简介:HippocampalvolumelossisanimportantbiomarkerindistinguishingsubjectswithAlzheimer’sdisease(AD)anditsmeasurementinmagneticresonanceimages(MRI)isinfluencedbypartialvolumeeffects(PVE).Thispaperdescribesapost-processingapproachtoquantifyPVEforcorrectionofthehippocampalvolumebyusingaspatialfuzzyC-means(SFCM)method.Thealgorithmisevaluatedonadatasetof20T1-weightedMRIscanssampledattwodifferentresolutions.Thecorrectedvolumesforleftandrighthippocampus(HC)whichare23%and18%forthelowresolutionand6%and5%forthehighresolutiondatasets,respectivelyarelowerthanhippocampalvolumeresultsfrommanualsegmentation.ResultsshowtheimportanceofapplyingthistechniqueinADdetectionwithlowresolutiondatasets.
简介:MaleWistar7-day-oldratswereinjectedwith40mg/kgketamineintraperitoneally,followedbythreeadditionalinjectionsof20mg/kgketamineeachuponrestorationoftherightingreflex.Neonatalratsinjectedwithequivalentvolumesofsalineservedascontrols.Hippocampalsampleswerecollectedat1,7or14daysfollowingadministration.Electronmicroscopyshowedthatneuronalstructurechangednoticeablyfollowingketaminetreatment.Specifically,microtubularstructurebecameirregularanddisorganized.Quantitativerealtime-PCRrevealedthatphosphorylatedtaumRNAwasupregulatedafterketamine.Westernblotanalysisdemonstratedthatphosphorylatedtaulevelsatserine396initiallydecreasedat1dayafterketamineinjection,andthengraduallyreturnedtocontrolvalues.At14daysafterinjection,levelsofphosphorylatedtauwerehigherintheketaminegroupthaninthecontrolgroup.Tauproteinphosphorylatedatserine404significantlyincreasedafterketamineinjection,andthengraduallydecreasedwithtime.However,thelevelsoftauproteinatserine404weresignificantlygreaterintheketaminegroupthaninthecontrolgroupuntil14days.ThepresentresultsindicatethatketamineinducesanincreaseofphosphorylatedtaumRNAandexcessivephosphorylationoftauproteinatserine404,causingdisruptionofmicrotubulesintheneonatalrathippocampusandpotentiallyresultingindamagetohippocampalneurons.
简介:Electroacupuncture(EA)hasbeenclinicallyusedtotreatdepressionandhasresultedinfavorableeffectsinChina.However,resultsfromanimalstudiesandpathologydonotreflecttheinfluenceofelectroacupuncturetreatmentoninvivophysiologicalfunctions.Tothoroughlyanddynamicallyobservepathologicalchangesduringdepression,thepresentstudyestablishedEA+fluoxetineandfluoxetinegroupstoobservedepressioninpatients.1H-magneticresonancespectroscopywasutilizedtodeterminethecorrelationbetweenhippocampalfrontallobemetabolitechangesandmentaldisorderscale.ResultsrevealedsignificantlyincreasedN-acetylaspartate(NAA)/creatine(Cr)inthebilateralhippocampusandrightfrontallobeofdepressionpatientstreatedwithEAcomparedwithfluoxetine.ChangesinNAA/Crinbilateralhippocampusandrightfrontallobeinbothgroups,beforeandaftertreatment,negativelycorrelatedwithseverityandcurativeeffects.Choline/Crchangesinthebilateralfrontallobesofbothgroupsweresignificantbeforeandaftertreatment,butnegativelycorrelatedwithcurativeeffects.Choline/CrchangesinthebilateralhippocampusweresignificantintheEA+fluoxetinegroupbeforeandaftertreatment,butnegativelycorrelatedwithseverityandthecurativeeffectsofdepression.Theseresultsdemonstrateabnormalbiochemicalmetabolisminbilateralfrontallobesandhippocampusofdepressionpatients,andshowthatEAsignificantlyalteredbiochemicalindicesinthefrontallobesandhippocampuscomparedwithfluoxetine.
