Gli autori desiderano ringraziare Michele Allen del National Heart, Lung, and Blood Institute (NHLBI) dei National Institutes of Health (NIH) per la condivisione di generosamente la sua esperienza nei metodi di fenotipizzazione murine e per la sua assistenza tecnica in corso, così come per Timothy Hunt di NHLBI per aiutare a sviluppare il dispositivo di schermatura. Questo studio è sostenuto dalla Divisione di Intramural Research del National Institute of Nursing Research del NIH, e una parte del processo di validazione è supportata da una sovvenzione della Oncology Nursing Society Foundation.

Etica Dichiarazione: Questo studio è stato approvato dal National Institutes of Health (NIH) cura degli animali e del Comitato uso. Tutti i ricercatori che partecipano al trattamento degli animali e la misurazione dei risultati dello studio sono stati adeguatamente formati dall&#39;Ufficio NIH di cura degli animali e uso e il National Heart, Lung, and Blood Institute murino Fenotipizzazione core. Tutti gli aspetti della sperimentazione animale, gli alloggi, e le condizioni ambientali utilizzati in questo studio erano in conformità con la guida per la cura e l&#39;uso di animali da laboratorio 11. 1. L&#39;alloggio e animali da esperimento NOTA: Casa maschi C57BL / 6 topi (circa cinque settimane all&#39;arrivo) individualmente durante l&#39;esperimento e fornire ad libitum l&#39;accesso al cibo e all&#39;acqua. Tutte le gabbie sono tenuti al ciclo luce-buio 12:12 h con la fase di luce che inizia alle 6 del mattino e la fase di buio alle 6 del pomeriggio. <ol><li> Identificare i topi e assegnarli a singoli ventilare seriegabbie d mouse. Consentire 24 ore dopo la procedura di identificazione per il recupero. NOTA: il tatuaggio di coda è raccomandato come un mezzo di identificazione per eliminare la possibilità che un marchio auricolare potrebbe rimanere intrappolati in una ruota in esecuzione. Tatuaggio un numero sulla coda di ciascun topo, con il numero sulla coda corrispondente al numero scritto sulla gabbia del mouse. </li><li> Consentire topi si adatti alla loro gabbie per almeno tre giorni, manipolazione ogni mouse delicatamente per un periodo di tre minuti al giorno. </li></ol> 2. L&#39;esecuzione della rotella acclimatazione e Baseline <ol><li> Introdurre i topi alle singole gabbie VWRA, ciascuna dotata di una ruota in esecuzione collegato ad un contatore elettronico per la registrazione continua. NOTA: Tutti i contatori delle ruote connettersi a un computer tramite una sola interfaccia USB (vedere elenco dei materiali). Il software calcola il numero di giri delle ruote, la distanza percorsa e la velocità media di ciascun intervallo di tempo designato della duratio totale specificaton. Una volta che la registrazione si interrompe, i dati vengono automaticamente salvati sia come testo e fogli di calcolo. </li><li> Avviare la registrazione del VWRA attraverso l&#39;interfaccia software per computer. Impostare intervalli di registrazione a un&#39;ora e la durata di almeno cinque giorni. Continuare la registrazione VWRA per almeno cinque giorni. NOTA: Al termine della fase 2.2, tutti i topi dovrebbero raggiungere una quantità relativamente consistente di attività ruota gestione quotidiana. In caso contrario, quindi identificare ed escludere