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1、ExperimentalNeurology194(2005)467–475www.elsevier.com/locate/yexnrRetinoicacidinducedmyelomeningoceleinfetalrats:CharacterizationbyhistopathologicalanalysisandmagneticresonanceimagingE.Danzer,U.Schwarz,S.Wehrli,A.Radu,N.S.Adzick,A.W.Flake*TheChildren
2、’sHospitalofPhiladelphia,TheChildren’sInstituteforSurgicalScience,TheUniversityofPennsylvaniaSchoolofMedicine,AbramsonResearchCenter,Room1116B,3615CivicCenterBoulevard,Philadelphia,PA19104-4318,USAReceived22November2004;revised11March2005;accepted11M
3、arch2005Availableonline11May2005AbstractThepreventionofhumanneuraltubedefectsbyfolicacidadministrationandthepotentialforfetalsurgicalinterventionformyelomeningocele(MMC)haverenewedinterestinthemolecularpathwaysandpathophysiologyofspinabifida.Animalmo
4、delsforassessmentoftheearlydevelopmentalbiologyandpathophysiologyofthislesionareneeded.Thegoalofthisstudywastodevelopandcharacterizeanon-surgicalratmodelofMMC.Time-datedSprague–Dawleyratsweregavagefeddifferentdosesofretinoicacid(RA)dissolvedinoliveoi
5、latE10(maternaln=55,fetaln=505).Controlanimalsreceivedoliveoilalone(maternaln=20,fetaln=265)orwereuntreated(maternaln=5,fetaln=63).FetuseswereanalyzedbydetailedhistopathologyandMRI.Overall,isolatedMMCoccurredin60.7%(307/505)ofRA-exposedfetusesandnoco
6、ntrols.HistopathologyconfirmedtheentirespectrumofseverityobservedinhumanMMC,rangingfromexposureofthecordwithintactneuralelementstocompletecorddestruction.MRIofthebrainofMMCfetusesconfirmedstructuralchangessimilartohumanswithArnold–Chiarimalformation,
7、includingdownwarddisplacementofthecerebellumtojustabovetheforamenmagnumandcompressionofthedevelopingmedullaintoasmallposteriorfossa.Inconclusion,theRA-inducedratmodelofMMCisdevelopmentallyandanatomicallyanalogoustohumanMMC.Thisrelativelyefficientandc
8、ost-effectivemodelofMMCshouldfacilitateinvestigationofthedevelopmentalbiologyandpathophysiologyofMMC,andmaybeusefulfortheevaluationoffurtherstrategiesforprenataltreatment.D2005ElsevierInc.Allrightsreserved.Keywords:Myelomeningocele;Neuraltube;All-tra
