血腦屏障相關(guān)知識(shí)課件(與“知識(shí)”有關(guān)的文檔共15張)

血腦屏障相關(guān)知識(shí)課件第一頁，共15頁。KeyfunctionsoftheBBBDiscoveryoftheblood-brainbarrier

Anatomyoftheblood-brainbarrier

Circumventricularorgans

Factorsthatcanlowertheblood-brainbarrier

Blood-brainborderandGlucoseBlood-brainbarrierpermeabilityinthemousebrain

Outline第二頁，共15頁。KeyfunctionsoftheBBB

Amechanismthatcontrolsthepassageofsubstancesfromthebloodintothecerobrospinalfluidandthusintothebrainandspinalcord.Theblood-brainbarrier(BBB)letsessentialmetabolites,suchasoxygenandglucose,passfromthebloodtothebrainandcentralnervoussystem(CNS)butblocksmostmoleculesthataremoremassivethanabout500daltons.ThisisalowmassinbiomoleculartermsandmeansthateverythingfromhormonesandneurotransmitterstovirusesandbacteriaarerefusedaccesstothebrainbytheBBB.Italsomeansthatmanydrugs,whichwouldotherwisebecapableoftreatingdisordersoftheCNS,aredeniedaccesstotheveryregionswheretheywouldbeaffective.

第三頁，共15頁。KeyfunctionsoftheBBBare:

Protectingthebrainfrom"foreignsubstances"(suchasvirusesandbacteria)inthebloodthatcouldinjurethebrainShieldingthebrainfromhormonesandneurotransmittersintherestofthebodyMaintainingaconstantenvironment(homeostasis)forthebrain第四頁，共15頁。Discoveryoftheblood-brainbarrierThespecialpropertiesoftheblood-brainbarrierwerefirstobservedinthelate19thcenturybytheGermanbacteriologistPaulEhrlich.Hefoundthatwhenheinjectedcoloreddyesintothebloodstreamtheyleakedoutofcapillariesinmostregionsofthebodytostainthesurroundingtissues;thebrain,however,remainedunstained.Ehrlichwronglysurmisedthatthebrainhadalowaffinityforthedyes.Itwashisstudent,EdwinGoldman,whodidtheotherhalfoftheexperimentandrealizedthetruthofwhatwasgoingon.Goldmaninjectedadyeintothecerebrospinalfluidthatsurroundsthebrainandobservedthatitstainedthebrain,butnothingelse.Goldmanncorrectlyconcludedthatthedyewasunabletocrossthespecializedwallsofbraincapillaries.第五頁，共15頁。Anatomyoftheblood-brainbarrierDiagramoftheblood-brainbarriertransversetoacapillary

第六頁，共15頁。(A)Diagramofabraincapillaryincrosssectionandreconstructedviews,showingendothelialtightjunctionsandtheinvestmentofthecapillarybyastrocyticendfeet.(B)Electronmicrographofboxedareain(A),showingtheappearanceoftightjunctionsbetweenneighboringendothelialcells(arrows).(AafterGoldstein,GoldsteinandBetz,1986;BfromPetersetal.,1991.)Anatomyoftheblood-brainbarrier第七頁，共15頁。第八頁，共15頁。Circumventricularorgans

Thecircumventricularorgansareregionsofthebrainwheretheblood-barrierbarrierisweak.Theseregionsallowssubstancestocrossintobraintissuemorefreelyandtherebyallowthebraintomonitorthemakeupoftheblood.

第九頁，共15頁。VariousfactorsandconditionscanleadtoaloweringoftheBBB.Theseinclude:Hypertension(highbloodpressure)Hyperosmolitity(ahighconcentrationofasubstanceintheblood)MicrowavesRadiationInfectionInjurytothebrainduetotrauma,ischemia,inflammation,orpressureAdditionally,theBBBisnotfullyformedatbirth.

Factorsthatcanlowertheblood-brainbarrier

第十頁，共15頁。Blood-brainborderandGlucoseTometabolizeglucoseinthebrain,ortoperformcerebralglucosemetabolism,requiresacomplex,multi-stepprocessinwhichthesugaristransportedintothebrain--breakingthewellwalledblood-brainborder,convertedtoanothersubstance,completesasetofchemicalreactions,andthenultimatelyoxidizedtocarbondioxideandwaterforthefulluseofitasenergy.

Blood-brainbarrier第十一頁，共15頁。Blood-brainbarrierpermeabilityinthemousebrainMasakiUeno.ActaNeuropathol(2004)107:532–538第十二頁，共15頁。Blood-brainbarrierpermeabilityintheratbrainFig.2A–FLightmicroscopicphotographsshowingthestainingforHRPwithTMBinWKY(AandD),SHR(BandE),andSHRSP(CandF).D,E,andFarehigher-powermagnificationsofthestainingforHRPwithTMBinthehippocampalareaindicatedbyarrowsinA,B,andC,respectively.NoHRPstainingisobservedinthehippocampusandcortexofWKY(AandD).ThestainingforHRPisseeninthehippocampus,especiallyaroundvessels(E,F:arrows)alongtheh