eventuali valori anomali. </li><li> Interrompere la registrazione VWRA tramite l&#39;interfaccia software, e restituire il mouse per loro gabbie standard descritti al punto 1.1 (gabbie senza correre ruote). </li><li> Randomize topi in nessuna delle due controllo sham-irradiati o gruppi irradiati. </li></ol> 3. L&#39;irradiazione Nota: eseguire i seguenti passaggi per tutti i mouse in entrambi i gruppi, una volta al giorno per tre giorni consecutivi. Trattare topi nello stesso ordine ogni giorno. <ol><li> Anestetizzare ogni topo mediante iniezione intraperitoneale diun ketamina (100 mg / kg) e xilazina (10 mg / kg) della miscela. </li><li> Confermare l&#39;anestesia con un pizzico punta e usare pomata sugli occhi per prevenire la secchezza mentre sotto anestesia. </li><li> Trasferire il mouse anestetizzato in un dispositivo di schermatura di piombo. Disporre il mouse nella schermatura in modo che solo la regione pelvica / addominale inferiore è esposta. NOTA: La schermatura è composta da due lead &quot;scatole&quot;, con uno spazio aperto stretto tra che permette l&#39;esposizione alle radiazioni ad una piccola regione di destinazione del mouse (vedi Figura 1). </li><li> Utilizzare nastro medico per fissare la base della coda del mouse nella posizione all&#39;interno della schermatura. NOTA: Passo 3.4 è facoltativo, ma in questo modo può contribuire a garantire che la posizione del mouse non cambia durante il passo successivo. </li><li> Trasportare il dispositivo di schermatura nel irradiatore, assicurando che la posizione degli animali all&#39;interno della schermatura viene mantenuta. </li><li> Se il mouse è nel gruppo irradiazione, consegnare 800 cGy a dose velocità di circa 110 cGy / min. Se il mouse è nel gruppo di controllo sham-irradiazione, lasciare il mouse nella irradiatore inattivo per il tempo equivalente. NOTA: le impostazioni ottimali irradiatore dipendono dal particolare dispositivo. Il rateo di dose di 110 cGy / min fornita da una fonte Cesio 137 è il rateo di dose centrale del irradiatore usato qui. Il tempo di esposizione è stata regolata a raggiungere la dose totale desiderata di 800 cGy. </li><li> Rimuovere il mouse dalla irradiatore e schermatura, e poi tornare alla sua gabbia originale, standard di cui al punto 1.1. </li><li> Monitorare costantemente il mouse fino a quando non ha ripreso conoscenza sufficiente a mantenere decubito sternale. </li></ol> 4. Misura fatica indotta da radiazioni <ol><li> Il giorno dopo il completamento di tre giorni successivi di irradiazione, trasferire i topi ai loro gabbie individuali VWRA descritte nel punto 2.1. </li><li> Record VWRA, come descritto al punto 2.2, tranne qui impostando la registrazionedurata a più di 15 giorni. Al termine dei 15 giorni, interrompere manualmente VWRA registrazione tramite l&#39;interfaccia software. NOTA: I dati di ciascun periodo di registrazione vengono automaticamente salvati come fogli di calcolo, ognuno dei quali comprende le rotazione, la distanza e le misurazioni di velocità per tutti gli animali (colonne) e in tutti gli intervalli (righe) per tutta la durata della registrazione. Alla fine dell&#39;esperimento, ci sono due fogli generati dal software di registrazione: uno per il VWRA pre-irradiazione, e uno per il VWRA post-irradiazione. </li></ol>

