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ID:20018604
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时间:2018-10-09
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1、Title:MicrotubuleStabilizationReducesScarringandCausesAxonRegenerationAfterSpinalCordInjuryFaridaHellaletal.Science331,928(2011);DOI:10.1126/science.1201148Reporter:***Supervisor:***SecondarySupervisor:***BackgroundsHypertrophicscarringandpoorintrinsic
2、axongrowthcapacityconstitutemajorobstaclesforspinalcordrepair.Microtubuledynamicsregulatekeyprocessesduringscarring,includingcellproliferation,migration,anddifferentiationaswellasintracellulartraffickingandsecretionofextracellularmatrix(ECM)molecules(1,
3、2).Moreover,moderatemicrotubulestabilizationpreventsaxonalretractionandswellingoftheaxontipaftercentralnervoussystem(CNS)injury(3)andstimulatesaxongrowthofculturedneurons(4),enablingthemtoovercomethegrowthinhibitoryeffectofCNSmyelin(3).AssumptionsTheyhy
4、pothesizedthatmoderatemicrotubulestabilizationwithTaxol,anapproveddrug,wouldfacilitateaxonalregenerationafterspinalcordinjury(SCI)bydecreasingscarformationandenhancingintrinsicaxonalgrowth.MethodsTheyfirstexaminedwhetherTaxoltreatmentreducedscarringafte
5、rSCI.Adultratsunderwentadorsalhemisectionattheeighththoracicspinalcordlevel;Taxol(256ng/day)wascontinuouslydeliveredattheinjurysiteusinganintrathecalcatheterconnectedtoanosmoticminipump.Whathappened7dayslater?FaridaHellaletal.Science2011;331:928-931Publ
6、ishedbyAAASFig.1Taxoldecreasesscarringinducedbyspinalcordinjury.(A)Representationoflesionedspinalcord(box).(BandC)Midsagittalsectionsoflesionsitefromratstreatedwith(B)vehicleor(C)Taxol(256ng/day)7daysafterinjury.Scalebars,300μm.(D)Taxolsignificantlydecr
7、easesfibroticscarring(expressedaspercentageofvehiclecontrol;n=12ratspergroup;**P=0.002;two-tailedttest)withoutaffectingglialcompaction(28daysafterinjury)(E)orinjurysize(F)(n=7to10ratspergroup;P=0.951;two-tailedttest).Dataexpressedasmean±SEM.GFAP,glialfi
8、brillaryacidicprotein.FigureS1:Taxoldecreasesfibronectin,NG2proteoglycanandcollagenIVaccumulationinducedbyspinalcordinjury(A)Representationoflesionedspinalcord(box).(B-D)Mid-saggitalsectionsoflesionsitefromrattreatedwithVehicleo
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