简介:Objective:Toinvestigateifhyperbaricoxygen(HBO)mayinducestructuralchangesofneuronsinhippocampusfrominfactileratsandifthechangesarereversible.Methods:All27healthySDinfantileratswereexposedtoHBO(0.25MPa)orhyperbaricair(HBA)for1to3courses(10daysas1course).Thehippocampuswastakenattheendofeachcoursetoobserveitsmorphologybylightmicroscopeandelectronmicroscope.Results:HBOexposureinducedcapillarydilation,nuclearmembranewindingorblurringandsomemitochondriaswellingwithitscristablurringinneurons.Thechangesoccurredafter1courseexposureandbecamesignificantwithtime.Mostofthechangesrecovered20daysafterstoppingexposure.NochangewasfoundafterHBAexposure.Conclusions:Long-termHBOexposurecancausecapillarydilationandultrastructuralinjuryofneuronsinhippocampusfrominfantilerats.Thedamageisnotserious,butreversible.
简介:BACKGROUND:ToevaluateandsummarizetheeffectsofcerebralperfusionandvascularreserveonthetreatmentofSICAS.Recently,researchonβ-amyloidproteinhasfocusedontheregulatoryeffectsofes-trogenorphytoestrogenonitsdeposition.However,therehavebeenonlyafewreportsondynamicchangesofβ-amyloidproteindepositioninhippocampusofovariectomizedrats.OBJECTIVE:Tomeasureβ-amyloidproteindepositioninthehippocampalformationofovariectomizedratsbyusingimmunohistochemistry;toobservetime-dependentdynamicchanges.DESIGN:Randomizedcontrolledanimalstudy.SETTING:ThirdXiangyaHospitalofCentralSouthUniversity.MATERIALS:TheexperimentwascarriedoutintheCentralLaboratoryoftheThirdXiangyaHospitalofCentralSouthUniversityfromNovember2005toDecember2006.FiftyhealthyfemaleSpragueDawley(SD)rats,weighing(293±10)g,wereprovidedbytheAnimalLaboratoryofXiangyaMedicalCollege,CentralSouthUniversity.Allratshadneitherachildbearinghistorynorhepaticorrenaldisease,orskeletaldeformity.β-amyloidproteinimmunohistochemicalkitwasprovidedbyWuhanBosterCompany.Theex-perimentwasinaccordancewithanimalethicsstandards.METHODS:Allratswererandomlydividedintofivegroups,includingnormalcontrolgroup(n=10),shamoperationgroup(n=10),andovariectomizedgroup(n=30).Afteranesthesiaintheovariectomizedgroup,thebilateralovarieswereseparatedandresected.Thesamevolumeoffatwasresectedintheshamoperationgroup.Ratsfromthenormalcontrolgroup,however,didnotreceiveanysurgicaltreatments.Ratsinthenormalcontrolgroupandshamoperationgroupweresacrificedbyanesthesia7weeksaftersurgery.Everytenratsfromtheovariectomizedgroupwasrespectivelysacrificedat7,15,and30weeksaftersurgery.Immunohistochemistrywasusedtodetectβ-amyloidproteindepositioninhippocampalsections.Cellcountingandgrayvaluemeasurementsservedtorecordthedynamicchangesin�
简介:ThepresentstudywasdesignedtodeterminethechangesofphosphorylationofcAMP-responseele-mentbindingprotein(CREB)inhippocampusinducedbyohmefentanylstereoisomers(F9202andF9204)inconditionedplacepreference(CPP)paradigm.TheresultsshowedthatmicereceivingF9202andF9204displayedobviousCPP.TheycouldallsignificantlystimulateCREBphosphorylationandmaintainedforalongtimewithoutaffectingtotalCREBproteinlevels.TheeffectofF9204wassimilartomorphinewhicheffectwasmorepotentandlongerthanF9202.Wealsoexaminedtheeffectsofketamine,anoncompetitiveN-mthyl-D-aspartatereceptor(NR)antagonist,onmorphine-,F9202-andF9204-inducedCPPandphos-phorylationofCREBinhippocampus.KetaminecouldsuppressnotonlytheplacepreferencebutalsothephosphorylationofCREBproducedbymorphine,F9202andF9204.ThesefindingssuggestthatalterationsinthephosphorylationofCREBberelevanttoopiatessignalingandthedevelopmentofopiatesdependence.NRantagonistsmayinterferewithopiatesdependenceandmayhavepotentialtherapeuticimplications.
