简介:Thehippocampalregionofthebrainisimportantforencodingenvironmentinputsandmemoryformation.However,theunderlyingmechanismsareunclear.ToinvestigatethebehaviorofindividualneuronsinresponsetosomatosensoryinputsinthehippocampalCA1region,werecordedandanalyzedchangesinlocalfieldpotentialsandthefiringratesofindividualpyramidalcellsandinterneuronsduringtailclampinginurethane-anesthetizedrats.Wealsoexploredthemechanismsunderlyingtheneuronalresponses.Somatosensorystimulation,intheformoftailclamping,changedlocalfieldpotentialsintothetarhythm-dominatedwaveforms,decreasedthespikefiringofpyramidalcells,andincreasedinterneuronfiring.Inaddition,somatosensorystimulationattenuatedorthodromic-evokedpopulationspikes.TheseresultssuggestthatsomatosensorystimulationsuppressestheexcitabilityofpyramidalcellsinthehippocampalCA1region.Increasedinhibitionbylocalinterneuronsmightunderliethiseffect.Thesefindingsprovideinsightintothemechanismsofsignalprocessinginthehippocampusandsuggestthatsensorystimulationmighthavetherapeuticpotentialforbraindisordersassociatedwithneuronalhyperexcitability.
简介:BACKGROUND:Previousstudieshaveshownthatthemitochondrialstructureandfunctionaredamagedinanimalmodelsofepilepsy.Inaddition,theBcl-2proteiniscapableofregulatingmitochondrialstability.OBJECTIVE:ToobserveandvalidatechangesinmitochondrialstructureandBcl-2expression,andtoanalyzethesecharacteristicsinthehippocampalCA3regionofratmodelsofepilepsy.DESIGN,TIMEANDSETTING:Thisrandomized,controlled,animalexperimentwasperformedattheLaboratoryofElectronMicroscopyandDepartmentofHistologyandEmbryology,LuzhouMedicalCollegebetween2007and2008.MATERIALS:CoriamyrtinwasprovidedbythePharmacyFactoryofWestChinaUniversityofMedicalSciences.TheprimaryandsecondaryantibodieswereprovidedbyZhongshanGoldenbridgeBiotechnology,Beijing.METHODS:Atotalof44adult,male,SpragueDawleyratswererandomlydividedintocontrol(n=11)andepilepsy(n=33)groups.Ratsintheepilepsygroupwereinducedbycoriamyrtin(50μg/kg),whichwasinjectedintothelateralventricles.Theratswerethenobservedat3,6,and24hoursafterepilepsyinduction,with11ratsateachtimepoint.Epilepsywasnotinducedinratsfromthecontrolgroup.MAINOUTCOMEMEASURES:PathologicalchangesinthehippocampalCA3regionwereobservedbylightmicroscopy;Bcl-2expressionwasanalyzedbyimmunohistochemistry;andmitochondrialchangesinthehippocampuswereobservedundertransmissionelectronmicroscopy.RESULTS:(1)ThecontrolgroupdisplayedverylittleBcl-2proteinexpressioninthehippocampalCA3region.However,after3hoursofepilepsy,expressionwasvisible.By6hours,expressionpeakedandthensubsequentlydecreasedafter24hours,butremainedhigherthanthecontrolgroup(P<0.05).(2)Mitochondriaweredamagedtovaryingdegreesintheepilepsygroups.Forexample,mitochondriaedema,cristaespaceincrease,anddisappearanceofmitochondriawereapparent.Moreover,mitochondrialdamageoccurredpriortopathologicalchangesintheneuronsandnucleolus.CONCLUSION:
