简介:BACKGROUND:Duetothelackofautografttransplantrejection,Schwanncells(SCs)canpromotetheproliferationofembryonicstemcellsandtheinductionofdopaminergicneurons.Mesencephalicstemcellscanbeinducedtoproducedopaminergicneurons.Thetherapeuticeffectsofco-graftsofSCsandneuralstemcells(NSCs)deservesfurtherstudyandverificationinParkinsoniananimalmodels.OBJECTIVE:ToinvestigatetheeffectsofSchwanncellsandmesencephalicNSCco-graftsinParkinsoniananimalmodelsonanimalbehaviorandhistology.DESIGN:Randomizedcontrolledexperiment.SETTING:FudanUniversity;InstituteofNeuroscience,ChineseAcademyofSciences.MATERIALS:ThefollowinganimalswereobtainedfromtheExperimentalAnimalCenter,ShanghaiInstituteforBiologicalScience,ChineseAcademyofSciences:5Sprague-Dawleyrats,embryonicday(E)13-16;16neonatalSprague-Dawleyrats,postnatalday1-3;and18adultSDratsofbothgenders.Animalexperimentationmetanimalethicalapproval.METHODS:TheexperimentwasperformedattheDepartmentofAnatomy,HistologyandEmbryology,ShanghaiMedicalCenter,FudanUniversityfromSeptember2005toJanuary2007.ThemesencephalicNSCswereobtainedfromthebrainsofSDratsatE13-16,andSCswereharvestedfromthesciaticnervesofneonatalratsatday1-3.Hemiparkinsonianrats(n=18)wereselectedfortransplantationafterestimatingrotationalbehaviorinresponsetoapomorphineandwererandomlyassignedtothreegroups:controlgroup,NSCgroup,andco-graftgroup.Therewere6ratsineachgroup.Eitherphosphatebufferedsaline(PBS),NSCs,orSCsplusNSCsweretransplantedintotherightneostriatumofParkinsonianrats,respectively.MAINOUTCOMEMEASURES:①Rotationalbehaviorwasinducedbyapomorphine(0.05mg/kg,i.p.)2,4,6,8,and10weeksaftertransplantation,andthenumberofrotationswerecounted.②Differentiationandsurvivalofdopaminergicneuronsintherightneostriatumwerequantifiedbytyrosinehydroxylaseimmu
简介:目的探讨MMP-2和TIMP-2与胶质瘤侵袭性及恶性表型之间的关系及其意义.方法采用Elivision二步免疫组织化学法染色观察MMP-2和TIMP-2在46例不同恶性度胶质瘤及10例正常脑组织中的表达并用德国LeicaQ550cw图像分析系统测其灰度值作为表达强度的量化指标.结果在对照组、低度及高度恶性胶质瘤中,MMP-2的阳性表达率分别为10%、63.6%和95.8%;在对照组、低度及高度恶性胶质瘤中,TIMP-2的阳性表达率分别为10%、36.3%和37.5%.MMP-2在Ⅰ、Ⅱ级和Ⅲ、Ⅳ级胶质瘤中平均灰度值分别为173.27±13.26和98.63±18.20;TIMP-2在Ⅰ、Ⅱ级和Ⅲ、Ⅳ级胶质瘤中平均灰度值分别为210.44±12.95和205.65±9.75.结论MMP-2表达随胶质瘤恶性程度增加而增强,可作为胶质瘤恶性表型及侵袭性指标之一.TIMP-2表达在正常脑组织及不同级别胶质瘤中无明显差异.MMP-2/TIMP-2的比值与胶质瘤侵袭性密切相关.