<ol>
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L., Barry, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stress+responses+of+rats+to+acute+body+or+neck+restraint.">Stress responses of rats to acute body or neck restraint.</a> Physiol Behav. 5 (4), 443-448 (1970).</li><li>Iwakawa, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Different+radiation+susceptibility+among+five+strains+of+mice+detected+by+a+skin+reaction.">Different radiation susceptibility among five strains of mice detected by a skin reaction.</a> J Radiat Res. 44 (1), 7-13 (2003).</li><li>Travis, E. L., Peters, L. J., McNeill, J., Thames, H. 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Questa ricerca è stata sostenuta dalla Divisione di Intramural Research, Istituto Nazionale di ricerca infermieristica, National Institutes of Health.

Abbiamo descritto un protocollo mediante irradiazione periferico mirati per indurre una riduzione di VWRA in topi senza confondere morbilità o mortalità. È importante sottolineare che un semplice dispositivo di schermatura permette di irradiazione in questo protocollo per indirizzare una regione desiderata in modo coerente, imitando i trattamenti di radiazione ricevuta dai pazienti con cancro pelvico. A differenza dei modelli CRF esistenti che coinvolgono il cervello o irradiazione corporea totale <...

Affaticamento cancro-correlata (CRF) è una condizione dolorosa e costosa, che spesso colpisce i pazienti che ricevono trattamenti contro il cancro 1. La fatica non è né proporzionale alla recente attività né alleviato dal riposo, ed è associata ad una vasta gamma di disturbi legati allo stato d&#39;animo, la motivazione, l&#39;attenzione e la cognizione 2. Le cause biologiche di CRF sono sconosciute, anche se è stato dimostrato in molti casi correlati con livelli di infiammazione e citochine, in alcuni casi con livelli di emoglobina e la funzione dei vari sistemi ormonali (vedi Saligan et al. 3 per una revisione della biologica studi di CRF). Studi controllati su modelli animali sono necessari per capire il comportamento e la biologia associata a questa condizione complessa. Mentre tumore legati 4 o chemioterapia connessi 5, 6 grassoIgue è stato studiato in modelli di roditori, l&#39;eziologia della CRF può essere specifico trattamento. Per indagare CRF relative a radioterapia, il nostro gruppo ha recentemente sviluppato un modello murino di irradiazione stanchezza indotta 7. A differenza dei modelli CRF esistenti che coinvolgono il cervello o irradiazione corporea totale 8, 9, questo modello esplora come un cambiamento nel comportamento in posizione centrale-driven, come la fatica, può essere attivato da una procedura di irradiazione perifericamente mirati. La procedura descritta qui è stato progettato per modellare radioterapia somministrata a pazienti con tumore pelvico, utilizzando schermatura di piombo per indirizzare la regione addominale inferiore / pelvica con irradiazione. Tuttavia, modificando la schermatura di piombo o la sua posizione rispetto agli animali da esperimento, questa procedura potrebbe essere adattato per modellare irradiazione di altre parti del corpo. Volontario attività ruota corsa (VWRA) viene utilizzato per misurare la fatica behavio simileR; perché è un comportamento volontario e normale 10, dovrebbe consentire l&#39;uso concomitante di altri test comportamentali e biologici. Abbiamo scoperto che l&#39;irradiazione periferica è sufficiente a ridurre VWRA nei topi senza causare morbilità palese 7. Esperimenti futuri con questo modello possono aiutare a rivelare effetti dell&#39;irradiazione periferico sul segnale biologico immunitario e altri, così come i cambiamenti a valle del sistema nervoso centrale che può produrre deficit associati CRF.

<table><tbody><tr><td>C57BL/6 Mice</td><td>Charles River</td><td></td><td>Strain code 027 (http://www.criver.com/products-services/basic-research/find-a-model/c57bl-6n-mouse)</td></tr><tr><td>Ketamine HCl</td><td>Putney</td><td></td><td>100 mg/mL stock solution</td></tr><tr><td>Xylazine HCl</td><td>Lloyd Laboratories</td><td></td><td>100 mg/mL stock solution</td></tr><tr><td>Rodent Tattoo System</td><td>AIMS</td><td>ATS-3</td><td>http://animalid.com/lab-animal-identification-systems/ats-3-general-rodent-tattoo-system</td></tr><tr><td>Lead Shielding Apparatus</td><td>(custom made)</td><td></td><td>One-inch thick lead shielding arranged as two boxes with a one-inch thick gap between them for targeted irradiation</td></tr><tr><td>Plexiglass shielding container</td><td>(custom made)</td><td></td><td>Plexiglass container filled with styrofoam. Styrofoam cutouts hold the lead shielding in place.</td></tr><tr><td>GammaCell 40 Exactor</td><td>Best Theratronics</td><td></td><td>http://www.theratronics.ca/product_gamma40.html</td></tr><tr><td>RAD Disk Ultra</td><td>Best Theratronics</td><td></td><td>http://www.theratronics.ca/product_rad.html</td></tr><tr><td>Mouse Single Activity Wheel Chamber</td><td>Lafayette Instrument Company</td><td>#80820</td><td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=980</td></tr><tr><td>Activity Wheel Counter for Computer Monitoring</td><td>Lafayette Instrument Company</td><td>#86061</td><td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1052</td></tr><tr><td>Modular Cable for Wheel Counters</td><td>Lafayette Instrument Company</td><td>#86051-7</td><td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1046</td></tr><tr><td>USB Computer Interface for Activity Wheel Counters</td><td>Lafayette Instrument Company</td><td>#86056A</td><td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1047</td></tr><tr><td>Activity Wheel Monitor Software</td><td>Lafayette Instrument Company</td><td>#86065</td><td>http://www.lafayetteneuroscience.com/product_detail.asp?itemid=1053</td></tr></tbody></table>

