简介：TheAmericanHeartAssociationandtheEuropeanResuscitationCouncilrecentlyrecommendedthatvasopressincanbeusedforcardiopulmonaryresuscitation,insteadofepinephrine.However,theguidelinesdonotdiscusstheeffectsofvasopressinduringcerebralresuscitation.Inthisstudy,weintraperitoneallyinjectedepinephrineand/orvasopressinduringcardiopulmonaryresuscitationinaratmodelofasphyxialcardiacarrest.Theresultsdemonstratedthat,comparedwithepinephrinealone,thepathologicaldamagetonervecellswaslessened,andthelevelsofc-JunN-terminalkinaseandp38expressionweresignificantlydecreasedinthehippocampusaftertreatmentwithvasopressinaloneorthevasopressinandepinephrinecombination.Nosignificantdifferenceinresuscitationeffectswasdetectedbetweenvasopressinaloneandthevasopressinandepinephrinecombination.Theseresultssuggestthatvasopressinaloneorthevasopressinandepinephrinecombinationsuppresstheactivationofmitogen-activatedproteinkinaseandc-JunN-terminalkinasesignalingpathwaysandreduceneuronalapoptosisduringcardiopulmonaryresuscitation.

简介：GinsenosideRg1（Rg1）hasanti-agingandanti-neurodegenerativeeffects.However,themechanismsunderlyingtheseactionsremainunclear.TheaimofthepresentstudywastodeterminewhetherRg1affectshippocampalsurvivalandneuriteoutgrowthinvitroafterexposuretoamyloid-betapeptidefragment25–35(Aβ25–35),andtoexplorewhethertheextracellularsignal-regulatedkinase（ERK）andAktsignalingpathwaysareinvolvedinthesebiologicalprocesses.Weculturedhippocampalneuronsfromnewbornratsfor24hours,thenaddedRg1tothemediumforanother24hours,withorwithoutpharmacologicalinhibitorsofthemitogen-activatedproteinkinase（MAPK）familyorAktsignalingpathwaysforafurther24hours.Wethenimmunostainedtheneuronsforgrowthassociatedprotein-43,andmeasuredneuritelength.Inaseparateexperiment,weexposedculturedhippocampalneuronstoAβ25–35for30minutes,beforeaddingRg1for48hours,withorwithoutAktorMAPKinhibitors,andassessedneuronalsurvivalusingHoechst33258staining,andphosphorylationofERK1/2andAktbywesternblotanalysis.Rg1inducedneuriteoutgrowth,andthiseffectwasblockedbyAPI-2（Aktinhibitor）andPD98059（MAPK/ERKkinaseinhibitor）,butnotbySP600125orSB203580（inhibitorsofc-JunN-terminalkinaseandp38MAPK,respectively）.Consistentwiththiseffect,Rg1upregulatedthephosphorylationofAktandERK1/2;theseeffectswerereversedbyAPI-2andPD98059,respectively.Inaddition,Rg1significantlyreversedAβ25–35-inducedapoptosis;thiseffectwasblockedbyAPI-2andPD98059,butnotbySP600125orSB203580.Finally,Rg1significantlyreversedtheAβ25–35-induceddecreaseinAktandERK1/2phosphorylation,butAPI-2preventedthisreversal.OurresultsindicatethatRg1enhancesneuriteoutgrowthandprotectsagainstAβ25–35-induceddamage,andthatitsmechanismmayinvolvetheactivationofAktandERK1/2signaling.更多还原

