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27 个结果
  • 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.

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  • 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

  • 标签: 干细胞生物学 人胚胎干细胞 阿尔茨海默氏病 肺部疾病 重新编程 体细胞
  • 简介:Cancertreatmentssuchaschemotherapyandradiotherapyarewidelyusedtotreatprimaryandmetastaticcancers.Epidemiologicalstudieshavedemonstratedthatthesetypesoftreatmentcaneffectivelyandsuccessfullyextendthelifespanofcancerpatients,buttheyarealso

  • 标签: 癌症治疗 海马 放射治疗 流行病学 癌症患者 神经系统
  • 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.

  • 标签: 氧化应激 细胞死亡 中风 级联 阿尔茨海默氏病 帕金森氏病
  • 简介:Peripheralnerveinjuries(PNI)areamajorclinicalproblem.Ingeneral,PNIresultsfrommotorvehicleaccidents,lacerationswithsharpobjects,penetratingtrauma(gunshotwounds)andstretchingorcrushingtraumaandfractures.ItisestimatedthatPNIoccurin2.8%oftraumapatientsandthisnumberreaches5%ifplexusandrootlesionsarein-

  • 标签: 神经再生 周围神经损伤 导管 管状 运动 疗法
  • 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

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

  • 标签: 脊髓损伤 细胞移植 交感神经 反应 皮肤 慢性
  • 简介:cAMPsignalingandthecontrolofSchwanncellfate:Theubiquitoussecondmessengercyclicadenosinemonophosphate(cAMP)controlsavarietyofcellularresponsesinacelltype-specificandstimulus-dependentmannerthroughanelaboratenetworkofsignalingintermediariesthatconnectstimulationofcellmembranereceptors(typicallyG

  • 标签: 雪旺细胞 cAMP 信号通路 分化 增殖 G蛋白偶联受体
  • 简介:Alzheimer’sdisease(AD)isoneofthemostdevastatingdiseasesaffectingthelifeandhealthofagingpopulation.TwohallmarksofADaresenileplaquesandneurofibrillarytangles,andADiswellknownforthemassivelossofneuronsandimpairedcognitivefunctionsespeciallymemoryloss.Despiteextensivesearchforeffectivetreatment,available

  • 标签: NMDA受体 细胞死亡 N-甲基-D-天冬氨酸 损失 突触 阿尔茨海默病
  • 简介:Thecentralnervoussystem(CNS)containsthetwomostimportantorgans,thebrainandspinalcord,fortheorchestrationofthementalandphysicalactivitiesoflife.Becauseofitsimportance,thehumanbodyhasevolvedbarriersystemstoprotectCNStissuefromtheexternalenvironment.Thisbarrierisamembranecomposedoftightlyapposedcellsandisselectivelypermeabletospecificmoleculesbywayofmembranetransporters.Themajorbarriersinthebrainandtheircorrespondingcellularconstituentsarethebloodbrainbarrier(BBB)composedofendothelialcellsinbrain

  • 标签: 中枢神经系统损伤 神经元损伤 免疫细胞 EMT 结构 俘获
  • 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

  • 标签: 实验性变态反应性脑脊髓炎 嗅鞘细胞移植 运动功能量表 脱髓鞘疾病 动物模型 修复
  • 简介:Tourette'ssyndromeistreatedbybehavioralorpharmacologicaltherapy.However,patientswithmalignantTourette'ssyndromealsoexhibitlife-threateningsymptoms,whichareunresponsivetoconservativetreatmentsorneurosurgicalprocedures,suchasdeepbrainstimulation.Inrecentyears,mesenchymalstemcells(MSCs)haveshowntherapeuticpotentialinmanyneurologicaldiseases.Therefore,thepresentstudyproposedtouseMSCtransplantationasanoveltherapyforTourette'ssyndrome.StereotypicbehaviorsinTourette'ssyndromeratsdecreasedsignificantlyat21daysafterhumanMSCstransplantationintothestriatum.ImmunohistochemistryanalysesrevealedsurvivaloftransplantedhumanMSCsanddifferentiationintoneuronsandastrocytesintheratbrain.ResultssuggestthatintrastriataltransplantationofhumanMSCscouldprovidetherapeuticpotentialforTourette'ssyndrome.

  • 标签: 骨髓间质干细胞 体细胞移植 综合征 动物模型 骨髓基质干细胞 药物治疗
  • 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

  • 标签: 脂多糖活性 BV2 骨髓间叶干细胞 小胶质
  • 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.

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