dal Comitato Etico Istituzionale Animale dell&#39;Istituto Nazionale di Immunologia. 2. Comprendere Ipertermia L&#39;ipertermia Whole Body (WBH) viene fornito mettendo gli animali in gabbia preriscaldata che vengono inseriti nella incubatore mantenuto a 39,5 ° C. Durante la standardizzazione del protocollo, un sensore di temperatura è stato impiantato chirurgicamente nei topi e la loro temperatura corporea è stata monitorata in diverse condizioni sperimentali. È stato osservato che contestualmente all&#39;invio degli animali in ambiente riscaldato, la temperatura gradualmente aumentata da 37 ° C fino a 42 ° C per la durata di 100 min (Figura 1). The conseguente &quot;spike&quot; in temperatura è interessante in quanto la temperatura corporea interna girato addirittura superiore alla temperatura dell&#39;ambiente esterno. Quando la temperatura corporea supera i 40 ° C, l&#39;animale mostra segni di stress e disidratazione come bagnare intorno al muso. Aumentare la temperatura corporea di 40 ° C, porterà alla bagnatura e stress irreversibili o addirittura la morte degli animali a causa di stress da calore. Quindi è importante prevenire i picchi di temperatura durante il corso di ipertermia. Questo fenomeno di picchi di alta temperatura è associato con l&#39;iperattività fisica di animali durante l&#39;esposizione ipertermia. Picchi di temperatura simili sono stati osservati anche da altri gruppi e sono stati associati con l&#39;iperattività fisica dell&#39;animale dopo essere stato introdotto ambiente con temperature superiori 10. Nel nostro protocollo, i topi sono immobilizzati durante l&#39;esposizione ipertermia. Comeillustrato nella figura 2, immobilizzazione animale evita i picchi di temperatura. Abbiamo usato 8-12 settimane vecchi BALB / Cj topi per dimostrare questo protocollo. Il protocollo non è limitata ad un particolare tipo / ceppo dei topi. 3. Preparazione per l&#39;esperimento 3,1 Incubatore Questo esperimento può essere eseguita in un normale CO 2 incubatore in quanto hanno un buon controllo della temperatura. Scollegare CO 2 gas e rimuovere il vassoio di ritenzione idrica del CO 2 incubatore. In alcuni modelli di incubatori è possibile spegnere il CO 2 controller. Disporre ripiani dell&#39;incubatore in modo che una gabbia topi potrebbe essere convenientemente posizionati all&#39;interno. Impostare la temperatura del termostato a 39,5 ° C. 3,2 Gabbie Tipicamente, l&#39;esperimento ipertermia viene eseguita su topi 4 alla volta. Due gabbie sono necessarie; sule viene collocato all&#39;interno dell&#39;incubatrice e l&#39;altro è posto fuori a temperatura ambiente. Biancheria di gabbie è evitato, come le macchie di biancheria si bagnano con il tempo che si traduce in non uniforme della temperatura all&#39;interno della gabbia. La gabbia esterna dovrebbe avere pellet alimentari e bottiglia d&#39;acqua. 3,3 Mouse immobilizzazione tubi Nel corso del primi 4 cicli di ipertermia topi sono immobilizzati in tubi forati. Questi tubi di immobilizzazione può essere fatto da 50 provette &#39;centrifuga&#39; ml di perforazione 3 mm fori su tutto il corpo e quattro di tali tubi sarà richiesto. Il tubo 50ml può comodamente immobilizzare BALB / Cj topi di età superiore a 8 settimane. Tubi di dimensioni adeguate può essere richiesto per un po &#39;di sforzo insolitamente diversi di topi o per i topi che sono molto giovani o di età superiore a 50 settimane. Tubi immobilizzazione posto e una gabbia all&#39;interno della incubatore mantenuto a 39,5 ° C. Attendere almeno due ore in modo che la gabbia e hotubi mmobilization raggiungere la temperatura dell&#39;incubatore. 4. Primo ciclo di ipertermia I topi possono andare incontro a disidratazione durante l&#39;esposizione ipertermia. Quindi prima di iniziare l&#39;esperimento, amministrare 0,5 ml soluzione fisiologica per via intraperitoneale ad ogni mouse. Utilizzare un ago 26 G con siringa da 1 ml. Rapidamente smontare la gabbia posta in incubatrice, posto un animale in ogni tubi immobilizzazione e posizionare la gabbia in incubatrice. Registrare il tempo. E &#39;essenziale per mantenere la gabbia nello stesso luogo in incubatrice ogni volta. Dopo 90 minuti, togliere la gabbia dal termostato. Rilasciare gli animali dai tubi di immobilizzazione e metterli in gabbia a temperatura normale, con facile accesso al cibo e all&#39;acqua. Inserire le provette immobilizzazione vuoti di nuovo in incubatrice. Dopo 15 min, il secondo ciclo di ipertermia viene avviato fornendo 0.5 ml di soluzione fisiologica per via intraperitoneale ad ogni topo. Essi vengono poi immobilizzate in provette da 50 ml immobilizzazione forati e posto nell&#39;incubatrice. 5. Cicli Ipertermia successivi Per primi 4 cicli, è essenziale immobilizzare topi durante l&#39;esposizione ipertermia e per i primi due cicli, iniezione di soluzione salina è data prima dell&#39;inizio del periodo di ipertermia. Dopo questi cicli di ipertermia seguiti da altri sono stati completati, i topi ottenere acclimatarsi e non diventare iperattivi durante l&#39;esposizione ipertermia. L&#39;iniezione intraperitoneale di soluzione salina può non essere necessario se i topi facilmente portare cibo e acqua durante il tempo di riposo. 6. Dopo aver completato tutti i cicli, il passo finale è quello di esaminare gli Animali Non ci dovrebbe essere alcuna morte durante i cicli di ipertermia. Ogni animale deve essere attentamente osservato il primopochi cicli. Rapidamente cercare qualsiasi bagnante intorno al muso. Questo sintomo è una firma di disidratazione. I topi con questi sintomi deve essere immediatamente data ip 0,5 ml soluzione fisiologica e di riposo a temperatura ambiente. La maggior parte dei topi immobilizzati non richiedono alcuna cura supplementare, e con successo sopportare lo stress della ipertermia. Dopo aver completato i cicli richiesti, gli animali possono apparire debole e disidratato, ma saranno presto recuperare entro poche ore. <img src="/files/ftp_upload/3801/3801fig1.jpg" alt="Figura 1" /> Figura 1. Variazione della temperatura corporea dei topi quando la gabbia è stata posta in un incubatore a 39,5 ° C. Dopo 90 min la gabbia è stato rimosso dal termostato e posto a 25 ° C. Cerchi rossi indicano picchi di alta temperatura. <img src="/files/ftp_upload/3801/3801fig2.jpg" alt="Figura 2" /> Figura 2. Variazione della tempe corpo di mandrinore di un topi immobilizzati durante i cicli di ipertermia. Dopo immobilizzare l&#39;animale, alte temperature picchi non osservare quando la gabbia è stata posta a 39,5 ° C.

