Name: a mouse model of fatigue induced by peripheral irradiation
Uploaded: 2017-03-17T14:00:00
Description: Watch this Scientific Journal Video about A Mouse Model of Fatigue Induced by Peripheral Irradiation at JoVE.com

Forfatterne vil gerne takke Michele Allen for National Heart, Lung, og Blood Institute (NHLBI) af National Institutes of Health (NIH) for generøst deler hendes ekspertise i murine fænotypebestemmelse metoder og for hendes fortsatte teknisk bistand, samt for Timothy Hunt af NHLBI for at hjælpe os med at udvikle afskærmning enhed. Denne undersøgelse er støttet af afdelingen for Intramural Research af Det Nationale Institut for Sygeplejeforskning af NIH, og en del af valideringen forsøg støttet af en bevilling fra Oncology Nursing Society Foundation.

Etik Statement: Denne undersøgelse blev godkendt af National Institutes of Health (NIH) Animal Care og brug Udvalg. Alle efterforskere, der deltager i håndtering af dyr og måling af undersøgelsens resultater blev ordentligt uddannet af NIH Office of Animal Care og brug og National Heart, Lung, og Blood Institute Murine Fænotype Core. Alle aspekter af dyreforsøg, bolig, og miljømæssige betingelser, der anvendes i denne undersøgelse var i overensstemmelse med Vejledning for Pleje og anvendelse af forsøgsdyr <sup...

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Vi har beskrevet en protokol ved hjælp målrettet perifer bestråling til at fremkalde en reduktion af VWRA i mus uden confounding sygelighed eller dødelighed. Vigtigere er det, en simpel afskærmning enhed giver bestråling i denne protokol til at målrette en ønsket region konsekvent, efterligner strålebehandlinger modtaget af patienter med bækken kræft. I modsætning til eksisterende CRF modeller, der involverer hjernen eller bestråling af hele legemet 8, 9,...

Kræft-relaterede træthed (CRF) er en foruroligende og bekostelig tilstand, der ofte påvirker patienter, der fik kræftbehandling 1. Den træthed hverken proportional med seneste aktivitet eller lindres ved hvile, og det er forbundet med en lang række forstyrrelser relateret til humør, motivation, opmærksomhed og kognition 2. De biologiske årsager til CRF er ukendte, selvom det er blevet vist i mange tilfælde at korrelere med inflammation og cytokinniveauer, også i nogle tilfælde med hæmoglobinniveau og funktionen af forskellige hormonsystemer (se Saligan et al. 3 for en gennemgang af den biologiske undersøgelser af CRF). Kontrollerede undersøgelser med dyremodeller er nødvendige for at forstå den adfærd og biologi er forbundet med denne komplekse tilstand. Mens tumorrelateret 4 eller kemoterapi-beslægtet 5, 6 fedtigue er blevet undersøgt i gnavermodeller kan ætiologien af ​​CRF være behandling-specifik. For at undersøge CRF relateret til strålebehandling har vores gruppe for nylig udviklet en musemodel for bestråling-induceret træthed 7. I modsætning til eksisterende CRF modeller, der involverer hjernen eller bestråling af hele legemet 8, 9, denne model undersøger, hvordan en ændring i centralt drevne adfærd, ligesom træthed, kan udløses af en perifert målrettet bestråling procedure. Den her beskrevne procedure er designet til at modellere strålebehandling administreret til patienter med bækkensmerter cancer, ved anvendelse blyafskærmning til at målrette den nedre abdominale / bækkenpartiet med bestråling. Men ved at modificere blyafskærmning eller dens placering i forhold til forsøgsdyr, denne procedure kan tilpasses til at modellere bestråling af andre dele af kroppen. Frivillig hjul-kører aktivitet (VWRA) bruges til at måle træthed-lignende behavior; fordi det er en frivillig og normal adfærd 10, bør den gøre det muligt samtidig brug af andre adfærdsmæssige og biologiske tests. Vi har fundet, at perifer bestråling er tilstrækkelig til at reducere VWRA i mus uden at forårsage åbenlys sygelighed 7. Fremtidige eksperimenter med denne model kan hjælpe afsløre virkningen af ​​perifer bestråling på immun- og andre biologisk signalering, samt de efterfølgende ændringer i centralnervesystemet, der kan producere mangler forbundet med CRF.

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a mouse model of fatigue induced by peripheral irradiation

Cancer-relateret træthed (CRF) er et rystende og bekostelig tilstand, der ofte påvirker patienter, der modtager cancer behandlinger, herunder strålebehandling. Her beskriver vi en fremgangsmåde under anvendelse målrettet perifer bestråling for at inducere træthed-lignende opførsel hos mus. Med passende afskærmning, bestrålingen målretter lavere abdominal / bækkenpartiet af musen, skåner hjernen, i et forsøg på at modellere strålebehandling modtages af personer med bækken cancere. Vi leverer en strålingsdosis, der er tilstrækkelig til at inducere træthed-lignende opførsel hos mus, målt ved frivillig hjul-running aktivitet (VWRA), uden at forårsage åbenbar morbiditet. Da hjulet kører er en normal, frivillig adfærd hos mus, bør dens anvendelse har ringe confounding effekt på andre adfærdsmæssige test eller biologiske foranstaltninger. Derfor kan hjulet kører anvendes som en gennemførlig endepunkt i at forstå de adfærdsmæssige og biologiske korrelater for træthed. CRF er en kompleks tilstand med hyppige cofølgesygdomme, og sandsynligvis har årsager i forbindelse med såvel kræft og dens forskellige behandlinger. Beskrevet i dette papir metoder er nyttige til undersøgelse stråling-induceret ændringer, der bidrager til udviklingen af ​​CRF og mere generelt, at udforske de biologiske netværk, der kan forklare udviklingen og persistens af et perifert-udløst, men centralt drevet adfærd som træthed .

Tre batcher af mus blev kørt gennem forskrift ovenfor beskrevet. Der var i alt 16 sham og 20 bestrålede (2.400 cGy, 3 x 800 cGy / dag) mus. Efter tre dage i træk af bestråling, viste det bestrålede gruppe væsentligt reduceret VWRA sammenlignet med sham (blandede gentagne målinger ANOVA: væsentligste virkning af strålebehandling, F 1,13 = 19,233, p &lt;0,001). Effekten var signifikant for de første syv dage efter bestråling (simple vigtigste virkninger, p &lt;0,05 me...

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

Vi beskriver en fremgangsmåde under anvendelse målrettet perifer bestråling for at inducere træthed-lignende opførsel hos mus. Den valgte ikke-dødelige strålingsdosis fører til en ugelang reduktion i frivilligt hjul-kører aktivitet.

En mus Model af træthed induceret af perifere Bestråling

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

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