简介：BACKGROUND:Ithasbeensuggestedthatmelatonin(MT)canprotectsecondaryneuronalinjury.However,theprotectiveeffectofMTonneuronalinjuryinischemia/reperfusionmodelsinvitrostillhasnotbeenproved.OBJECTIVE:ToinvestigatetheprotectiveeffectofMToncentralischemicinjuryofnervecellsandanalyzeitspossiblemechanism.DESIGN:Contrastobservationalstudy.SETTING:DepartmentofBiochemistryandMolecularBiology,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology.MATERIALS:Ratsaged7-8daysandweighing10-12gwereprovidedbyMedicalExperimentalAnimalCenter,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,MTwasprovidedbySigmaCompany,USA.METHODS:TheexperimentwascarriedoutintheLaboratoryofBiochemistryandMolecularBiology,TongjiHospital,HuazhongUniversityofScienceandTechnologyfromOctober2002toMarch2004.TheeffectsofMTontheneurodegenerationinducedbyoxygen-glucose-deprivation(OGD)weretestedinculturedratcerebellargranulecells.NeurondamagewasquantitativelyassessedbyTypanBlueexclusionandMTTassayatdifferenttimepointsafteroxygen-glucose-deprivation(90minutes).DNAgelelectrophoresisandacridineorangestainwereperformedtodeterminethenatureofcelldamage.Andfluorescencespectrophotometerwasusedforquantificationofintracellularmalondialdehyde(MDA)atvarioustimeintervals.MAINOUTCOMEMEASURES:Correlationbetweendegreesofneuronalinjuryandreperfusiontimes,apoptosis,andproductionofMDAincells.RESULTS:①Theneuroninjurywasaggravatedwithreperfusiontime.②TheprotectiveeffectofMTwastime-anddose-dependentwhenitsconcentrationwasnothigherthan10μmol/L.⑧WhenneuronswereexposedtoOGDfor90minutes.partofthecellsexhibitedtypicalfeaturesofapoptosis:internucleosomalDNAcondensationandDNAladderonagarosegelelectrophoresis.MTaddedtocellsrecoveringfromOGDexertedneuroprotectiveactionagainstOGD-inducedapoptosis.④InOGDexposedculture

简介：Brainischemicstrokeistheleadingcauseoflong-lastinginjury,disability,anddeathinadults.Althoughthebrainrepresentsonlyabout2%ofthetotalbodymass,itconsumesalmost20%ofthebody’soxygen.Asaresult,braincellsareextremelysensitivetohypoxia.Oncecerebralischemiaoccurs,thecoreofthe

简介：Oxidativestressiscloselyassociatedwithsecondarycelldeathinmanydisordersofthecentralnervoussystemincludingstroke,Parkinson’sdisease,Alzheimer’sdisease.Amongmanyaberrantoxidativestress-associatedproteins,DJ-1hasbeenassociatedwiththeoxidativestresscelldeathcascadeprimarilyinParkinson’sdisease.Althoughprincipallyexpressedinthecytoplasmandnucleus,DJ-1canbesecretedintotheserumunderpathologicalcondition.Recently,aclosepathologicalassociationbetweenDJ-1andoxidativestressinstrokehasbeenimplicated.Tothisend,weandothershavedemonstratedtheimportantroleofmitochondriainneuroprotectionforstrokebydemonstratingthatthetranslocationofDJ-1inthemitochondriacouldpotentiallymitigatemitochondrialinjury.Here,wediscussourrecentfindingstestingthehypothesisthatDJ-1notonlyfunctionsasaformofintracellularprotectionfromoxidativestress,butthatitalsoutilizesparacrineand/orautocrinecuesinordertoaccomplishextracellularsignalingbetweenneighboringneuronalcells,resultinginneuroprotection.ThisarticlehighlightsrecentevidencesupportingthestatusofDJ-1askeyanti-oxidativestresstherapeutictargetforstroke.

简介：Centralnervoussystem(CNS)injuriescausedbycerebrovascularpathologies(e.g.,stroke)ormechanicalcontusions(e.g.,traumaticbraininjury)disrupttheblood-brainbarrier(BBB)thatprotectstheCNSmicroenvironmentfromadirectcontactwithbloodsubstancesandcells.Theinitialneuraldamagecausedbythetraumaandtheischemicprocess

简介：Inflammationafterstrokeisthemaincauseofcerebralischemia/reperfusioninjury.Cascadingeventsafterinjurycanleadtocelldeath.Heatshockprotein70andotherendogenousinjury-signalingmoleculesarereleasedbydamagedcells,whichcanleadtosystemicstressreactions.Protectingthebrainthroughrepairbeginswiththestress-injury-repairsignalingchain.Thisstudyaimedtoverifywhetheracupunctureactsthroughthischaintofacilitateeffectivetreatmentofischemicstroke.Ratmodelsofcerebralischemia/reperfusioninjurywereestablishedbyZeaLonga'smethod,andinjurysiteswereidentifiedbyassessingneurologicalfunction,2,3,5-triphenyltetrazoliumchloridestaining,andhematoxylin-eosinstaining.ElectroacupunctureatacupointsBaihui(DU20)andZusanli(ST36)wasperformedinthemodelratswithdilatationalwaves,deliveredfor20minutesadayat2–100Hzandanamplitudeof2mA.Weanalyzedthebloodserumfromtheratsandfoundthatinflammatorycytokinesaffectedthelevelsofadrenotrophinandheatshockprotein70,eachofwhichfollowedasimilarbimodalcurve.Specifically,electroacupunctureloweredthepeaklevelsofadrenocorticotrophichormoneandheatshockprotein70.Thus,electroacupuncturewasabletoinhibitexcessivestress,reduceinflammation,andpromotetherepairofneurons,whichfacilitatedhealingofischemicstroke.

