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简介：Axonaldegenerationisapivotalfeatureofmanyneurodegenerativeconditionsandsubstantiallyaccountsforneurologicalmorbidity.AwidelyusedexperimentalmodeltostudythemechanismsofaxonaldegenerationisWalleriandegeneration(WD),whichoccursafteracuteaxonalinjury.Intheperipheralnervoussystem(PNS),WDischaracterizedbyswiftdismantlingandclearanceofinjuredaxonswiththeirmyelinsheaths.Thisisaprerequisiteforsuccessfulaxonalregeneration.Inthecentralnervoussystem(CNS),WDismuchslower,whichsignificantlycontributestofailedaxonalregeneration.Althoughitiswell-documentedthatSchwanncells(SCs)haveacriticalroleintheregenerativepotentialofthePNS,todatewehaveonlyscarceknowledgeastohowSCs‘sense'axonalinjuryandimmediatelyrespondtoit.Inthisregard,itremainsunknownastowhetherSCsplaytheroleofapassivebystanderoranactivedirectorduringtheexecutionofthehighlyorchestrateddisintegrationprogramofaxons.Olderreports,togetherwithmorerecentstudies,suggestthatSCsmountdynamicinjuryresponsesminutesafteraxonalinjury,longbeforeaxonalbreakdownoccurs.TheswiftSCresponsetoaxonalinjurycouldplayeitherapro-degenerativerole,oralternativelyasupportiverole,totheintegrityofdistressedaxonsthathavenotyetcommittedtodegenerate.Indeed,supportingthelatterconcept,recentfindingsinachronicPNSneurodegenerationmodelindicatethatdeactivationofakeymoleculepromotingSCinjuryresponsesexacerbatesaxonalloss.Ifthisholdstrueinabroaderspectrumofconditions,itmayprovidethegroundsforthedevelopmentofnewglia-centrictherapeuticapproachestocounteractaxonalloss.

简介：Stemcellshavetheremarkablepotentialtodevelopintomanydifferentcelltypes,essentiallywithoutlimittoreplenishothercellsaslongasthepersonoranimalisstillalive,offeringimmensehopeofcuringAlzheimer’sdisease,repairingdamagedspinalcords,treatingkidney,liverandlungdiseasesandmakingdamagedheartswhole.Untilrecently,scientistsprimarilyworkedwithtwokindsofstemcellsfromanimalsandhumans:embryonicstemcellsandnon-embryonic'somatic'or'adult'stemcells.Recentbreakthroughmakeitpossibletoconvertor'reprogram'specializedadultcellstoassumeastemstem-likecellswithdifferenttechnologies.Thereviewwillbrieflydiscusstherecentprogressesinthisarea.更多还原

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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.

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简介：Peripheralnerveinjuries(PNI)areamajorclinicalproblem.Ingeneral,PNIresultsfrommotorvehicleaccidents,lacerationswithsharpobjects,penetratingtrauma(gunshotwounds)andstretchingorcrushingtraumaandfractures.ItisestimatedthatPNIoccurin2.8%oftraumapatientsandthisnumberreaches5%ifplexusandrootlesionsarein-

