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.,1,Braindysfunction,金静华DepartmentofNeurobiologyjhjin,.,2,Outline,I:GeneralconceptionabouthumanbrainII:CognitivedisorderIII:ConsciousnessdisorderIV:Summary,.,3,1.StructuralCharacteristics,Itislocatedinsidetheskull,protectsbrainfrominjury,confinesthebrainItiscomposedofneuronsandglialcellsThebloodsupplyisfromtwinvertebralarteriesandcarotisinterna(颈内动脉)Thebrainbloodbarrierprotectsbrainfrominvasionoftoxicinsults,.,4,HumanBrain,Tounderstandthedysfunctionofthebrain,itsimportanttoknowabitaboutthebrain,TheBrainsVitalStatisticsAdultweight:about3poundsAdultsize:amediumcauliflowerNumberofneurons:100billionNumberofsynapses:100trillion,.,5,InsidetheHumanBrain,.,6,CellTypesoftheBrain,NeuronsGlia,.,7,StructureofNeuron,.,8,Neurons,SpecializedRegionsofNeuronsCarryoutDifferentFunctions,Structureoftypicalmammalianneurons,Hippocampus(海马),.,9,Glia,.,10,CellularFunctions,NeuronisinchargeofdifferentfunctionsGlianourishesandprotectstheneurons,.,11,Howareneuronsconnected?,Synapses!,Spine,.,12,HowdoestheSynapsecarrythesignal?,1.ElectricalcurrenttravelsdowntheaxonVesicleswithchemicalsmovetowardthemembraneChemicalsarereleasedanddiffusetowardthenextcellsplasmamembrane4.Thechemicalsopenupthetransportproteinsandallowthesignaltopasstothenextcell,.,13,2.CharacteristicsofMetabolism,ThemostactiveorganinenergymetabolismGlucoseisalmosttheonlysourceofbrainenergyThestorageofglucoseinthebrainisverylimited,.,14,3.CharacteristicsofBrainDisease,Region-dependentconsequencestoinjuriesLimitedcapacityforselfrepairAcutebraindamageswillcausedisturbanceinconsciousnesswhereaschroniclesionsusuallyleadtocognitivedysfunction,.,15,BrainresponsestoInjuries,Cellularresponses:Neurondeath(necrosis,apoptosis)Degeneration(axon/dendritesretraction,atrophy)Inflammation(microglia,astrocytes)Demyelination(oligodentrocytes)Functionalresponses:CognitivedisorderConsciousnessdisorder,.,16,Outline,I:GeneralconceptionabouthumanbrainII:CognitivedisorderIII:ConsciousnessdisorderIV:Summary,.,17,1.Cognition,Theabilityofthebraintoprocessandstoreinformationinordertosolveproblems.Itinvolvesaseriesofvoluntarypsychologicalandsocialbehaviors,suchasstudy,memory,language,thinking,emotionetc.,.,18,StructuralBasisofCognition,BrodmannMapping(52areas),Cerebralcortex,.,19,Functionofcerebralcortex,Frontalcortex:voluntarymovements,complexintellectualactivitiessuchaswriting,memory,creativity,judgment,visionandsocialresponsibility.Lesionsinthisareawillresultincontralateralhemiplegia(偏瘫),agraphia(失写症)andfrontaldementia(痴呆).DamageinBrocasarea(44and45)resultinmotoraphasia(Brocasaphasia失语症),.,20,Functionofcerebralcortex,Parietalcortex:playsmajorroleinhighlevelprocessandintegrationofsensoryinformation.Lesionsinthisareaproducecontrolateralsensorydeficits.Lesionsintheangulargyrus(角回)resultinalexia(失读症).Lesionsinthesupamarginalgyrus(缘上回)resultinastereognosis(实体感觉缺失).,.,21,Functionofcerebralcortex,Temporalcortex:sensoryreceivingareaforauditoryimpluses.Lesionsinarea22(auditoryassociationcortex)canleadtoWernickesaphasia(感觉性失语)Lesionsintemporalhippocampuscanproducespatialoremotionalmemoryimpairment,.,22,Functionofcerebralcortex,Occipitalcortex:visionLesionsintheprimaryvisualcortexresultinvisualfieldsdefects.Lesionsinthevisualassociationcortexresultinalackofrecognitionofobjectsandindistinguishingthedifferenceofanimals(catvs.dog).,.,23,2.CognitiveDisorder,Thedisturbanceofthementalprocessrelatedtolearningandmemory,reasoningandjudgment,accompaniedbyaphasia(失语),