a mouse model of fatigue induced by peripheral irradiation

affaticamento cancro-correlata (CRF) è una condizione dolorosa e costosa, che spesso colpisce i pazienti che ricevono trattamenti contro il cancro, tra cui la radioterapia. Qui si descrive un metodo che utilizza irraggiamento periferico mirati per indurre comportamento a fatica, come nei topi. Con adeguata schermatura, l&#39;irraggiamento si rivolge la regione inferiore addominale / pelvica del mouse, risparmiando il cervello, nel tentativo di modellare il trattamento di radiazione ricevuta dagli individui con tumori pelvici. Forniamo una dose di irradiazione che è sufficiente per indurre comportamento a fatica, come nei topi, misurati con l&#39;attività ruota corsa volontaria (VWRA), senza provocare evidenti morbilità. Dal momento che ruota in esecuzione è un normale, comportamento volontario nei topi, il suo uso dovrebbe avere scarso effetto di confusione su altri test comportamentali o misure biologiche. Quindi, ruota in esecuzione può essere usato come misura di esito realizzabile nella comprensione dei correlati comportamentali e biologiche di fatica. CRF è una condizione complessa con frequenti comorbidità, e probabilmente ha cause legate sia al cancro e dei suoi vari trattamenti. I metodi descritti in questo documento sono utili per studiare variazioni indotte da radiazioni che contribuiscono allo sviluppo di CRF e, più in generale, per esplorare le reti biologiche che possono spiegare lo sviluppo e la persistenza di un comportamento perifericamente-triggered ma centralmente guidato come affaticamento .

Tre gruppi di topi sono stati eseguiti con il protocollo descritto sopra. Ci sono stati un totale di 16 sham e 20 irradiate (2.400 cGy, 3 x 800 / giorno cGy) topi. Dopo tre giorni consecutivi di irradiazione, il gruppo irradiato ha mostrato significativamente ridotto rispetto al VWRA farsa (misti misure ripetute ANOVA: effetto principale del trattamento di irradiazione, F 1,13 = 19,233, p &lt;0.001). L&#39;effetto è significativo per i primi sette giorni dopo l&#39;irraggiame...

Watch this Scientific Journal Video about A Mouse Model of Fatigue Induced by Peripheral Irradiation at JoVE.com

A Mouse Model of Fatigue Induced by Peripheral Irradiation

Descriviamo un metodo che utilizza irraggiamento periferico mirati per indurre comportamento a fatica, come nei topi. La dose di irradiazione non letale selezionati porta ad una riduzione di una settimana in attività di ruote in esecuzione volontaria.

Un modello murino di fatica indotta da irradiazione Peripheral

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. ...

a-mouse-model-of-fatigue-induced-by-peripheral-irradiation

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Cancer Research

7.8K Views.  National Institutes of Health.  Descriviamo un metodo che utilizza irraggiamento periferico mirati per indurre comportamento a fatica, come nei topi. La dose di irradiazione non letale selezionati porta ad una riduzione di una settimana in attività di ruote in esecuzione volontaria. 