简介：BACKGROUND:GenetherapyforParkinson'sdiseaseisbeingexploredasaneffectivestrategytorestoreandprotectthefunctionofneuronalcellsinthesubstantianigra.Regulationofgeneexpressionisnecessaryforgenetherapytoavoidadverseeffectsduetoexcessivesynthesisoftransgeneproducts.OBJECTIVE:Herewedevelopedrecombinantadeno-associatedvirus(AAV)asaviralvector-mediatedgeneregulationsystembasedonCrerecombinasefusedtothemutatedligand-bindingdomainoftheestrogenreceptor(CreERT2)+inducingagenttamoxifen.InducibleCrerecombinasewasusedtoreducetyrosinehydroxylasegeneexpressionandtopreventtheexcessiveincreaseindopamine.DESIGN,TIMEANDSETTING:Ageneticengineeringinvitrocomparativestudyandrandomizedcontrolledanimalexperiment.ThisstudywasconductedattheGeneTherapyCenter,JichiMedicalSchool,JapanfromJune2002toJune2004.METHODS:ToconstructarecombinantAAVvectorcarryingadopaminesynthasegene.ThetyrosinehydroxylasegenewasinsertedusingaloxPfragmentthatcouldberegulatedbyCrerecombinase.TherecombinantAAVvectorcarryingtheCreERT2genewasco-transducedwithHEK293cellsandthecorpusstriatuminaratmodelofParkinson'sdisease,withinducingagenttamoxifentoregulategeneexpression.MAINOUTCOMEMEASURES:ThelevelsofdopamineandaromaticL-aminoaciddecarboxylase(AADC)activityweredetectedinHEK293cellmediumandinthecorpusstriatuminaratmodelofParkinson'sdiseaseusinghigh-performanceliquidchromatography.ImmunofluorescencedoublestainingwasusedtoobservetyrosinehydroxylaseandCreorAADCco-expressioninHEK293cellmedium.ImmunohistochemicalstainingwasemployedtoobservetyrosinehydroxylaseandAADCexpressionandbehavioralchangesweremeasuredinParkinson'srats.RESULTS:TransfectedAAV-CreERT2andAAVexpressingdopaminesynthesisenzymescouldincreasethesynthesisofdopamineinHEK293mediumandParkinson'sratstriatum(P<0.01)andimprovetherotationalbehaviorofParkin

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简介：BACKGROUND:Studieshavedemonstratedthatthemechanismsunderlyingcellularapoptosissignaltransductionfocusontwopathways:intracellularmitochondriaandextracellulardeathreceptor.Thecurrentevidencesupportsthatsignaltransductionofcellularapoptosisalsoincludesendoplasmicreticulumstresssignaltransduction.OBJECTIVE:ToobserveCaspase-12expressionandcellularapoptosisfollowingischemiainratswithprogressivespinalcordcompression,andtoverifytheinfluenceofendoplasmicreticulumstressontheapoptosisinducedbyspinalcordinjury.DESIGN,TIMEANDSETTING:Arandomized,controlled,animaltrialwasperformedattheInstituteofNeuroscienceinChongqingMedicalUniversitybetweenJanuaryandOctoberin2006.MATERIALS:Immunohistochemicalkit,diaminobenzidine,andTUNELkitwerepurchasedfromBeijingZhongshanBiotechnology,China;rabbitanti-ratCaspase-12monoclonalantibodywasprovidedbySantaCruz,USA.METHODS:SixtyWistarrats,aged3-4months,wererandomlyassignedtoamodelgroup(n=50),whichunderwentspinalcordcompressionintheL_1segmentfollowingL_1laminectomyandarticularprocessexcisiontoestablishamodelofprogressivespinalcordcompression,andasham-surgerygroup(n=10),whichunderwentonlylaminectomy.Startingwiththefirstdayaftersurgery,theratswerelocallyanesthetized,theskinwasopened,andthescrewwasrotatedby1/4ofacycle,twiceweekly.MAINOUTCOMEMEASURES:At3,7,14,21,and28daysaftersurgery,ratsfromeachgroupwereanesthetized,andthespinalcordswereresected.Pathologicalchangesfollowingspinalcordcompressionweredeterminedusinghematoxylin-eosinstaining,Nissldye,andtransmissionelectronmicroscopy.TheTUNELmethodwasusedtoobserveneuronalapoptosisinthecompressedspinalcordsegments.ImmunohistochemistryandWesternblotwereutilizedtodetectCaspase-12expressioninthecompressedsegments.RESULTS:Cellularswelling,neuraldegeneration,andalteredendoplasmicreticulumstructureswereobservedat3days

