简介:ThedefiningneuropathologicalfeatureofParkinson’sdisease(PD)isthelossofnigrostriataldopaminergic(DA)projections.Thisresultsinabiochemicalreductionofstriataldopaminelevelsandmovementdisorders,suchasatremoratrest,rigidityofthelimbs,bradykinesia,andposturalinstability(Kimetal.,2011;Kimetal.,2012;BurkeandO’Malley,2013;Leemetal.,2014;Nametal.,2014).BecausetheetiologyofPDisnotfullyunderstood,itcannotguidethedevelopmentofknowledge-basedtargetedtherapeutics.
简介:Parkinson’sdisease(PD)isanage-relatedneurodegenerativedisordercharacterizedbytypicalmotorsignsandsymptomsthatareduetodopamine(DA)depletioninthebasalganglia.ThetreatmentofPDissymptomatic,andaimsatreplacingthelostDAinputusingeitherL-DOPAorDAagonists.ThecausesofPDareunknownin
简介:Oxidativestressiscloselyassociatedwithsecondarycelldeathinmanydisordersofthecentralnervoussystemincludingstroke,Parkinson’sdisease,Alzheimer’sdisease.Amongmanyaberrantoxidativestress-associatedproteins,DJ-1hasbeenassociatedwiththeoxidativestresscelldeathcascadeprimarilyinParkinson’sdisease.Althoughprincipallyexpressedinthecytoplasmandnucleus,DJ-1canbesecretedintotheserumunderpathologicalcondition.Recently,aclosepathologicalassociationbetweenDJ-1andoxidativestressinstrokehasbeenimplicated.Tothisend,weandothershavedemonstratedtheimportantroleofmitochondriainneuroprotectionforstrokebydemonstratingthatthetranslocationofDJ-1inthemitochondriacouldpotentiallymitigatemitochondrialinjury.Here,wediscussourrecentfindingstestingthehypothesisthatDJ-1notonlyfunctionsasaformofintracellularprotectionfromoxidativestress,butthatitalsoutilizesparacrineand/orautocrinecuesinordertoaccomplishextracellularsignalingbetweenneighboringneuronalcells,resultinginneuroprotection.ThisarticlehighlightsrecentevidencesupportingthestatusofDJ-1askeyanti-oxidativestresstherapeutictargetforstroke.
简介:Thehippocampalregionofthebrainisimportantforencodingenvironmentinputsandmemoryformation.However,theunderlyingmechanismsareunclear.ToinvestigatethebehaviorofindividualneuronsinresponsetosomatosensoryinputsinthehippocampalCA1region,werecordedandanalyzedchangesinlocalfieldpotentialsandthefiringratesofindividualpyramidalcellsandinterneuronsduringtailclampinginurethane-anesthetizedrats.Wealsoexploredthemechanismsunderlyingtheneuronalresponses.Somatosensorystimulation,intheformoftailclamping,changedlocalfieldpotentialsintothetarhythm-dominatedwaveforms,decreasedthespikefiringofpyramidalcells,andincreasedinterneuronfiring.Inaddition,somatosensorystimulationattenuatedorthodromic-evokedpopulationspikes.TheseresultssuggestthatsomatosensorystimulationsuppressestheexcitabilityofpyramidalcellsinthehippocampalCA1region.Increasedinhibitionbylocalinterneuronsmightunderliethiseffect.Thesefindingsprovideinsightintothemechanismsofsignalprocessinginthehippocampusandsuggestthatsensorystimulationmighthavetherapeuticpotentialforbraindisordersassociatedwithneuronalhyperexcitability.