简介:RolesofKeap1-Nrf2pathwayinbrain:NeuronalsurvivalandneurogenesisareimpairedinneurodegenerativediseasessuchasParkinson’sdiseaseandAlzheimer’sdisease(Winneretal.,2011).Geneticup-regulationofgrowthfactorsenhancedneuronalsurvivalandneurogenesis,improvedneuronalfunctionsandhalteddiseaseprogressioninanimalmodelsofAlzheimer’sdisease
简介:BACKGROUND:Mailuoning,aChineseherb,hasbeenwidelyusedinChinatotreatacuteischemicstroke,andthemajorcomponentexhibitsanti-oxidativeeffects.However,thepreciseanti-oxidationpathwayremainsuncertain.OBJECTIVE:TovalidatetheprotectiveeffectsofMailuoningonH2O2-inducedprimarycorticalneuroninjuryinembryonicmice.DESIGN,TIMEANDSETTING:ComparativeobservationandinvitroexperimentswereperformedattheJiangsuKeyLaboratoryforMolecularMedicinefromJanuary2008toSeptember2009.MATERIALS:Mailuoning(NanjingJinlingMedicalCompany,China),reactiveoxygenspecies(ROS)kit(BeyotimeBiotechnology,China),superoxidedismutase(SOD),Cu/ZnSODkit,malondialdehyde(MDA)kits(NanjingJiancheng,China),mitochondrialmembranepotential(GMS10013.1,GENMED,USA)andcatalaseactivityassaykit(BeyotimeBiotechnology,China)wereutilizedforthepresentstudy.METHODS:MouseembryoniccorticalneuronswereisolatedandculturedwithculturemediumcontainingH2O2(80μmol/L)and/orMailuoning(1.25μg/mL)for24hours.MAINOUTCOMEMEASURES:Neuronalviabilityanddeathweredetectedbymethylthiazolyltetrazdiumandflowcytometry;ROSproductionwasdeterminedbyflowcytometry;mitochondrialmembranepotentialwasdetectedusingfluorescentstaining;SODactivitywasdetectedusingamodifiednitrobluetetrazoliummethod;Cu/ZnSODandcatalaseactivitywasdetectedbyspectrophotometry;andMDAwasdeterminedusingthelipidperoxidationmethod.RESULTS:H2O2increasedROSproductionandMDAconcentration(P<0.05),anddecreasedmitochondrialmembranepotential,SOD,Cu/ZnSODandcatalaseactivity(P<0.05);thenumberofsurvivingneurons(P<0.05)wasalsoreduced.Mailuoningreversedthesechanges.CONCLUSION:MailuoningprotectsH2O2-inducedinjuryincorticalcellsbyinhibitingROSandMDA,increasingdepolarizationofmitochondrialmembrane,andenhancingSODandcatalaseactivity.
简介:目的探讨320排CT血管成像(CTA)对硬脊膜动静脉瘘(SDAVF)的诊治价值。方法回顾性分析11例SDAVF病人的临床资料,均行320排CTA及DSA检查,以病变的定性诊断、供血动脉、瘘口、引流静脉的显示情况及手术治疗效果等作为观察指标进行分析。结果320排CTA对11例病人均做出正确诊断,DSA首次检查漏诊2例,经行320排CTA获得相关图像信息后再行DSA检查发现病变。所有病人经手术治疗后随访3个月-2年,短期预后均良好,但术后9-12个月出现神经功能障碍加重3例。结论320排CTA可良好地立体显示SDAVF病灶的特征及其周围的骨性解剖结构,但其不能动态显示病灶的血流动力学改变,尚不能取代DSA检查。
简介:目的评价320排动态容积CT在脑静脉窦血栓形成(CVST)诊断中的应用价值。方法对12例CVST患者行320排头颅CT一站式检查,包括CT平扫、各期增强,然后将动态容积原始数据重建出容积图像,传入Vitreafx工作站,处理获得动脉期、动静脉混合期、静脉期及静脉窦期血管重建图像。结果12例CVST中10例累及多个静脉窦,2例为单个静脉窦受累。CVST直接征象有:CT平扫显示为“高密度三角征”(3例),“带征”(1例),CT增强显示“空三角征”(4例);间接征象有:血栓形成部位邻近脑组织水肿(3例),静脉性脑梗死(4例),静脉性脑出血(5例)。12例CVST中静脉期图像均可见静脉窦不规则狭窄或闭塞,可见特征性的“空槽征”。12例患者的CVST均经3D—DSA证实。结论与传统影像学检测方法比较,320排动态容积cT检查无创伤、时间短和辐射剂量少,对CVST的诊断具有重要价值。
简介:目的研究刺五加多糖(ASPS)对H2O2诱导的海马神经元凋亡的影响及其机制。方法采用H2O2诱导大鼠海马神经元凋亡。采用末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记法检测细胞凋亡率、免疫组化法检测caspase-3蛋白的表达、逆转录PCR法检测caspase-3mRNA的表达。结果H2O2作用后,海马神经元凋亡率、caspase-3蛋白和mRNA表达水平均显著增高(P〈0.05);给予ASPS干预后,均显著下降(P〈0.05);而且,随ASPS剂量增加,作用效果显著增强(P〈0.05)。结论ASPS具有抑制氧化应激损伤诱导神经细胞凋亡作用,其机制与下调caspase-3mRNA的表达有关。