简介：Toobservetheeffectsofdifferentacupuncturemanipulationsonbloodpressureandtargetorgandamageinspontaneouslyhypertensiverats(SHRs),thisstudyusedthereinforcingtwirlingmethod(1.5–2-mmdepth;rotatingneedleclockwisefor360°andthencounterclockwisefor360°,withthethumbmovingheavilyforwardandgentlybackward,60timesperminutefor1minute,andretainingneedlefor9minutes),thereducingtwirlingmethod(1.5–2-mmdepth;rotatingneedlecounterclockwisefor360°andthenclockwisefor360°,withthethumbmovingheavilybackwardandgentlyforward,60timesperminutefor1minute,andretainingneedlefor9minutes),andtheneedleretainingmethod(1.5–2-mmdepthandretainingtheneedlefor10minutes).BilateralTaichong(LR3)wastreatedbyacupunctureusingdifferentmanipulationsandmanualstimulation.Reinforcingtwirling,reducingtwirling,andneedleretainingresultedinadecreasednumberofapoptoticcells,reducedBaxmRNAandproteinexpression,andanincreasedBcl-2/BaxratiointhehippocampuscomparedwiththeSHRgroup.Amongthesegroups,theBcl-2/Baxproteinratiowashighestinthereducingtwirlinggroup,andtheBcl-2/BaxmRNAratiowashighestintheneedleretaininggroup.Theseresultssuggestthatreinforcingtwirling,reducingtwirling,andneedleretainingmethodsallimprovebloodpressureandpreventtargetorgandamagebyincreasingthehippocampalBcl-2/BaxratioandinhibitingcellapoptosisinthehippocampusinSHR.

简介：Hypoxia-induciblefactor1(HIF-1)attenuatesamyloid-betaproteinneurotoxicityanddecreasesapoptosisinducedbyoxidativestressorhypoxiaincorticalneurons.Inthisstudy,weconstructedarecombinantadeno-associatedvirus(rAAV)vectorexpressingthehumanHIF-1αgene(rAAV-HIF-1α),andtestedtheassumptionthatrAAV-HIF-1αrepresseshippocampalneuronalapoptosisinducedbyamyloid-betaprotein.OurresultsconfirmedthatrAAV-HIF-1αsignificantlyreducesapoptosisinducedbyamyloid-betaproteininprimaryculturedhippocampalneurons.DirectintracerebralrAAV-HIF-1αadministrationalsoinducedrobustandprolongedHIF-1αproductioninrathippocampus.SinglerAAV-HIF-1αadministrationresultedindecreasedapoptosisofhippocampalneuronsinanAlzheimer’sdiseaseratmodelestablishedbyintracerebroventricularinjectionofaggregatedamyloid-betaprotein(25–35).OurinvitroandinvivofindingsdemonstratethatHIF-1haspotentialforattenuatinghippocampalneuronalapoptosisinducedbyamyloid-betaprotein,andprovidesexperimentalsupportfortreatmentofneurodegenerativediseasesusinggenetherapy.

简介：Forthetreatmentofbrainischemiausingacupuncture,theneedleispredominantlyinsertedintomuscularlayersanddeeptissue.However,fewstudieshaveinvestigatedtheoutcomesofshallowneedling.Thepresentstudyestablishedmiddlecerebralarteryocclusionmodelsinratsusingthethrombosismethod.ShallowneedlingandconventionalneedlingatthebilateralNeiguan(PC6)andGongsun(SP4)acupointsimprovedneurologicalfunctionofmiddlecerebralarteryocclusionrats,increasedtheexpressionoftheanti-apoptoticBcl-2,inhibitedtheexpressionofthepro-apoptoticBax,andreducedtheexpressionofthevasoactivesubstancesnitricoxidesynthaseandendothelin-1.However,thesechangesweremorepronouncedintheshallowneedlinggroup,indicatingthatshallowneedlingismoreeffectiveininhibitingbrainischemicinjury.

简介：Mitochondriaplayanimportantroleinneuronalapoptosiscausedbycerebralischemia,andtheroleismediatedbytheexpressionofmitochondrialproteins.Thisstudyinvestigatedtheinvolvementofmitochondrialproteinsinhippocampalcellapoptosisaftertransientcerebralischemia-reperfusioninjuryinagedratsusingacomparativeproteomicsstrategy.Ourexperimentalresultsshowthattheagedratbrainissensitivetoischemia-reperfusioninjuryandthattransientischemialedtocellapoptosisinthehippocampusandchangesinmemoryandcognitionofagedrats.Differentialproteomicsanalysissuggestedthatthisphenomenonmaybemediatedbymitochondrialproteinsassociatedwithenergymetabolismandapoptosisinagedrats.Thisstudyprovidespotentialdrugtargetsforthetreatmentoftransientcerebralischemia-reperfusioninjury.