简介：OBJECTIVE:Theaimofthisstudywastoevaluatetheeffectivenessandsafetyofstemcelltransplantationforspinalcordinjury(SCI).DATASOURCES:PubMed,EMBASE,Cochrane,ChinaNationalKnowledgeInfrastructure,ChinaScienceandTechnologyJournal,Wanfang,andSinoMeddatabasesweresystematicallysearchedbycomputertoselectclinicalrandomizedcontrolledtrialsusingstemcelltransplantationtotreatSCI,publishedbetweeneachdatabaseinitiationandJuly2016.DATASELECTION:RandomizedcontrolledtrialscomparingstemcelltransplantationwithrehabilitationtreatmentforpatientswithSCI.Inclusioncriteria:(1)PatientswithSCIdiagnosedaccordingtotheAmericanSpinalInjuryAssociation(ASIA)InternationalstandardsforneurologicalclassificationofSCI;(2)patientswithSCIwhoreceivedonlystemcelltransplantationtherapyorstemcelltransplantationcombinedwithrehabilitationtherapy;(3)oneormoreofthefollowingoutcomesreported:outcomesconcerningneurologicalfunctionincludingsensoryfunctionandlocomotorfunction,activitiesofdailyliving,urinationfunctions,andseverityofSCIoradverseeffects.Studiescomprisingpatientswithcomplications,withoutfull-text,andpreclinicalanimalmodelswereexcluded.QualityoftheincludedstudieswasevaluatedusingtheCochraneriskofbiasassessmenttoolandRevManV5.3software,providedbytheCochraneCollaboration,wasusedtoperformstatisticalanalysis.OUTCOMEMEASURES:ASIAmotorscore,ASIAlighttouchscore,ASIApinprickscore,ASIAimpairmentscalegradingimprovementrate,activitiesofdailylivingscore,residualurinevolume,andadverseevents.RESULTS:Tenstudiescomprising377patientswereincludedintheanalysisandtheoverallriskofbiaswasrelativelylowlevel.Fourstudiesdidnotdetailhowrandomsequencesweregenerated,twostudiesdidnotclearlystatetheblindingoutcomeassessment,twostudieslackedblindingoutcomeassessment,onestudylackedfollow-upinformation,andfourstudiesc

简介：Recentstudieshaveshownthattheglycation-associateddamageisnotlimitedtopatientswithdiabetes.Becauseoftheirassociationwithoxidativestress,advancedglycationend-products(AGEs)havealsobeenimplicatedinmanyneurodegenerativediseases,suchasHuntingtondisease,amyotrophiclateralsclerosis,andAlzheimerdisease(Yanetal.,

简介：Forty-threepatientswithchronicspinalcordinjuryforover6monthsweretransplantedwithembryonicolfactoryensheathingcells,2–4×106,intomultiplesitesintheinjuredareaunderthesurgicalmicroscope.Thesympatheticskinresponseinpatientswasmeasuredwithanelectromyography/evokedpotentialinstrument1daybeforetransplantationand3–8weeksaftertransplantation.SpinalnervefunctionofpatientswasassessedusingtheAmericanSpinalInjuryAssociationimpairmentscale.Thesympatheticskinresponsewaselicitedin32casesbeforeolfactoryensheathingcelltransplantation,whileitwasobservedin34casesaftertransplantation.Concomitantly,sympatheticskinresponselatencydecreasedsignificantlyandamplitudeincreasedsignificantlyaftertransplantation.TransplantationofolfactoryensheathingcellsalsoimprovedAmericanSpinalInjuryAssociationscoresformovement,painandlighttouch.Ourfindingsindicatethatolfactoryensheathingcelltransplantationimprovesmotor,sensoryandautonomicnervefunctionsinpatientswithchronicspinalcordinjury.

简介：cAMPsignalingandthecontrolofSchwanncellfate:Theubiquitoussecondmessengercyclicadenosinemonophosphate(cAMP)controlsavarietyofcellularresponsesinacelltype-specificandstimulus-dependentmannerthroughanelaboratenetworkofsignalingintermediariesthatconnectstimulationofcellmembranereceptors(typicallyG

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简介：Alzheimer’sdisease(AD)isoneofthemostdevastatingdiseasesaffectingthelifeandhealthofagingpopulation.TwohallmarksofADaresenileplaquesandneurofibrillarytangles,andADiswellknownforthemassivelossofneuronsandimpairedcognitivefunctionsespeciallymemoryloss.Despiteextensivesearchforeffectivetreatment,available

简介：Thecentralnervoussystem(CNS)containsthetwomostimportantorgans,thebrainandspinalcord,fortheorchestrationofthementalandphysicalactivitiesoflife.Becauseofitsimportance,thehumanbodyhasevolvedbarriersystemstoprotectCNStissuefromtheexternalenvironment.Thisbarrierisamembranecomposedoftightlyapposedcellsandisselectivelypermeabletospecificmoleculesbywayofmembranetransporters.Themajorbarriersinthebrainandtheircorrespondingcellularconstituentsarethebloodbrainbarrier(BBB)composedofendothelialcellsinbrain

