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1、AdvancedDrugDeliveryReviews64(2012)629–639ContentslistsavailableatSciVerseScienceDirectAdvancedDrugDeliveryReviewsjournalhomepage:www.elsevier.com/locate/addrDrugdeliverytothebraininAlzheimer'sdisease:Considerationoftheblood–brainbarrier☆WilliamA.Banks⁎GeriatricResearch,Education
2、,andClinicalCenter,VeteransAffairsPugetSoundHealthCareSystem,Seattle,WA,USADivisionofGerontologyandGeriatricMedicine,DepartmentofInternalMedicine,UniversityofWashingtonSchoolofMedicine,Seattle,WA,USAarticleinfoabstractArticlehistory:ThesuccessfultreatmentofAlzheimer'sdisease(AD)w
3、illrequiredrugsthatcannegotiatetheblood–brainReceived3August2011barrier(BBB).However,theBBBisnotsimplyaphysicalbarrier,butacomplexinterfacethatisinintimateAccepted9December2011communicationwiththerestofthecentralnervoussystem(CNS)andinfluencedbyperipheraltissues.Availableonline17D
4、ecember2011ThisreviewexaminesthreeaspectsoftheBBBinAD.First,itconsidershowtheBBBmaybecontributingtotheonsetandprogressionofAD.Inthisregard,theBBBitselfisatherapeutictargetinthetreatmentofKeywords:AD.Second,itexamineshowtheBBBrestrictsdrugsthatmightotherwisebeusefulinthetreatmento
5、fADBlood–brainbarrierAlzheimer'sdiseaseandexaminesstrategiesbeingdevelopedtodeliverdrugstotheCNSforthetreatmentofAD.Third,itcon-DrugdeliverysidershowdrugpenetrationacrosstheADBBBmaydifferfromtheBBBofnormalaging.Inthiscase,thoseCerebrospinalfluiddifferencescancomplicatethetreatment
6、ofCNSdiseasessuchasdepression,delirium,psychoses,andpainBiologicalscontrolintheADpopulation.PeptidesPublishedbyElsevierB.V.RegulatoryproteinsTransportTransmembranediffusionP-glycoproteinContents1.Introduction:thespecterofAlzheimer'sdisease.........................................
7、....6302.DefinitionsoftheBBBanditsgeneralrelationtodrugdelivery......................................6303.TheBBBasacauseofADandtherapeutictarget.............................................6313.1.BBBdisruption.........................................................6313.2.Decrease
8、dcerebrovascularbloodflowanduptakeofoxyge
