待看-米诺环素在SCI中的作用

DOI:10.1093/brain/awg178AdvancedAccesspublicationJune4,2003Brain(2003),126,1628±1637

Neuroprotection

signi®cantmice

recoverybyminocyclinefromspinalcordinjuryinJenniferE.A.Wells,1R.JohnHurlbert,1MichaelG.Fehlings2andV.WeeYong1

1Calgary,Department

ofClinicalNeurosciences,Universityof

CorrespondenceNeurosurgery,Calgary,UniversityAlbertaofand2Departmentof

3330E-mail:Hospitalvyong@ucalgary.ca

Drive,to:V.Calgary,W.Yong,Alberta,UniversityCanadaofCalgary,T2N4N1Canada

Toronto,Toronto,Ontario,Summary

Acutethatorinsult,continuesspinalcordtoevolveinjurydays(SCI)andproducestissuedamageingvehicleReducingwithcorrespondingfunctionalweeksafterimpairments.theinitialinjuryofprotection')theingusinghindlimbbeginning1hafterinjury.Behaviouraltest-theBassofunctionwasinitiated3daysafterrecoveryfollowingextentofprogressivetissueloss(`neuro-Functionalscale,andbeenadministrationassessmentsat1weekBeattieBresnahanlocomotorrat-demonstratedusingtheinclinedthatplanetest.oflimited.fromInSCI,SCIshouldresultinabetterthisbuttreatmentoptionshavethusfarfunctionSCIminocyclineinmice.Thisinamelioratingstudy,wehavetestedtheef®cacysemi-syntheticdamagetetracyclinefollowingantibioticacutecomparedandhaslesionwithstrengthsigni®cantlyvehiclefromimprovedbothminocyclinehindlimbcontrols.3to28daysafterinjuryofbeenreportedtoinhibittheexpressionandactivitybymatoryseveralingminocycline,sizeintheandspinaltherecordwaswasFurthermore,grossevidencesigni®cantlyofaxonalreducedproteinases,cytokines,mediatorsoftissueinjury,includingin¯am-rubrospinalasdeterminedusing¯uorogoldlabellingofspar-theMiceFinally,rentlyacomparisontractandofbyBielchowskysilverstain.spinalweresubjectedmakingfreeittoaradicalsandmatrixmetallo-extraduralsuitablecandidatecompressionforstudy.whichcordtheyreceivedusingamodi®edtreatmentaneurysmwitheitherclip,oftheminocyclinefollowingmethylprednisolone,approvedtreatmentminocyclineforacuteagainstthecur-recoveryintheminocycline-treateddemonstratedsuperiorSCIanimals.

behaviouralinhumans,Keywords:in¯ammation;minocycline;neuroprotection;recovery;spinalcordinjury

Abbreviations:MMP=matrixmetalloproteinase;NO=nitricoxide;SCI=spinalcordinjury

SpinalIntroduction

disabilitycordregenerationCurrentininjury(SCI)isaleadingcauseofpermanentdestructionofdamagedstructures.Thebulkofaretherebyreducelimited.treatmentyoungThesteroidoptionsadultsmethylprednisolonefor(Sekhonsigni®cantandrecoveryFehlings,2001).hasfromSCItheprovidingdevelopsatemporaloverdayswindowtoweeksofopportunityafterthetissuetoinsult,limit2001;thatspreadfromHall,swelling2001),andbutdecreaseitsef®cacyin¯ammationis(Chikawabeenusedetalto.,equatedtherescueofdamage.ofasfewAnotheras10%impetusofspinalforneuroprotectioncordisfavourablesomeclinicaltrialshasfailedtocontroversialasdataFehlingswithsigni®cantfunctionalrecovery(Blight,axonscanbelong-termeffects(Hurlbert,2000;Bracken,demonstrate2002).de®nitiveCurrentrehabilitativetreatmentcellSpeci®candmoleculesTator,1995).

1983;havebeenidenti®edbutthebene®tphysiotherapystrategiesinSCIarelimitedtoofinthehopeofrestoringfunction,receptorsdeathcalcium(Liufollowingetal.,SCI.1991),Over-stimulationthatresultinginahighofcontributeglutamatetodisruptionPermanentofwhitedisabilitythisisoftenmatterinspinalminimalandhighlyvariable.tracts,cordtraumaresultsfromcaspases,ionsintothecell,activatesain¯uxofandbreakdownphospholipasesandendonucleasesvarietythatofproteases,promoteSCIextensiveincludepreventionneuronalandoftissueaxonaldeathlossloss.ofoligodendrocytes(neuroprotection)ApproachestotreatandIn¯ammationofcellSchwab,1994)andconstituentsandthematrixelevationincludingplasmamembrane.metalloproteinasesofcytokines(Dusart(MMPs)

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