简介：BACKGROUND:Olfactoryensheathingcelltransplantationcanactivateaxonalregenerationandenhancemyelinrepair,whicharebeneficialfortreatingdemyelinatingdiseases.OBJECTIVE:Toexploretheeffectsofolfactoryensheathingcelltransplantationonmyelinrepair,synaptophysinexpression,andmotorfunctioninaratmodelofexperimentalallergicencephalomyelitis.DESIGN,TIMEANDSETTING:Arandomized,controlledexperimentwasperformedattheLaboratoryofProvincialHospitalaffiliatedtoShandongUniversitybetweenAugust2006andSeptember2007.MATERIALS:Dibenzylamine(Hoechst33342),luxolfastblue,andrabbitanti-ratsynaptophysinantibodywereprovidedbySigma,USA.METHODS:OlfactoryensheathingcellsextractedfromneonatalWistarratswereculturedfor10-14daysandlabeledwithdibenzylamine.SpinalcordextractedfromahealthyguineapigwashomogenizedandequallymixedwithcompleteFreund'sadjuvant;thereafter,themixturewasintracutaneouslyinjectedintotwoposteriorvoixpedisofhealthymaleWistarratstoestablishmodelsofexperimentalallergicencephalomyelitis.Ratswererandomlydividedintoacontrolencephalomyelitisgroupandanolfactoryensheathingcelltransplantationgroup,36ratsineachgroup.Physiologicalsaline(2μL)oranolfactoryensheathingcellsuspension(2μL)wasseparatelyinjectedalonglateralcerebralventricleatday7post-modelinduction.MAINOUTCOMEMEASURES:Themigrationanddistributionofolfactoryensheathingcellswereobservedunderfluorescencemicroscopy;myelinrepairwasdetectedusinghematoxylin-eosinstainingandluxolfastbluestaining;synaptophysinexpressionwasmeasuredusingimmunohistochemicalstaining;motorfunctionwasevaluatedusingamotorfunctionscale.RESULTS:Olfactoryensheathingcellscouldsurviveinvivoandmigratetothedistalendofthetransplantfocusandspinalcord,andsurvived21days.Hematoxylin-eosinstainingandluxolfastbluestainingindicatedthatmyelininthetransplantationgroupwasintact,andtheinfla

简介：Tourette'ssyndromeistreatedbybehavioralorpharmacologicaltherapy.However,patientswithmalignantTourette'ssyndromealsoexhibitlife-threateningsymptoms,whichareunresponsivetoconservativetreatmentsorneurosurgicalprocedures,suchasdeepbrainstimulation.Inrecentyears,mesenchymalstemcells(MSCs)haveshowntherapeuticpotentialinmanyneurologicaldiseases.Therefore,thepresentstudyproposedtouseMSCtransplantationasanoveltherapyforTourette'ssyndrome.StereotypicbehaviorsinTourette'ssyndromeratsdecreasedsignificantlyat21daysafterhumanMSCstransplantationintothestriatum.ImmunohistochemistryanalysesrevealedsurvivaloftransplantedhumanMSCsanddifferentiationintoneuronsandastrocytesintheratbrain.ResultssuggestthatintrastriataltransplantationofhumanMSCscouldprovidetherapeuticpotentialforTourette'ssyndrome.