Video: A Mouse Model of Fatigue Induced by Peripheral Irradiation

Fluorescent Orthotopic Mouse Model of Pancreatic Cancer

Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will survive longer than five years. In order to understand and mimic the microenvironment of pancreatic tumors, we utilized a murine orthotopic model of pancreatic cancer that allows non-invasive imaging of tumor progression in real time. Pancreatic cancer cells expressing green fluorescent protein (PANC-1 GFP) were suspended in basement membrane matrix, high concentration, (e.g., Matrigel HC) with serum-free media and then injected into the tail of the pancreas via laparotomy. The cell suspension in the high concentration basement membrane matrix becomes a gel-like substance once it reaches room temperature; therefore, it gels when it comes in contact with the pancreas, creating a seal at the injection site and preventing any cell leakage. Tumor growth and metastasis to other organs are monitored in live animals by using fluorescence. It is critical to use the appropriate filters for excitation and emission of GFP. The steps for the orthotopic implantation are detailed in this article so researchers can easily replicate the procedure in nude mice. The main steps of this protocol are preparation of the cell suspension, surgical implantation, and whole body fluorescent in vivo imaging. This orthotopic model is designed to investigate the efficacy of novel therapeutics on primary and metastatic tumors.

A procedure to implant green fluorescent protein-expressing pancreatic cancer cells (PANC-1 GFP) orthotopically into the pancreas of Balb-c Ola Hsd-Fox1nu mice to assess tumor progression and metastasis is presented here.

Fluorescente ortotopico modello murino di cancro al pancreas

Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will ...

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Ricerca sul cancro

Evaluating the Role of Mitochondrial Function in Cancer-related Fatigue

Fatigue is a common and debilitating condition that affects most cancer patients. To date, fatigue remains poorly characterized with no diagnostic test to objectively measure the severity of this condition. Here we describe an optimized method for assessing mitochondrial function of PBMCs collected from fatigued cancer patients. Using a compact extracellular flux system and sequential injection of respiratory inhibitors, we examined PBMC mitochondrial functional status by measuring basal mitochondrial respiration, spare respiratory capacity, and energy phenotype, which describes the preferred energy pathway to respond to stress. Fresh PBMCs are readily available in the clinical setting using standard phlebotomy. The entire assay described in this protocol can be completed in less than 4 hours without the involvement of complex biochemical techniques. Additionally, we describe a normalization method that is necessary for obtaining reproducible data. The simple procedure and normalization methods presented allow for repeated sample collection from the same patient and generation of reproducible data that can be compared between time points to evaluate potential treatment effects.

Our goal was to develop a practical protocol to evaluate mitochondrial dysfunction associated with fatigue in cancer patients. This innovative protocol is optimized for clinical use involving only standard phlebotomy and basic laboratory procedures.

Valutare il ruolo della funzione mitocondriale in affaticamento legato al cancro

Fatigue is a common and debilitating condition that affects most cancer patients. To date, fatigue remains poorly characterized with no diagnostic test to ...

The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of current interventions to adequately treat fatigue in all patients leaves a need for new treatment options. Despite the therapeutic need and importance of preclinical research in helping identify promising novel treatments, few preclinical assays of fatigue are available. Moreover, the most common preclinical assay used to assess fatigue-like behavior, voluntary wheel running, is not suitable for use with some strains of mice, may not be sensitive to drugs that reduce fatigue, and has relatively low throughput. The current protocol describes a novel, non-voluntary preclinical assay of fatigue-like behavior, the treadmill fatigue test, and provides evidence of its efficacy in detecting fatigue-like behavior in mice treated with a chemotherapy drug known to cause fatigue in humans and fatigue-like behavior in animals. This assay may be a beneficial alternative to wheel running, as fatigue-like behavior and potential interventions can be assessed in a greater number of mice over a shorter time frame, thus permitting faster discovery of new therapeutic options.

Fatigue is a common, undertreated and frequently poorly-understood symptom in many diseases and disorders. New preclinical assays of fatigue may help to improve current understanding and future treatment of fatigue. To that end, the current protocol provides a novel means of measuring fatigue-like behavior in the mouse.

Il tapis roulant fatica di prova: un test semplice, high-throughput di stanchezza simile comportamento per il mouse

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of ...