简介:Therearecurrentlynofederallyapprovedneuroprotectiveagentstotreattraumaticbraininjury.Progesterone,ahydrophobicsteroidhormone,hasbeenshowninrecentstudiestoexhibitneuroprotectiveeffectsincontrolledcorticalimpactratmodels.Aktisaproteinkinaseknowntoplayaroleincellsignalingpathwaysthatreduceedema,inflammation,apoptosis,andpromotecellgrowthinthebrain.ThisstudyaimstodetermineifprogesteronemodulatesthephosphorylationofAktviaitsthreonine308phosphorylationsite.Phosphorylationatthethreonine308siteisoneofseveralsitesresponsibleforactivatingAktandenablingtheproteinkinasetocarryoutitsneuroprotectiveeffects.ToassesstheeffectsofprogesteroneonAktphosphorylation,C57BL/6miceweretreatedwithprogesterone(8mg/kg)at1(intraperitonally),6,24,and48hours(subcutaneously)postclosed-skulltraumaticbraininjury.Thehippocampuswasharvestedat72hourspostinjuryandpreparedforwesternblotanalysis.TraumaticbraininjurycausedasignificantdecreaseinAktphosphorylationcomparedtoshamoperation.However,micetreatedwithprogesteronefollowingtraumaticbraininjuryhadanincreaseinphosphorylationofAktcomparedtotraumaticbraininjuryvehicle.Ourfindingssuggestthatprogesteroneisaviabletreatmentoptionforactivatingneuroprotectivepathwaysaftertraumaticbraininjury.
简介:BACKGROUND:Anaminoacidimbalancehasbeenconsideredtoberesponsibleforepilepsypathogenesis.Gamma-aminobutyricacid-Breceptor(GABA_BR)inhibitsvoltage-sensitivecalciumionchannelsandGABAorglutamicacid(Glu)neurotransmitterrelease,whichpromotesorinhibitsonsetanddevelopmentofepilepsy.OBJECTIVE:ToexploretheeffectofbaclofenonGBR1aandGBR2mRNAexpressioninthehippocampusofepilepticratsfollowingkainicacid(KA)induction,andtostudytheadaptabilityofGABA_BRsubunits.DESIGN,TIMEANDSETTING:Arandomized,controlled,animalexperimentbasedonmolecularbiologywasperformedattheLaboratoryResearchCenterofSecondHospitalAffiliatedtoSoochowUniversityfromNovember2005toMarch2006.MATERIALS:KAwasprovidedbySigma,USA.InsituhybridizationdetectionkitofGBR1aandGBR2wasprovidedbyWuhanBosterBiologicalTechnology,China.GABA_BRagonist(baclofen)wasprovidedbySigma,USA.METHODS:Forty-fourepilepticratswererandomlyallocatedtoepileptic(n=28)anddrugintervention(n=16)groups.Theepilepticgroupwasfurtherdividedintopost-epilepticsubgroupsatdifferenttimepoints:6,12hours,1,3,7,15,and30days(n=4).Thedruginterventiongroupwasfurtherdividedintointerventioncontrolssubgroupsatvarioustimepoints:6hours,1day,and3days(n=4).Fouradditionalratswereconsideredthenormalcontrolgroupandnotmodeled,butwereinjectedwithsalineinthehippocampalCA3region.MAINOUTCOMEMEASURES:GBR1aandGBRmRNAexpressionwasdetectedintherighthippocampalCA1,CA3,anddentategyrus(DG)areasofthecontrol,epileptic,andinterferencegroupsatvarioustimeintervalsaccordingtoinsituhybridizationresults.RESULTS:(1)Duringtheearlystageofepilepsy(6and12hours),GBR1aandGBR2mRNAexpressionwasdecreased,andexpressionwaslessthanthecontrolgroupatonedayafterKAinduction(P<0.05).mRNAexpressionwasincreasedintheDG,butwasgreaterthanthecontrolgroupatday3(P<0.05).ExpressioninthehippocampalCA1andCA3regi
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简介:AbstractBackground:Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level.Methods:We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses.Results:The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance.Conclusion:Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.