简介:BACKGROUND:Animalexperimentshaveconfirmedthatbonemarrowstromalcell(BMSC)transplantationcanserveasatreatmentforepilepsy.OBJECTIVE:BMSCsderivedfromgreenfluorescentprotein(GFP)miceweretransplantedintothehippocampalCA1regionofepilepticrats.Theaimofthestudywastorecordelectroencephalogram(EEG),analyzesurvivalandmigrationofBMSCs,andvalidatetheeffectofBMSCtransplantationforthetreatmentofepilepsy.DESIGN,TIMEANDSETTING:ArandomizedblockdesignexperimentwasperformedattheInstituteofNeuroscience,KunmingMedicalCollegefromMarch2005toFebruary2006.MATERIALS:HomozygousC57BL/6CrSlcTgN(acr-EGFP)OsbC14-Y01-FM131mice,8-12weeksofage,wereselectedforpreparationofcellsuspension.SpragueDawleyratswereselectedforestablishingepilepsymodels.METHODS:Ratswererandomlydividedinto4groups:control(n=8),model(n=8),normalsaline(n=24),andBMSC(n=24).Inthemodel,normalsaline,andBMSCgroups,epilepsywasestablishedwithpenicillin(3×107U/kgi.p.×7days).RatsintheBMSCgroupreceivedaBMSCsuspensionderivedfromgreenfluorescentproteinmiceintotherighthippocampalCA1region.RatsinthevehiclecontrolgroupwereinjectedwiththesamevolumeofnormalsalineintothehippocampalCA1region.MAINOUTCOMEMEASURES:Theelectroencephalogramwasusedtomonitorbrainactivity.SurvivalandmigrationofthetransplantedBMSCswasobservedusingfluorescencemicroscopyat1,2,and4weeksaftertransplantation.RESULTS:InBMSCgroup,fluorescentcellswereobservedatthetransplantationsiteandintheadjacenttissue,aswellasinthetissuesurroundingtheneedletract,indicatingthemigrationofimplantedcells.Fluorescentcellswerenotdetectedinthevehiclecontrolgroup.Theelectroencephalogramofthecontrolanimalsexhibited7-9Hzαwaves,withawaveamplitude<50μV.Inthemodelandvehiclecontrolgroups,randomspike-and-wavedischargesofthesharpspike-sharplowwavetyp
简介:BACKGROUND:Calciumion(Ca2+)overloadplaysanimportantroleincerebralischemia/reperfusioninjury.Anisodamine,atypeofalkaloid,canprotectthemyocardiumfromischemiaandreperfusioninjurybyinhibitingintracellularcalcium[Ca2+]ioverload.OBJECTIVE:Toinvestigateeffectsofanisodamineon[Ca2+]iconcentrationandcortexultrastructurefol-lowingacutecerebralischemia/reperfusioninrabbits.DESIGN,TIMEANDSETTING:RandomizedandcontrolledtrialwasperformedattheDepartmentofEmergency,TongjiHospital,TongjiMedicalCollegeofHuazhongUniversityofScienceandTechnologyfromSeptembertoDecember2006.MATERIALS:Fortyhealthyrabbitswereusedtoestablishmodelsofacutecerebralischemia/reperfusion.AnisodaminewasprovidedbyLianyungangDongfengPharmaceuticalFactory;Fura-2waspurchasedfromNanjingJianchengBioengineeringInstitute;dual-wavelengthfluorescentspectrophotometrysystemandDM-300softwarewereprovidedbyBio-Rad,USA;OPTON-EM10CtransmissionelectronmicroscopewasproductofSiemens,Germany.METHODS:Fortyrabbitswererandomlydividedintothefollowinggroups:shamoperation,ischemia,ischemia/reperfusion,andanisodamine,withtenrabbitsineachgroup.Modelsofcompletecerebralischemiainjurywereestablished.Inaddition,bloodwascollectedfromthefemoralarteryofratsintheischemia/reperfusionandanisodaminegroupstoinducehypotensionandestablishreperfusioninjurymodels.Thebilateralcommoncarotidarteryclampwasremovedfromtheanisodaminegroup20minutesafterischemia,andanisodamine(10mg/kgbodymass)wasinjectedviathefemoralvein.Rabbitsintheshamoperationgroupunderwentonlyvenouscannulation.MAINOUTCOMEMEASURES:[Ca2+]iconcentrationwasdeterminedusingadual-wavelengthfluorescentspectrophotometrysystem,andcorticalultrastructurewasobservedfollowinguranyl-leadcitratestaining.RESULTS:Thelevelsof[Ca2+]iintheischemiaandischemia/reperfusiongroupsweresignificantlyin-creased,c
简介:目的:探讨不同牛津郡社区卒中项目(OCSP)亚型急性脑梗死患者血清Fractalkine(FKN)浓度的变化。方法:45例急性脑梗死患者按OCSP分型分为完全前循环梗死(TACI)组、部分前循环梗死(PACI)组、后循环梗死(POCI)组和腔隙性梗死(LACI)组。采用酶联免疫吸附法检测发病1~3d、7d、14d和28d时血清FKN浓度,比较各组间的差异。分析FKN浓度与相应时间点美国国立卫生研究院卒中量表(NIHSS)评分和3个月时Barthel指数(BI)的相关性。结果:各种亚型急性脑梗死患者血清FKN浓度均升高,TACI组最为显著;在不同时间点,血清FKN浓度变化大致为TACI〉PACI〉LACI〉POCI,与相应时间点NIHSS评分呈正相关,与3个月时BI呈负相关。结论:血清FKN浓度的变化可能提示急性脑梗死各OCSP亚型患者炎症损伤的差异,并影响神经功能缺损程度和患者3个月时的转归。
简介:目的测定脑梗死及脑出血疾病血清NO含量并探讨它们的关系.方法采用硝酸还原酶法分别测定35例脑梗死病人,35例脑出血病人及35例正常人血清中NO的含量,以探讨三者之关的关系.结果显示脑梗死组血清中NO含量为(144.0±22.9)μmol/L,脑出血组血清中NO含量为(138.0±24.6)μmol/L,正常人组血清中NO含量为(768±8.9)μmol/L.本实验所测定样本均数间比较应用t检验进行统计学处理后得出:P1(脑梗死组与正常对照组)<0.01,P2(脑出血组与正常对照组)<0.01,P3(脑梗死组与脑出血组)=0.611.结论脑血管疾病(脑梗死及脑出血)患者发病后NO即迅速升高;二者血清中NO含量与正常人血清中NO含量比较有极显著差异,而二者之间比较并无显著差异.这是由于发病后二者由于不同原因导致脑细胞缺血,导致谷氨酸(Glu)释放增加,使N-甲基-天冬氨酸(NMDA)受体激活,Ca++通路开放,大量Ca++内流并与钙调素(CaM)结合,激活NO合成酶(NOS),其中iNOS的激活无需Ca++,生成大量的NO.它在脑梗死疾病早期起到保护作用,而在脑出血疾病及脑梗死疾病后期产生毒性作用.
简介:Heatshockprotein70(HSP70)maintainsCa~(2+)homeostasisinPC12cells,whichmayprotectagainstapoptosis;however,themechanismsofneuroprotectionareunclear.Therefore,inthisstudy,weexaminedCa~(2+)levelsinPC12cellstransfectedwithanexogenouslentiviralHSP70geneexpressionconstruct,andwesubsequentlysubjectedthecellstoischemia-hypoxia/reoxygenationinjury.HSP70overexpressionincreasedneuronalviabilityandATPaseactivity,anditdecreasedcellularreactiveoxygenspecieslevelsandintracellularCa~(2+)concentrationafterhypoxia/reoxygenation.HSP70overexpressionenhancedtheproteinandmRNAexpressionlevelsofsarcoplasmic/endoplasmicreticulumCa~(2+)-ATPase(SERCA),butitdecreasedtheproteinandmRNAlevelsofinositol1,4,5-trisphosphatereceptor(IP3R),therebyleadingtodecreasedintracellularCa~(2+)concentrationafterischemia-hypoxia/reoxygenation.TheseresultssuggestthatexogenousHSP70protectsagainstischemia-hypoxia/reoxygenationinjury,atleastinpart,bymaintainingcellularCa~(2+)homeostasis,byupregulatingSERCAexpressionandbydownregulatingIP_3Rexpression.