Comportamento

Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition

The functional characterization of adult-born neurons remains a significant challenge. Approaches to inhibit adult neurogenesis via invasive viral delivery or transgenic animals have potential confounds that make interpretation of results from these studies difficult. New radiological tools are emerging, however, that allow one to noninvasively investigate the function of select groups of adult-born neurons through accurate and precise anatomical targeting in small animals. Focal ionizing radiation inhibits the birth and differentiation of new neurons, and allows targeting of specific neural progenitor regions. In order to illuminate the potential functional role that adult hypothalamic neurogenesis plays in the regulation of physiological processes, we developed a noninvasive focal irradiation technique to selectively inhibit the birth of adult-born neurons in the hypothalamic median eminence. We describe a method for Computer tomography-guided focal irradiation (CFIR) delivery to enable precise and accurate anatomical targeting in small animals. CFIR uses three-dimensional volumetric image guidance for localization and targeting of the radiation dose, minimizes radiation exposure to nontargeted brain regions, and allows for conformal dose distribution with sharp beam boundaries. This protocol allows one to ask questions regarding the function of adult-born neurons, but also opens areas to questions in areas of radiobiology, tumor biology, and immunology. These radiological tools will facilitate the translation of discoveries at the bench to the bedside.

The function of adult-born mammalian neurons remains an active area of investigation. Ionizing radiation inhibits the birth of new neurons. Using computer tomography-guided focal irradiation (CFIR), three-dimensional anatomical targeting of specific neural progenitor populations can now be used to assess the functional role of adult neurogenesis.

Interrogatorio funzionale di età ipotalamico neurogenesi con focale Radiological inibizione

The functional characterization of adult-born neurons remains a significant challenge. Approaches to inhibit adult neurogenesis via invasive viral ...

Neuroscienze

Establishment of a Robust and Reproducible Model of Radiation-Induced Skin and Muscle Fibrosis

Radiation-induced skin fibrosis (RISF) can result from a plethora of scenarios including cancer therapy, accidental exposure, or acts of terrorism. Radioactive beams can penetrate through the skin and affect the structures in their path including skin, muscles, and internal organs. Skin is the first structure to get exposed to radiation and is susceptible to develop chronic fibrosis, which is challenging to treat. Currently, limited treatment options show moderate efficacy in mitigating radiation-related skin fibrosis. A key factor hindering the development of effective countermeasures is the absence of a convenient and robust model that could allow for translation of the experimental findings to humans. Here, a robust and reproducible murine hind limb skin fibrosis model has been established for prophylactic and therapeutic evaluation of possible agents for functional and molecular recovery.
The right hind limb was irradiated using a single dose of 40 (Gray) Gy to induce skin fibrosis. Subjects developed edema and dermatitis in the early stages proceeded by visible skin constriction. Irradiated limbs showed a significantly reduced limb range of motion in the following weeks. In late stages, acute side effects subsided, yet chronic fibrosis persisted. A gait index was performed as an additional functional assay, which demonstrated the development of functional impairment. These non-invasive methods demonstrated reliable measurements for tracing fibrosis progression, which is supported by histological analyses. The radiation dose, application, and post-irradiation analyses employed in this model offer a vigorous and reproducible method for studying radiation-induced skin fibrosis and testing the efficacy of therapeutical agents.

Here we present a protocol to induce radiation-induced skin fibrosis in the hind limb of mice and perform post-irradiation measurements of chronic impairment via limb excursion and gait index analyses to evaluate the functional outcome. The model elucidates radiation-related skin fibrosis mechanisms and is useful in subclinical therapeutic studies.

Radiation-induced skin fibrosis (RISF) can result from a plethora of scenarios including cancer therapy, accidental exposure, or acts of terrorism. ...

Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model

Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and negatively impact patient quality of life and long term survival. Advances in the understanding of the biological pathways associated with normal tissue toxicities have allowed for the development of interventional drugs, however, current response studies are limited by a lack of quantitative metrics for assessing the severity of skin reactions. Here we present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe the instrumentation design of the DOS system as well as the inversion algorithm for extracting the optical parameters. Finally, to demonstrate clinical utility, we present representative data from a pre-clinical mouse model of radiation induced erythema and compare the results with a commonly employed visual scoring. The described DOS method offers an objective, high through-put evaluation of skin toxicity via functional response that is translatable to the clinical setting.

We present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe DOS instrumentation design, optical parameters extraction algorithms and the animal handling procedures required to yield representative data from a pre-clinical mouse model of radiation induced erythema.