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	<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. 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<html> Già nel 5000 aC, i medici egiziani tumori trattati con il calore. I Greci riconosciuto il valore di calore in alcuni trattamenti medici. I testi più antichi della Legge di Mosè menzione sorgenti termali (Genesi 36:24), per elevare la temperatura corporea terapeuticamente. Le tecniche precedenti impiegato sia l&#39;uso di estratti microbici pirogene per l&#39;induzione della febbre o bagni di acqua calda per l&#39;induzione di ipertermia 1. Tuttavia nessuno di questi appro...

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protocol for long duration whole body hyperthermia in mice

Ipertermia è un termine generico usato per definire l&#39;aumento della temperatura corporea superiore al normale. E &#39;spesso usato per descrivere l&#39;aumento della temperatura corporea che si osserva durante la febbre. L&#39;uso di ipertermia come adiuvante è emerso come una procedura promettente per regressione del tumore nel campo della biologia del cancro. A questo scopo, il requisito più importante è avere protocolli riscaldamento affidabile e uniforme. Abbiamo sviluppato un protocollo per ipertermia (corpo) nei topi. In questo protocollo, gli animali sono esposti a cicli di ipertermia per 90 min seguito da un periodo di riposo di 15 min. Durante questo periodo i topi hanno facile accesso a cibo e acqua. Alti picchi di temperatura del corpo nei topi durante i cicli di ipertermia primi esposizione viene impedito immobilizzando l&#39;animale. Inoltre, soluzione salina viene somministrata prima pochi cicli per minimizzare gli effetti della disidratazione. Questo protocollo in grado di simulare condizioni di febbre come nei topi fino a 12-24 ore. Abbiamoutilizzato 8-12 settimane vecchi BALB / Cj topi femmina per dimostrare il protocollo.

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

Il presente documento descrive un protocollo per ipertermia tutto il corpo nei topi che possono stimolare la febbre come condizioni fino a 12-24 ore.

Protocollo per lungo Ipertermia Corpo intera durata in Mouse

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 Views.  National Institute of Immunology. Il presente documento descrive un protocollo per ipertermia tutto il corpo nei topi che possono stimolare la febbre come condizioni fino a 12-24 ore.

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.

Ipertermia generata da ultrasuoni focalizzati ad alta intensità guidata da risonanza magnetica: un metodo di trattamento fattibile in un modello di rabdomiosarcoma murino

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

Ricerca

Ricerca sul cancro

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).

Misurazione della termogenesi del muscolo scheletrico in topi e ratti

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

Comportamento

Esplorare lo scambio di metaboliti nel tessuto adiposo bruno

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.

Autore in primo piano: Illuminare nuove strade per il metabolismo del tessuto adiposo e la prevenzione delle malattie 

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.

Metabolomica arterovenosa per misurare lo scambio di metaboliti in vivo nel tessuto adiposo bruno

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

Biochimica

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.

Misurazione della temperatura corpo del mouse utilizzando il termometro a infrarossi durante passiva anafilassi sistemica e la valutazione di allergia alimentare

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

Immunologia e infezioni

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.

Microbolle magnetiche, acustiche e ottiche a tripla risposta per ipertermia magnetica e terapia del cancro combinata pototermica

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 ...

Bioingegneria

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.

Uno schermo comportamentale per le convulsioni indotte dal calore in modelli murini di epilessia

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

Neuroscienze

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;

Induzione dell'ipotermia di breve durata nei ratti utilizzando modelli per studi che esaminano la rilevanza clinica e i meccanismi

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.

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

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