简介:Thismini-reviewpresentstheauthors'visiononthecurrentstatusandfuturetrendsinthedevelopmentofneuroprotectiveagentsworkingviaactivationofnuclearfactorerythroid2-relatedfactor2(Nrf2),andinparticular,viadisruptionofNrf2-Keaplinteraction.Therearetwoopposite'chemical'mechanismsunderlyingsuchactivation:thefirstoneisanon-specificcovalentmodificationofKeap1thiols,resultinginsideeffectsofvariedseverity,andthesecondoneistheshiftoftheNrf2-Kelch-likeECHassociatedprotein-1(Keap1)bindingequilibriuminthepresenceofacompetitiveandchemicallybenigndisplacementagent.Atthispoint,nodisplacementactivatorsexhibitsufficientbiologicalactivityincomparisonwithcommonNrf2activatorsworkingviaKeaplthiolmodification.Hence,thehopeintherapeuticsisnowlinkedtotheFDAapproveddimethylfumarate,whosederivative,monomethylfumarate,aswedemonstratedrecently,ismuchlesstoxicbutequallybiologicallypotentandanidealcandidateforclinicaltrialsrightnow.AnewlyemergingplayerisanuclearinhibitorofNrf2,BTBdomainandCNChomolog1(Bach1).ThecommerciallydevelopedBachlinhibitorsarecurrentlyunderinvestigationinourlaboratoryshowingpromisingresults.Inourviewpoint,theperfectfuturedrugwillpresentthecombinationofadisplacementactivatorandBachlinhibitortoinsuresafetyandefficiencyofNrf2activation.
简介:苯妥英(PHT)为临床上最常用的第一线抗癫痫药,但个体间对PHT代谢呈现较大差异.目前证实细胞色素氧化酶P450(CYP)2C9/19是体内参与PHT羟化的主要代谢酶.人群CYP2C9/19遗传基因呈多态性,从而引起对PHT代谢个体间较大差异,部分人群对PHT呈强代谢(EM),另一部分人群呈弱代谢(PM),了解这些知识对临床用药十分重要.本文试对该方面内容进行综述.
简介:BACKGROUND:ElectrophysiologycanprovetheintegrationofafferentinformationfromthestomachmeridianofFoot-Yangminginthenucleustractussolitarius(NTS)andobjectivelydescribethespecificassociationbetweenmeridianvesselsandZangFuorgans.OBJECTIVE:ToinvestigatetheeffectsofafferentinformationfromacupunctureatSibai(ST2)acupointonneuronaldischargeinratNTS.DESIGN,TIMEANDSETTING:Arandomized,controlled,animalexperimentwasperformedattheKeyLaboratoryofMeridian-VesselsandZangFuOrgans,TraditionalChineseMedicineUniversityofHunan,StateAdministrationofTraditionalChineseMedicine,andKeyLaboratoryofAcupuncture,Moxibustion,andtheBiologicalInformationofHunanHigherEducationInstitutes,betweenDecember2005andOctober2008.MATERIALS:Atotalof52SpragueDawleyrats,ofeithergender,aged4months,wereincludedinthisstudy.Acupunctureneedlesof0.32mm(diameter)×40mm(length)wereused.METHODS:Anextracellularrecordingprotocolwasapplied.TheSibai(ST2)acupointinthestomachmeridianofFoot-Yangmingwasusedasanacupuncturepoint(acupoint).Simultaneously,Dicang(ST4)andNetting(ST44)acupointsinthestomachmeridianofFoot-Yangming,Quanliao(SI18)acupointinthesmallintestinemeridianofHand-Taiyang,andanon-acupointlateraltoSibai(ST2)acupoint,wereselectedascontrols.TheSibai(ST2)acupointwasstimulatedfor30seconds,byhandacupuncturethroughtwirlingandrotating,todeterminetheneuronsrespondingtobodysurfacestimulationintheNTS.MAINOUTCOMEMEASURES:FrequencyofrespondingNTSneuronsafteracupunctureatfouracupointsincludingSibai(ST2),Dicang(ST4),Neiting(ST44)andQuanliao(SI18)andonenon-acupoint.RESULTS:ThefrequencyofrespondingNTSneuronswassignificantlyhigherafteracupunctureatSibaithanatcontrolsitesincludingtheDicang(ST4),Netting(ST44)andQuanliao(SI18)acupointsandatthenon-acupoint(P<0.01).ThefrequencyofrespondingNTSneuronsatDicang(ST4)andQuanliao(SI