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blood-brainbarrier(BBB)HuafuQ:279486524KeyfunctionsoftheBBBDiscoveryoftheblood-brainbarrierAnatomyoftheblood-brainbarrierCircumventricularorgansFactorsthatcanlowertheblood-brainbarrierBlood-brainborderandGlucoseBlood-brainbarrierpermeabilityinthemousebrainOutlineKeyfunctionsoftheBBBAmechanismthatcontrolsthepassageofsubstancesfromthebloodintothecerobrospinalfluidandthusintothebrainandspinalcord.Theblood-brainbarrier(BBB)letsessentialmetabolites,suchasoxygenandglucose,passfromthebloodtothebrainandcentralnervoussystem(CNS)butblocksmostmoleculesthataremoremassivethanabout500daltons.ThisisalowmassinbiomoleculartermsandmeansthateverythingfromhormonesandneurotransmitterstovirusesandbacteriaarerefusedaccesstothebrainbytheBBB.Italsomeansthatmanydrugs,whichwouldotherwisebecapableoftreatingdisordersoftheCNS,aredeniedaccesstotheveryregionswheretheywouldbeaffective.KeyfunctionsoftheBBBare:Protectingthebrainfrom"foreignsubstances"(suchasvirusesandbacteria)inthebloodthatcouldinjurethebrainShieldingthebrainfromhormonesandneurotransmittersintherestofthebodyMaintainingaconstantenvironment(homeostasis)forthebrainDiscoveryoftheblood-brainbarrierThespecialpropertiesoftheblood-brainbarrierwerefirstobservedinthelate19thcenturybytheGermanbacteriologistPaulEhrlich.Hefoundthatwhenheinjectedcoloreddyesintothebloodstreamtheyleakedoutofcapillariesinmostregionsofthebodytostainthesurroundingtissues;thebrain,however,remainedunstained.Ehrlichwronglysurmisedthatthebrainhadalowaffinityforthedyes.Itwashisstudent,EdwinGoldman,whodidtheotherhalfoftheexperimentandrealizedthetruthofwhatwasgoingon.Goldmaninjectedadyeintothecerebrospinalfluidthatsurroundsthebrainandobservedthatitstainedthebrain,butnothingelse.Goldmanncorrectlyconcludedthatthedyewasunabletocrossthespecializedwallsofbraincapillaries.Anatomyoftheblood-brainbarrierDiagramoftheblood-brainbarriertransversetoacapillary(A)Diagramofabraincapillaryincrosssectionandreconstructedviews,showingendothelialtightjunctionsandtheinvestmentofthecapillarybyastrocyticendfeet.(B)Electronmicrographofboxedareain(A),showingtheappearanceoftightjunctionsbetweenneighboringendothelialcells(arrows).(AafterGoldstein,GoldsteinandBetz,1986;BfromPetersetal.,1991.)Anatomyoftheblood-brainbarrierCircumventricularorgansThecircumventricularorgansareregionsofthebrainwheretheblood-barrierbarrierisweak.Theseregionsallowssubstancestocrossintobraintissuemorefreelyandtherebyallowthebraintomonitorthemakeupoftheblood.VariousfactorsandconditionscanleadtoaloweringoftheBBB.Theseinclude:Hypertension(highbloodpressure)Hyperosmolitity(ahighconcentrationofasubstanceintheblood)MicrowavesRadiationInfectionInjurytothebrainduetotrauma,ischemia,inflammation,orpressureAdditionally,theBBBisnotfullyformedatbirth.Factorsthatcanlowertheblood-brainbarrierBlood-brainborderandGlucoseTometabolizeglucoseinthebrain,ortoperformcerebralglucosemetabolism,requiresacomplex,multi-stepprocessinwhichthesugaristransportedintothebrain--breakingthewellwalledblood-brainborder,convertedtoanothersubstance,completesasetofchemicalreactions,andthenultimatelyoxidizedtocarbondioxideandwaterforthefulluseofitasenergy.Blood-brainbarrierBlood-brainbarrierpermeabilityinthemousebrainMasakiUeno.ActaNeuropathol(2004)107:532–538Blood-brainbarrierpermeabilityintheratbrainFig.2A–FLightmicroscopicphotographsshowingthestainingforHRPwithTMBinWKY(AandD),SHR(BandE),andSHRSP(CandF).D,E,andFarehigher-powermagnificationsofthestainingforHRPwithTMBinthehippocampalareaindicatedbyarrowsinA,B,andC,respectively.NoHRPstainingisobservedinthehippocampusandcortexofWKY(AandD).ThestainingforHRPisseeninthehippocampus,especiallyaroundvessels(E,F:arrows)alongthehippocampalfissureofSHR(BandE)andSHRSP(CandF).Scalebarsindicate1mmMasakiUeno.ActaNeuropathol(2004)107:532–538Nicolas.AmericanJournalofHypertension,2010Thankalot!