apraxia(失用),agonasia(失认)ordisturbanceinexecutivefunctioning,.,24,MajorManifestations,LearningandmemorydisordersAphasiaAgonosiaApraxiaDementia,.,25,Learningandmemorydeficits:PatientHM:MRI,HMslesionincludesmedialtemporallopestructuresinadditiontohippocampus(amygdala,entorhinalcortex),.,26,HMsgoodnewsandbadnews,ThesurgeryhadaprofoundeffectondeclarativememorySevereanterogradeamnesiaMildretrogradeamnesiaDisabilitytotransfernewshort-termmemoryintolong-termmemoryButtherewasnoeffecton:PersonalityAttentionIntelligenceManyformsofmemorywerespared(short-termmemory,motor,implicitmemory,etc).,.,27,3.EtiologyandPathogenesis,ChronicbraindamageChronicsystemicdiseasesMentalandpsychicdisorderOtherfactors,.,28,ChronicBrainDamage,ImbalanceofregulatingmoleculesinthebrainProteinaggregationinthebrainChroniccerebralischemicinjuryEnvironmentalandmetabolictoxinsCerebraltraumaBrainaging,.,29,(1)ImbalanceofRegulatingMolecules,DopamineNorepinephrineAcetylcholine(Ach)GlutamateAberrantneuropeptideLackofneurotrophicfactors,.,30,DopaminePathway,Dopamine,.,31,DopamineSynthesisandStorageTyrosineL-DOPADA,.,32,Distribution:Dopaminepathway,.,33,ParkinsonDisease,.,34,Norepinephrine,.,35,Glutamate,.,36,(2)ProteinAggregationintheBrain,GenemutationsAbnormalpost-translationalmodificationInfectionofslowvirusinthebrain,.,37,CleavedtogenerateN-terminalpolyQfragmentsAggregatesformincytoplasmandinnucleus-amyloid-likeconformationControversyoverwhetheraggregatesaretoxicorprotectiveGainoftoxicfunctionand/orlossofprotectivefunction,Q,Q,Q,Q,Q,Q,Q,Q,Q,MutantHuntingtininHuntingtonsdisease,.,38,Mutanta-synucleininParkinsonsdisease,.,39,AlzheimerDisease,.,40,AlzheimersDisease,GradualmemorylossDeclineintheabilitytoperformroutinetasksDisorientationDifficultyinlearningLossoflanguageskillsImpairmentofjudgmentandplanningPersonalitychanges,.,41,Senileplaques,Neurofibrillarytangles,.,42,.,43,.,44,(3)ChronicCerebralIschemicInjury,EnergyexhaustionandacidosisIntracellularcalciumoverloadFreeradicalinjuryExcitatorytoxicityInflammatoryreactionbycytokine,.,45,Excitatorytoxicity,Ageneralpathologicprocessbeginningwiththeenergyandmetabolicdysfunctioncausedbycerebralischemiaandanoxia,whichthenresultininhibitionofNa+-K+-ATPaseinplasmamembrane,elevationofextracellularK+anddepolarizationofneurons.ThesechangesthencauseoverdosedreleaseofEAA(excitatoryaminoacids)intothesynapticcleftandoveracitvationofEAAreceptor,ultimatelyoverexcitementanddeathofneurons.,.,46,PathogenesisofCognitiveDisorder,.,47,4.PrinciplesforTreatmentofCognitiveDisorders,GeneralneuroprotectivetreatmentsMaintenanceofnormalneurotransmitterlevelSurgery,.,48,Outline,I:GeneralconceptionabouthumanbrainII:CognitivedisorderIII:ConsciousnessdisorderIV:Summary,.,49,1.Consciousness,Thesenseofawarenessofselfandtheenvironment.Itconsistsoftwoaspects:Stateofarousalandcontentofconsciousness.,.,50,2.ConsciousnessDisorder,Parenchymalmentaldisordersinwhichthereisimpairmentoftheabilitytomaintainawarenessofselfandenvironmentandtorespondtoenvironmentalstimuli.,.,51,StructuralBasisforConsciousness,.,52,StructuralBasisforConsciousnessdisorders,DysfunctionofbrainstemreticularformationDysfunctionofthalamusDysfunctionofcerebralcortex,.,53,MajorManifestations,Delirium,Confusion,Drowsiness,Coma,谵妄,精神错乱,昏睡,昏迷,.,54,3.EtiologyandPathogenesis,Acutebraininjuryeg.Diffuseencephalicinfection,diffusebraintrauma,subarachnoidhemorrhage,etc.AcutebrainintoxicationIntracranialextrusionanddestructivelesion,

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