简介:Thestudyaimstoconfirmtheneuroregenerativeeffectsofbacterialmelanin(BM)oncentralnervoussysteminjuryusingaspecialstainingmethodbasedonthedetectionofCa~(2+)-dependentacidphosphataseactivity.Twenty-fourratswererandomlyassignedtoundergoeitherunilateraldestructionofsensorimotorcortex(groupI;n=12)orunilateralrubrospinaltracttransectionatthecervicallevel(C3–4)(groupⅡ;n=12).Ineachgroup,sixratswererandomlyselectedaftersurgerytoundergointramuscularinjectionofBMsolution(BMsubgroup)andtheremainingsixratswereintramuscularlyinjectedwithsaline(salinesubgroup).NeurologicaltestingconfirmedthatBMacceleratedtherecoveryofmotorfunctioninratsfrombothBMandsalinesubgroups.Twomonthsaftersurgery,Ca~(2+)-dependentacidphosphataseactivitydetectionincombinationwithChilingarian'scalciumadenosidetriphosphatemethodrevealedthatBMstimulatedthesproutingoffibersanddilatedthecapillariesinthebrainandspinalcord.TheseresultssuggestthatBMcanpromotetherecoveryofmotorfunctionofratswithcentralnervoussysteminjury;anddetectionofCa~(2+)-dependentacidphosphataseactivityisafastandeasymethodusedtostudytheregeneration-promotingeffectsofBMontheinjuredcentralnervoussystem.
简介:目的观察胰岛素对全脑缺血后海马CA1区神经元凋亡及大鼠学习记忆力改变的影响,探讨胰岛素对全脑缺血后海马CA1区神经元产生中枢直接保护作用的机理.方法利用4-VO法制作大鼠全脑缺血模型.造成脑缺血15min后行再灌注,于再灌注后即刻经脑室注入1U胰岛素,利用免疫组化及原位标记法分别于全脑缺血后1、3d观察海马CA1区Bcl-2、Bcl-xl蛋白表达及神经元凋亡的情况;缺血后8周,利用"Y"型迷宫测试大鼠的学习记忆功能.结果全脑缺血后3d,缺血组大鼠海马CA1区Bcl-2、Bcl-xl蛋白的表达呈阴性,海马CA1区原位标记阳性细胞计数为143.5±11.6.治疗组大鼠海马CA1区Bcl-2、Bcl-xl蛋白呈阳性表达,海马CA1区原位标记阳性细胞计数为75.6±6.7.全脑缺血后8周,治疗组大鼠学习记忆力明显好于缺血组.结论全脑缺血后脑室内注入胰岛素可促进海马CA1区Bcl-2、Bcl-xl蛋白表达,减少神经元的凋亡,进而减轻脑缺血后大鼠的学习记忆力损害,这可能是其对全脑缺血后海马CA1区神经元产生中枢直接保护作用主要机理之一.
简介:目的探讨脂蛋白(a)(Lp(a))是否为缺血性卒中的危险因素,以及Lp(a)水平与缺血性脑卒中类型和预后的关系。方法将缺血性脑卒中患者按急性卒中治疗低分子肝素试验.TOAST)分型标准分为心源性脑栓塞(CE)、大动脉粥样硬化性卒中(LAA)、小动脉卒中(SAA)、其他原因引发的缺血性卒中(SOE)和原因不明的缺血性卒中(SUE)。以同期入院的非脑卒中患者(经头颅CT或磁共振排除)作为对照组。病例组和对照组均于入院次日清晨空腹抽取静脉血,测定Lp(a)及其他各项血脂指标,并于入院及病程两周时分别行NHISS评分评估神经功能缺损程度,分析Lp(a)与卒中类型及NIHSS评分之间的关系。结果缺血性脑卒中组Lp(a)浓度及异常率均高于对照组(P〈0.05),Lp(a)进入大动脉粥样硬化卒中患病因素的回归方程Lp(a)水平与卒中患者的NIHSS评分无相关性(P〉0.05)。结论高浓度Lp(a)可能参与了缺血性脑卒中的发生,并且可能是大动脉粥样硬化性卒中发生的危险因素,但与神经功能缺失程度和早期功能修复无关。
简介:Ischemicpreconditioningelicitedbyanon-fatalbriefocclusionofbloodflowhasbeenappliedforanexperimentaltherapeuticstrategyagainstasubsequentfatalischemicinsult.Inthisstudy,weinvestigatedtheneuroprotectiveeffectsofischemicpreconditioning(2-minutetransientcerebralischemia)oncalbindinD28kimmunoreactivityinthegerbilhippocampalCA1areafollowingasubsequentfataltransientischemicinsult(5-minutetransientcerebralischemia).AlargenumberofpyramidalneuronsinthehippocampalCA1areadied4daysafter5-minutetransientcerebralischemia.IschemicpreconditioningreducedthedeathofpyramidalneuronsinthehippocampalCA1area.CalbindinD28kimmunoreactivitywasgreatlyattenuatedat2daysafter5-minutetransientcerebralischemiaanditwashardlydetectedat5dayspost-ischemia.IschemicpreconditioningmaintainedcalbindinD28kimmunoreactivityaftertransientcerebralischemia.Thesefindingssuggestthatischemicpreconditioningcanattenuatetransientcerebralischemia-causeddamagetothepyramidalneuronsinthehippocampalCA1areathroughmaintainingcalbindinD28kimmunoreactivity.
