critical role of p2x7 receptors in the neuroinflammation and cognitive dysfunction after surgery 2017 bin zheng-匠人.pdf

该【critical role of p2x7 receptors in the neuroinflammation and cognitive dysfunction after surgery 2017 bin zheng-匠人 】是由【刘备文库】上传分享，文档一共【34】页，该文档可以免费在线阅读，需要了解更多关于【critical role of p2x7 receptors in the neuroinflammation and cognitive dysfunction after surgery 2017 bin zheng-匠人 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。:..AcceptedManuscriptCriticalroleofP2X7receptorsintheneuroinflammationandcognitivedys-functionaftersurgeryBinZheng,RenchunLai,JunLi,ZhiyiZuoPII:S0889-1591(17)30005-3DOI:http://dx./.:YBRBI3064Toappearin:Brain,Behavior,andImmunityReceivedDate:10August2016RevisedDate:22December2016AcceptedDate:8January2017Pleasecitethisarticleas:Zheng,B.,Lai,R.,Li,J.,Zuo,Z.,CriticalroleofP2X7receptorsintheneuroinflammationandcognitivedysfunctionaftersurgery,Brain,Behavior,andImmunity(2017),doi:http://dx./.,typesetting,,andalllegaldisclaimersthatapplytothejournalpertain.:..CriticalroleofP2X7receptorsintheneuroinflammationandcognitivedysfunctionaftersurgeryBinZhenga,b,RenchunLaia,c,JunLiaandZhiyiZuoa,daDepartmentofAnesthesiology,UniversityofVirginia,Charlottesville,VA22908,,GuangzhouFirstPeople?sHospital,GuangzhouMedicalUniversity,Guangzhou,Guangdong510180,ChinacDepartmentofAnesthesiologyandStateKeyLaboratoryofOncologyinSouthChinaandCollaborativeInnovationCenterofCancerMedicine,SunYat-SenUniversityCancerCenter,Guangzhou,Guangdong510060,ChinadDepartmentofAnesthesiology,SunYat-SenMemorialHospital,SunYat-SenUniversity,Guangzhou,Guangdong510120,ChinaRunningtitle:P2X7receptorsandcognitiveimpairmentaftersurgeryAddresscorrespondenceto:,DepartmentofAnesthesiology,UniversityofVirginiaHealthSystem,1HospitalDrive,POBox800710,Charlottesville,Virginia22908-:434-924-2283,Fax:434-924-2105,e-mail:******@:Thisstudywassupportedbygrants(R01GM098308andR21AG047472toZZuo)fromtheNationalInstitutesofHealth,Bethesda,MD,byagrantfromtheInternationalAnesthesiaResearchSociety(2007FrontiersinAnesthesiaResearchAwardtoZZuo),Cleveland,OH,,UniversityofVirginia,Charlottesville,VAandagrant(81641160)fromNationalNaturalScienceFoundationofChina,Beijing,::..,proteinsthatparticipateininflammatoryresponse,intheneuroinflammationinductionaftersurgery,-weekoldC57BL/%isoflurane,%sevofluraneor10%,,,butnotbydesflurane,-:learningandmemory;neuroinflammation;P2X7receptors;volatileanesthetics2:..(POCD)isarecognizedclinicalsyndrome(Baranovetal.,2009).ursaftercardiacandnon-cardiacsurgery(Molleretal.,1998;Monketal.,2008;al.,2001).POCDnotonlyaffectsthedailylifeofpatientsbutalsoisassociatedwithincreasedmortalitywithinoneyearaftersurgery(Monketal.,2008;Steinmetzetal.,2009).Thus,(Caoetal.,2012;Cibellietal.,2010;Terrandoetal.,2011;Zhangetal.,2014a;Zhangetal.,2014b).Thereisalsoevidenceurrenceofneuroinflammationaftersurgeryinhuman(Tangetal.,2011).However,(al.,2011).Theyarepurinergicreceptorsthatareinotropicligand-gatednon-(Burnstock,2006).TheactivationofP2X7receptorsfacilitatestheformationofinflammasome,(IL)-1βandIL-18,importantproinflammatorycytokines(al.,2011;Karmakaretal.,2015;Latzetal.,2013).IthasbeenaconsistentfindingthatactivationofP2X7receptorsreleasesIL-1βandIL-18frommicrogliainthebrain,althoughotherinflammatorymediators,suchasIL-6,,P2X7receptorsareintimatelyinvolvedinneuroinflammationandinhibitingtheactivationofthesereceptorshasbeenproposedasatherapeuticmethodforvariousdiseasesinthebrain,suchasstrokeandneurodegenerativediseases,inwhichneuroinflammationplaysadetrimentalrole(BhattacharyaandBiber,2016).WeandothershaveshownthatIL-1βplaysacriticalroleinanesthesiaandsurgery-inducedcognitivedysfunction(Caoetal.,2012;Cibellietal.,2010;LinandZuo,2011).Thus,wehypothesizethat3:..,BrilliantBlueG(BBG)(Jiangetal.,2000),(Caoetal.,2012;Zhangetal.,2014a).However,ratsthathadcarotidarterialexposureunderisofluraneorpropofolanesthesiahadasimilardegreeofneuroinflammationandcognitivedysfunction(Zhangetal.,2015),,isoflurane,sevofluraneanddesflurane,(Zhangetal.,2012)andlessdisruptionofintracellularcalciumhomeostasisthanisoflurane(Yangetal.,2008).AlthoughanearlystudyshowedthatisofluraneandsevofluranedidnotaffecttheactivityofP2X7receptors(Nakanishietal.,2007),arecentstudyshowedthatisofluraneactivatedP2X7receptorsinrathippocampalneurons(Liuetal.,2013).,,wecomparedthedegreeofneuroinflammationandcognitivedysfunctionofmiceundersurgicallevelofisoflurane,:..(Charlottesville,VA).AllanimalordancewiththeNationalInstitutesofHealthGuidefortheCareandUseofLaboratoryAnimals(NIHpublicationsnumber80-23)-weekoldmaleC57BL/6Jmiceweighing23?26gfromCharlesRiverLaboratoriesInternational(Wilmington,MA)wererandomlyassignedtothefollowinggroups:(1)control,(2)%isoflurane,(3)%sevoflurane,and(4)surgeryunderanesthesiawith10%-,themicewererandomlyassignedtothefollowinggroups:(1)control,(2)BrilliantBlueG(BBG)injection,(3)%isofluraneplussalineinjection,and(4)%,eight-weekoldmaleP2X7-/-miceweighing22?25gfromtheJacksonLaboratory(BarHarbor,Maine)wererandomlyassignedtotwogroups:(1)controland(2)%,,24hor7daysafterthesurgeryforELISA,(al.,2016).Briefly,%isoflurane,%sevofluraneor10%hatwere5:..deliveredbyanesthetic-(Ichinoseetal.,1998;Sonneretal.,1999).oncentrationsweremonitoredwithaDatex?infraredanalyzer(Capnomac,Helsinki,Finland).Duringtheprocedure,-,,,rectaltemperaturewasmonitoredandmaintainedat37°Cwiththeaidofservo-controlledwarmingblanket(TCAT-2LV,Physitempinstruments,Clifton,NJ).Mouse?sheartrateandpulseoxygensaturationweremonitoredcontinuouslybyMouseOXMurinePlusOximeterSystem(StarrLifeSciencesCorporation,Oakmont,PA).Animalsinthecontrolgroupofallthreesetsofexperimentsdidnotreceiveanesthesia,(Sigma-Aldrich,,MO)waspreparedfreshlyeachdaybydissolvingthepowderinnormalsalineandinjectedintraperitoneallyat50mg/kg/,(Kimbleretal.,2012).,theanimalsweresubjectedtoBarnesmazeaswe6:..previouslydescribed(al.,2016)(SDInstruments,SanDiego,CA).(85dB)andbrightlight(200W),-termretentiononday5andlong--Mazevideotrackingsystem(SDInstruments,SanDiego,CA).,miceweresubjectedtofearconditioningtestaswepreviouslydescribed(al.,2016).Eachmousewasplacedintoatestchamberwipedwith70%alcoholandexposedto3tone-footshockpairings(tone:2000Hz,85db,30s;footshock:,2s)%,eachcyclefor30sfollowedby1-mininter-cycleinterval().