简介：BACKGROUND:Microgliaareverysensitivetoenvironmentalchanges,oftenbecomingactivatedbypathologicalconditions.Activatedmicrogliacanexertadualroleininjuryandrepairinvariousdiseasesofthecentralnervoussystem,includingcerebralischemia,Parkinson’sdisease,andAlzheimer’sdisease.OBJECTIVE:Animmortalmicroglialcellline,BV2,wastreatedwithvaryingconcentrationsoflipopolysaccharide(LPS)toinduceapathologicalsituation.Supernatantwasharvestedandincubatedwithbonemarrowmesenchymalstemcellsand,concomitantly,bonemarrowmesenchymalstemcelldifferentiationwasobserved.DESIGN:Acontrolledobservation,invitroexperiment.SETTING:DepartmentofNeurology,FirstAffiliatedHospitalofChinaMedicalUniversity.MATERIALS:Fivemale2–3-week-oldSpragueDawleyratswerepurchasedfromAnimalLaboratoryCenterofChinaMedicalUniversityandincludedinthisstudy.Theprotocolwasperformedinaccordancewithethicalguidelinesfortheuseandcareofanimals.ThemicroglialcelllineBV2wasproducedbyCellResearchInstituteofChineseAcademyofSciences.LPSwasproducedbySigmaCompany,USA.METHODS:ThisstudywasperformedintheCentralLaboratoryofChinaMedicalUniversityfromSeptember2006toMarch2007.Ratfemoralandtibialbonemarrowwascollectedforseparationandprimarycultureofbonemarrowmesenchymalstemcells.Bonemarrowmesenchymalstemcellculturesweredividedinto5groups:controlgroup,non-activatedgroup,aswellaslow-,medium-,andhigh-doseLPSgroups.Inthecontrolgroup,bonemarrowmesenchymalstemcellswereculturedwithDulbecco’smodifiedEagle’smedium(DMEM)supplementedwithfetalbovineserum(volumefraction0.1).Inthenon-activatedgroup,bonemarrowmesenchymalstemcellswereincubatedwithnon-activatedBV2supernatant.Inthelow-,medium-,andhigh-doseLPSgroups,bonemarrowmesenchymalstemcellswereincubatedwithLPS(0.01,0.1and1μg/L,respectively)-activatedBV2supernatant.MAIN

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:Animalexperimentshaveconfirmedthatbonemarrowstromalcell(BMSC)transplantationcanserveasatreatmentforepilepsy.OBJECTIVE:BMSCsderivedfromgreenfluorescentprotein(GFP)miceweretransplantedintothehippocampalCA1regionofepilepticrats.Theaimofthestudywastorecordelectroencephalogram(EEG),analyzesurvivalandmigrationofBMSCs,andvalidatetheeffectofBMSCtransplantationforthetreatmentofepilepsy.DESIGN,TIMEANDSETTING:ArandomizedblockdesignexperimentwasperformedattheInstituteofNeuroscience,KunmingMedicalCollegefromMarch2005toFebruary2006.MATERIALS:HomozygousC57BL/6CrSlcTgN(acr-EGFP)OsbC14-Y01-FM131mice,8-12weeksofage,wereselectedforpreparationofcellsuspension.SpragueDawleyratswereselectedforestablishingepilepsymodels.METHODS:Ratswererandomlydividedinto4groups:control(n=8),model(n=8),normalsaline(n=24),andBMSC(n=24).Inthemodel,normalsaline,andBMSCgroups,epilepsywasestablishedwithpenicillin(3×107U/kgi.p.×7days).RatsintheBMSCgroupreceivedaBMSCsuspensionderivedfromgreenfluorescentproteinmiceintotherighthippocampalCA1region.RatsinthevehiclecontrolgroupwereinjectedwiththesamevolumeofnormalsalineintothehippocampalCA1region.MAINOUTCOMEMEASURES:Theelectroencephalogramwasusedtomonitorbrainactivity.SurvivalandmigrationofthetransplantedBMSCswasobservedusingfluorescencemicroscopyat1,2,and4weeksaftertransplantation.RESULTS:InBMSCgroup,fluorescentcellswereobservedatthetransplantationsiteandintheadjacenttissue,aswellasinthetissuesurroundingtheneedletract,indicatingthemigrationofimplantedcells.Fluorescentcellswerenotdetectedinthevehiclecontrolgroup.Theelectroencephalogramofthecontrolanimalsexhibited7-9Hzαwaves,withawaveamplitude<50μV.Inthemodelandvehiclecontrolgroups,randomspike-and-wavedischargesofthesharpspike-sharplowwavetyp