Diffuse spettroscopia ottica per la valutazione quantitativa di acuta radiazioni ionizzanti tossicità cutanee indotte Utilizzando un modello di topo

Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and ...

Medicina

A Rat Model of Central Fatigue Using a Modified Multiple Platform Method

In this article, we introduced a rat model of central fatigue using the modified multiple platform method (MMPM). The Multiple Platform box was designed as a water tank with narrow platforms on the bottom. The model rats were put into the tank and stood on the platforms for 14 h (18:00 - 8:00) per day for a consecutive 21 days, with a blank control group set for contrast. At the end of modeling, rats in the model group showed an obvious fatigued appearance. To assess the model, we performed several behavioral tests, including the open field test (OFT), the elevated plus maze (EPM) test, and the exhaustive swimming (ES) test. The results showed that anxiety, spatial cognition impairment, poor muscle performance, and declined voluntary activity presented in model rats confirm the diagnosis of&#160;central fatigue. Changes of the central neurotransmitters also verified the result. In conclusion, the model successfully simulated central fatigue, and future study with the model may help reveal the pathological mechanism of the disease.

Here, we present a protocol to introduce a rat model of central fatigue using the modified multiple platform method (MMPM).

Un ratto di modello di affaticamento centrale utilizzando una versione modificata più piattaforma metodo

In this article, we introduced a rat model of central fatigue using the modified multiple platform method (MMPM). The Multiple Platform box was designed ...

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 modello preclinico di colpo di calore da sforzo nei topi

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

Metodo Shocktube per modellare esplosioni di basso livello altamente ripetitive nei topi

Modeling Highly Repetitive Low-level Blast Exposure in Mice

Exposure to explosive blasts is a significant risk factor for brain trauma among exposed persons. Although the effects of large blasts on the brain are well understood, the effects of smaller blasts such as those that occur during military training are less understood. This small, low-level blast exposure also varies highly according to military occupation and training tempo, with some units experiencing few exposures over the course of several years whereas others experience hundreds within a few weeks. Animal models are an important tool in identifying both the injury mechanisms and long-term clinical health risks following low-level blast exposure. Models capable of recapitulating this wide range of exposures are necessary to inform acute and chronic injury outcomes across these disparate risk profiles.
Although outcomes following a few low-level blast exposures are easily modeled for mechanistic study, chronic exposures that occur over a career may be better modeled by blast injury paradigms with repeated exposures that occur frequently over weeks and months. Shown here are methods for modeling highly repetitive low-level blast exposure in mice. The procedures are based on established and widely used pneumatic shocktube models of open-field blast exposure that can be scaled to adjust the overpressure parameters and the number or interval of the exposures. These methods can then be used to either enable mechanistic investigations or recapitulate the routine blast exposures of clinical groups under study.

Autore in primo piano: Decifrare gli effetti a lungo termine delle esposizioni a bassi livelli di esplosioni nei topi

Presented here are methods for producing repeated low-intensity blast exposures using mice.

Modellazione dell'esposizione altamente ripetitiva a basse esplosioni nei topi

Exposure to explosive blasts is a significant risk factor for brain trauma among exposed persons. Although the effects of large blasts on the brain are ...

Un modello murino di fatica indotta da irradiazione Peripheral

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Fluorescente ortotopico modello murino di cancro al pancreas

Valutare il ruolo della funzione mitocondriale in affaticamento legato al cancro

Il tapis roulant fatica di prova: un test semplice, high-throughput di stanchezza simile comportamento per il mouse

Interrogatorio funzionale di età ipotalamico neurogenesi con focale Radiological inibizione

Establishment of a Robust and Reproducible Model of Radiation-Induced Skin and Muscle Fibrosis

Diffuse spettroscopia ottica per la valutazione quantitativa di acuta radiazioni ionizzanti tossicità cutanee indotte Utilizzando un modello di topo

Un ratto di modello di affaticamento centrale utilizzando una versione modificata più piattaforma metodo

Un modello preclinico di colpo di calore da sforzo nei topi

Modellazione dell'esposizione altamente ripetitiva a basse esplosioni nei topi

Modellazione dell'esposizione altamente ripetitiva a basse esplosioni nei topi