简介:目的研究重组人促红细胞生成素(recombinanthumanerythropoietin,r—huEPO)对颅脑创伤患者血清神经元特异性烯醇化酶(neuron—specificenolase,NSE)表达的影响,评价其神经保护作用。方法纳入住院治疗的颅脑创伤患者32例,随机分配到对照组与治疗组,治疗组于规定时间皮下注射r—huEPO。对照组不予r—huEPO处理,其他治疗两组相同。比较治疗后两组患者GCS评分、颅内压及脑水肿变化情况;两组均在研究时间静脉采血,利用双抗体夹心酶联免疫(ELISA)法分析各组NSE变化。结果从临床征象比较,治疗组患者较对照组恢复较好;两组患者血清NSE均随时间变化表达不同,治疗组血清NSE含量低于对照组,差异有统计学意义(P〈0.05)。结论NSE是较为敏感特异的神经元和神经胶质细胞损伤的指标,利用r—huEPO进行红细胞动员,可通过各种机制抑制颅脑创伤后的继发病理损害及其过度炎症反应,对神经系统损伤具有保护作用。
简介:Thepresentstudywasdesignedtodeterminemicrotubule-associatedprotein-2andsynaptophysinexpressioninthehippocampalCA3regioninaratmodelofmiddlecerebralarteryocclusion.TheratsweretreatedwithacupunctureatBaihui(GV20),Qubin(GB7),andQianding(GV21)points,inadditiontoexercisetraining.Resultswerecomparedwithratsundergoingexercisetrainingonly.TheY-mazemethodandimmunohistochemistryrevealeddecreasederrorfrequencyofpassingthroughY-maze,aswellassignificantlyincreasedmicrotubule-associatedprotein-2andsynaptophysinexpression,intheacupuncturewithexercisetraininggroupcomparedwiththemodelandexercisetraininggroupsafter5weeks.Microtubule-associatedprotein-2andsynaptophysinexpressionsnegativelycorrelatedwitherrorfrequencyofpassingthroughtheY-maze.Theseresultssuggestedthatacupuncturecombinedwithexercisetrainingimprovedlearningandmemoryfunctionsinaratmodelofcerebralinfarction.ThemechanismsofactionwerehypothesizedtobeassociatedwithdendriticorsynapticplasticityintheipsilateralhippocampalCA3region.
简介:目的探讨脑梗死病人血清肝细胞生长因子(Hepatocytegrowthfactor,HGF)和可溶性细胞间粘附分子(Solubleintercellularadhesionmolecule-1,sICAM-1)的水平及临床意义。方法采用双抗体酶联免疫吸附法(ELISA)测定63例脑梗死病人急性期、恢复期和25例健康对照组血清HGF、sICAM-1的水平。结果脑梗死病人急性期血清HGF、sICAM-1水平显著高于对照组(P〈0.01),且在轻、中、重型之间比较有统计学意义(P〈0.01~0.05)。在恢复期与对照组比较无显著性差异(P〉0.05)。结论脑梗死病人急性期血清HGF、sICAM-1水平升高,推测HGF作为神经营养因子参与脑梗死后脑损伤的修复,sICAM-1作为炎症/免疫因子参与了脑梗死的病理过程。血清GHF、sICAM-1水平随神经功能缺损严重程度增加而增高,可作为病情严重程度的参考指标。