血腦屏障相關(guān)知識課件

血腦屏障相關(guān)知識課件第1頁，課件共15頁，創(chuàng)作于2023年2月KeyfunctionsoftheBBBDiscoveryoftheblood-brainbarrier

Anatomyoftheblood-brainbarrier

Circumventricularorgans

Factorsthatcanlowertheblood-brainbarrier

Blood-brainborderandGlucoseBlood-brainbarrierpermeabilityinthemousebrain

Outline第2頁，課件共15頁，創(chuàng)作于2023年2月KeyfunctionsoftheBBB

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

第3頁，課件共15頁，創(chuàng)作于2023年2月KeyfunctionsoftheBBBare:

Protectingthebrainfrom"foreignsubstances"(suchasvirusesandbacteria)inthebloodthatcouldinjurethebrainShieldingthebrainfromhormonesandneurotransmittersintherestofthebodyMaintainingaconstantenvironment(homeostasis)forthebrain第4頁，課件共15頁，創(chuàng)作于2023年2月Discoveryoftheblood-brainbarrierThespecialpropertiesoftheblood-brainbarrierwerefirstobservedinthelate19thcenturybytheGermanbacteriologistPaulEhrlich.Hefoundthatwhenheinjectedcoloreddyesintothebloodstreamtheyleakedoutofcapillariesinmostregionsofthebodytostainthesurroundingtissues;thebrain,however,remainedunstained.Ehrlichwronglysurmisedthatthebrainhadalowaffinityforthedyes.Itwashisstudent,EdwinGoldman,whodidtheotherhalfoftheexperimentandrealizedthetruthofwhatwasgoingon.Goldmaninjectedadyeintothecerebrospinalfluidthatsurroundsthebrainandobservedthatitstainedthebrain,butnothingelse.Goldmanncorrectlyconcludedthatthedyewasunabletocrossthespecializedwallsofbraincapillaries.第5頁，課件共15頁，創(chuàng)作于2023年2月Anatomyoftheblood-brainbarrierDiagramoftheblood-brainbarriertransversetoacapillary

第6頁，課件共15頁，創(chuàng)作于2023年2月(A)Diagramofabraincapillaryincrosssectionandreconstructedviews,showingendothelialtightjunctionsandtheinvestmentofthecapillarybyastrocyticendfeet.(B)Electronmicrographofboxedareain(A),showingtheappearanceoftightjunctionsbetweenneighboringendothelialcells(arrows).(AafterGoldstein,GoldsteinandBetz,1986;BfromPetersetal.,1991.)Anatomyoftheblood-brainbarrier第7頁，課件共15頁，創(chuàng)作于2023年2月第8頁，課件共15頁，創(chuàng)作于2023年2月Circumventricularorgans

Thecircumventricularorgansareregionsofthebrainwheretheblood-barrierbarrierisweak.Theseregionsallowssubstancestocrossintobraintissuemorefreelyandtherebyallowthebraintomonitorthemakeupoftheblood.

第9頁，課件共15頁，創(chuàng)作于2023年2月VariousfactorsandconditionscanleadtoaloweringoftheBBB.Theseinclude:Hypertension(highbloodpressure)Hyperosmolitity(ahighconcentrationofasubstanceintheblood)MicrowavesRadiationInfectionInjurytothebrainduetotrauma,ischemia,inflammation,orpressureAdditionally,theBBBisnotfullyformedatbirth.

Factorsthatcanlowertheblood-brainbarrier

第10頁，課件共15頁，創(chuàng)作于2023年2月Blood-brainborderandGlucoseTometabolizeglucoseinthebrain,ortoperformcerebralglucosemetabolism,requiresacomplex,multi-stepprocessinwhichthesugaristransportedintothebrain--breakingthewellwalledblood-brainborder,convertedtoanothersubstance,completesasetofchemicalreactions,andthenultimatelyoxidizedtocarbondioxideandwaterforthefulluseofitasenergy.

Blood-brainbarrier第11頁，課件共15頁，創(chuàng)作于2023年2月Blood-brainbarrierpermeabilityinthemousebrainMasakiUeno.ActaNeuropathol(2004)107:532–538第12頁，課件共15頁，創(chuàng)作于2023年2月Blood-brainbarrierpermeabilityintheratbrainFig.2A–FLightmicroscopicphotographsshowingthestainingforHRPwithTMBinWKY(AandD),SHR(BandE),andSHRSP(CandF).D,E,andFarehigher-powermagnificationsofthestainingforHRPwithTMBinthehippocampalareaindicatedbyarrowsinA,B,andC,respectively.NoHRPstainingisobservedinthehippocampusandcortexofWKY(AandD).ThestainingforHRPisseeninthehippocampus,especiallyaroundvessels(E,F:arrows)alongthehippocampalfissureofSHR(