简介：Freeradicalsinducedbytraumaticbraininjuryhavedeleteriouseffectsonthefunctionandantioxidantvitaminlevelsofseveralorgansystemsincludingthebrain.Melatoninpossessesantioxidanteffectonthebrainbymaintainingantioxidantenzymeandvitaminlevels.Weinvestigatedtheeffectsofmelatoninonantioxidantabilityinthecerebralcortexandbloodoftraumaticbraininjuryrats.Resultsshowedthatthecerebralcortexβ-carotene,vitaminC,vitaminE,reducedglutathione,anderythrocytereducedglutathionelevels,andplasmavitaminClevelweredecreasedbytraumaticbraininjurywhereastheywereincreasedfollowingmelatonintreatment.Inconclusion,melatoninseemstohaveprotectiveeffectsontraumaticbraininjury-inducedcerebralcortexandbloodtoxicitybyinhibitingfreeradicalformationandsupportingantioxidantvitaminredoxsystem.

简介：ActivinA,amemberofthetransforminggrowthfactor-betasuperfamily,playsaneuroprotectiveroleinmultipleneurologicaldiseases.Endoplasmicreticulum(ER)stress-mediatedapoptoticandautophagiccelldeathisimplicatedinawiderangeofdiseases,includingcerebralischemiaandneurodegenerativediseases.ThapsigarginwasusedtoinducePC12celldeath,andActivinAwasusedforintervention.OurresultsshowedthatActivinAsignificantlyinhibitedmorphologicalchangesinthapsigargin-inducedapoptoticcells,andtheexpressionofapoptosis-associatedproteins[cleaved-caspase-12,C/EBPhomologousprotein(CHOP)andcleaved-caspase-3]andbiomarkersofautophagy(Beclin-1andlightchain3),anddownregulatedtheexpressionofthapsigargin-inducedERstress-associatedproteins[inositolrequiringenzyme-1(IRE1),tumornecrosisfactorreceptor-associatedfactor2(TRAF2),apoptosissignal-regulatingkinase1(ASK1),c-JunN-terminalkinase(JNK)andp38].Theinhibitionofthapsigargin-inducedcelldeathwasconcentration-dependent.ThesefindingssuggestthatadministrationofActivinAprotectsPC12cellsagainstERstress-mediatedapoptoticandautophagiccelldeathbyinhibitingtheactivationoftheIRE1-TRAF2-ASK1-JNK/p38cascade.

简介：BACKGROUND:Mailuoning,aChineseherb,hasbeenwidelyusedinChinatotreatacuteischemicstroke,andthemajorcomponentexhibitsanti-oxidativeeffects.However,thepreciseanti-oxidationpathwayremainsuncertain.OBJECTIVE:TovalidatetheprotectiveeffectsofMailuoningonH2O2-inducedprimarycorticalneuroninjuryinembryonicmice.DESIGN,TIMEANDSETTING:ComparativeobservationandinvitroexperimentswereperformedattheJiangsuKeyLaboratoryforMolecularMedicinefromJanuary2008toSeptember2009.MATERIALS:Mailuoning(NanjingJinlingMedicalCompany,China),reactiveoxygenspecies(ROS)kit(BeyotimeBiotechnology,China),superoxidedismutase(SOD),Cu/ZnSODkit,malondialdehyde(MDA)kits(NanjingJiancheng,China),mitochondrialmembranepotential(GMS10013.1,GENMED,USA)andcatalaseactivityassaykit(BeyotimeBiotechnology,China)wereutilizedforthepresentstudy.METHODS:MouseembryoniccorticalneuronswereisolatedandculturedwithculturemediumcontainingH2O2(80μmol/L)and/orMailuoning(1.25μg/mL)for24hours.MAINOUTCOMEMEASURES:Neuronalviabilityanddeathweredetectedbymethylthiazolyltetrazdiumandflowcytometry;ROSproductionwasdeterminedbyflowcytometry;mitochondrialmembranepotentialwasdetectedusingfluorescentstaining;SODactivitywasdetectedusingamodifiednitrobluetetrazoliummethod;Cu/ZnSODandcatalaseactivitywasdetectedbyspectrophotometry;andMDAwasdeterminedusingthelipidperoxidationmethod.RESULTS:H2O2increasedROSproductionandMDAconcentration(P<0.05),anddecreasedmitochondrialmembranepotential,SOD,Cu/ZnSODandcatalaseactivity(P<0.05);thenumberofsurvivingneurons(P<0.05)wasalsoreduced.Mailuoningreversedthesechanges.CONCLUSION:MailuoningprotectsH2O2-inducedinjuryincorticalcellsbyinhibitingROSandMDA,increasingdepolarizationofmitochondrialmembrane,andenhancingSODandcatalaseactivity.

简介：1-methyl-4-phenylpyridiniumion(MPP+)inducesendoplasmicreticulumstressandactivatescaspase-12inPC12cells,leadingtoneuronalapoptosis.However,theunderlyingmolecularmechanismremainsunknown.Thepresentstudyinvestigatedtheregulatoryeffectsofnervegrowthfactor(Aktactivator)andlithiumchloride(glycogensynthasekinase-3βinhibitor)ontheendoplasmicreticulumstresssignalingpathway.TheresultsrevealedthatMPP+inducedexpressionofBipandC/EBPhomologousprotein.TheupregulationofBipandC/EBPhomologousprotein,aswellasthedecreasedpro-caspase-12levelinducedbyMPP+wereinhibitedbypretreatmentofthenervegrowthfactororlithiumchloride.Theseresultssuggestthatthephosphatidylinositol3kinase-Akt-glycogensynthasekinase-3βpathwayisinvolvedinMPP+-inducedendoplasmicreticulumstress.