简介:BACKGROUND:Argininevasopressinhasbeenshowntoenhancelearninginexperimentalanimalmodels.OBJECTIVE:TodeterminewhetherGuipidecoctionenhancesmemoryandlearningbyincreasingargininevasopressinlevels,andtoverifytheinfluenceofGuipidecoctiononargininevasopressinproteinandgeneexpressioninthehippocampalCA1region,prefrontallobecortex,andventralnucleusofhypothalamusinratswithspleendeficiency.DESIGN,TIMEANDSETTING:Therandomized,neuropharmacological,controlstudywasperformedintheCollegeofBasicMedicalSciences,BeijingUniversityofChineseMedicinebetweenMarch2002andMarch2005.MATERIALS:Sixty,healthy,male,WistarratswereusedtoestablishspleendeficiencymodelsaccordingtothetraditionalChinesemedicineprincipleofbitterdrugsforpurgation,improperdiet,andoverstrain.Argininevasopressin-1polyclonalanti-rabbitantibodyimmunohistochemistrykitandargininevasopressininsituhybridizationkitwereprovidedbyDepartmentofNeuroanatomyinShanghaiSecondMilitaryMedicalUniversityofChinesePLA.METHODS:Sixtyratsweredividedintofivegroupsatrandom:normalcontrol(n=11),model(n=13),Guipidecoction(n=12),recipecontrolA(n=12),andrecipecontrolBgroups(n=12).Ratsinthelatterfourgroupsreceived7.5g/kgofthedrugsbyintragastricadministrationeachmorning,whichcomprisedDahuang,Houpu,andZhishi,preparedataratioof2:1:1.Theratswerefastedeveryotherday,butwereallowedfreeaccesstowateratalltimes.Theratswereforcedtoswimin25℃wateruntilfatigued.RatsintheGuipidecoctionandtworecipecontrolgroupswereintragastricallyadministered7.5g/kgGuipidecoction,ChaihuShuganpowder,andTianwangBuxinpellets,respectively,eachafternoon.Ratsinthenormalgroupwereintragastricallyadministeredthesameamountofnormalsaline.Allratsweretreatedfor6weeks.MAINOUTCOMEMEASURES:At6weeksafterdrugadministration,ratbraintissueswereharvested.Ar
简介:BACKGROUND:Thestellateganglionblock(SGB)playsaprotectiveroleinfocalcerebralischemia/reperfusioninjury.ThehumanSGBcanbesimulatedbytransectionofthecervicalsympathetictrunk(TCST)inrats.OBJECTIVE:ToobservetheeffectsofTCSToninduciblenitricoxidesynthase(iNOS)levelsandcerebralinfarctvolumeinthehippocampusofratswithcerebralischemia/reperfusioninjury,andtoanalyzethemechanismofaction.DESIGN,TIMEANDSETTING:Acompletelyrandomized,controlled,neuropathologicalexperimentwasperformedattheInstituteofNeurologicalDisease,TaiheHospital,YunyangMedicalCollegebetweenMarchandSeptember2006.MATERIALS:Atotalof93Wistarrats,aged17-18weeks,ofeithergender,wereusedforthisstudy.2,3,5-triphenyltetrazoliumchloridewaspurchasedfromChangshaHongyuanBiologicalReagentCompany,China.RabbitiNOSantibodyandgoatanti-rabbitIgGantibodyweretheproductsofWuhanBosterBiologicalReagentCo.,Ltd.,China.METHODS:Tenratswererandomlyselectedforthesham-operatedgroup.Cerebralischemia/reperfusioninjurywasinducedbymiddlecerebralarteryocclusion(MCAO)usingthesuturemethodintheremainingrats.Fortysuccessfulratmodelswererandomlyandequallydividedintothefollowingtwogroups:(1)TCSTgroup:subsequenttoTCST,MCAOwasperformedfor2hours,followedby24hoursreperfusion;(2)modelgroup:ratsunderwentexperimentalproceduressimilartotheTCSTgroup,withtheexceptionofTCST.Ratsinthesham-operatedgroupweresubjectedtoexperimentalproceduressimilartothemodelgroup;however,thethreadwasonlyintroducedtoadepthof10mm.MAINOUTCOMEMEASURES:Following24hoursofreperfusion,functionalneurologicaldeficitswerescored.BraintissuesectionsfromtenratsofeachgroupwereusedtomeasurecerebralinfarctvolumebyTTCstaining.HippocampaltissuesectionsofanadditionaltenratsfromeachgroupwereusedtodetectiNOSlevelsusingthestreptavidin-peroxidaseimmunohistochemis
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