简介:患者,女,32岁,以“头颈部反复酸痛3年,伴视物模糊半年”为主诉于2013年12月3日入院,神经系统体格检查未见明显异常.入院后头颅MRI平扫示:右侧后颅窝可见1个类圆形异常信号软组织块影,大小约5.5cm×3.7cm×3.2cm,T1WI等低信号,T2WI高低混杂信号,内可见血管流空信号,未见“脑膜尾征”.磁共振扩散加权成像(diffusionweightedimaging,DWI)信号稍高,增强扫描肿块明显强化,未见明显坏死区,其后上缘宽基底与小脑幕相连,与右侧横窦分界不清,邻近小脑组织明显受推压并见水肿带,第四脑室明显受压变窄并左移,桥脑轻度受压,第三脑室及双侧侧脑室明显扩张,蝶鞍稍扩
简介:Hypoxia-induciblefactor1(HIF-1)attenuatesamyloid-betaproteinneurotoxicityanddecreasesapoptosisinducedbyoxidativestressorhypoxiaincorticalneurons.Inthisstudy,weconstructedarecombinantadeno-associatedvirus(rAAV)vectorexpressingthehumanHIF-1αgene(rAAV-HIF-1α),andtestedtheassumptionthatrAAV-HIF-1αrepresseshippocampalneuronalapoptosisinducedbyamyloid-betaprotein.OurresultsconfirmedthatrAAV-HIF-1αsignificantlyreducesapoptosisinducedbyamyloid-betaproteininprimaryculturedhippocampalneurons.DirectintracerebralrAAV-HIF-1αadministrationalsoinducedrobustandprolongedHIF-1αproductioninrathippocampus.SinglerAAV-HIF-1αadministrationresultedindecreasedapoptosisofhippocampalneuronsinanAlzheimer’sdiseaseratmodelestablishedbyintracerebroventricularinjectionofaggregatedamyloid-betaprotein(25–35).OurinvitroandinvivofindingsdemonstratethatHIF-1haspotentialforattenuatinghippocampalneuronalapoptosisinducedbyamyloid-betaprotein,andprovidesexperimentalsupportfortreatmentofneurodegenerativediseasesusinggenetherapy.
简介:目的总结颅眶沟通黏膜相关淋巴组织结外边缘区B细胞(MALT)淋巴瘤的诊治经验。方法回顾性分析l例眼眶MALT淋巴瘤原位复发及颅内、颌面部转移患者的临床资料,结合文献复习,讨沦其转移方式、影像学特点及治疗措施。结果该患者行联合手术治疗颅眶占位病变,颌面部病变未处理,术后病理学结果为MALT淋巴瘤;术后复查MRI示右侧眼眶肿瘤全切,术后2周左眼视力较术前改善。结论眼眶MALT淋巴瘤转移至颅内罕见,需于术联合放疗或化疗,术后长期随访十分重要。
简介:目的探讨脑出血后血清中IL-1β的表达水平与脑水肿变化的相关性。方法通过自体血注入法成功制作稳定的雄性高血压大鼠脑出血模型(ICH组,行为学判定异常,30只)和对照组(30只),在脑出血后8、16、24、48、72和120h采用右脑半球干湿法测定脑含水量和ELISA测定外周血血清中IL-1β含量,分析其变化规律,采用二次项非线性回归分析,了解二者相关性。结果与对照组相比,ICH组脑出血后大鼠立即出现行为学异常,但在120h已无明显差异。与对照组相比,ICH组大鼠血清IL-1β在16-72h出现明显高水平表达,脑含水量在24-72h明显增高,差异均具有统计学意义(均P〈0.05),而在120h时,两项差异已无统计学意义(均P〉0.05)。血清IL-1β表达水平与脑水肿二者变化规律存在正相关性(r=0.906,P〈0.001)。结论ICH组大鼠血清IL-1β变化趋势与脑含水量变化趋势一致,血清IL-1β可作为ICH后脑水肿程度的一个判定指标,为治疗方式选择提供依据。
简介:CurrentevidenceshowsthatapolipoproteinE(APOE),apolipoproteinCI(APOC1)andlowdensitylipoproteinreceptor-relatedprotein(LRP)variationsarerelatedtolate-onsetAlzheimer’sdisease.However,itremainsunclearifgeneticpolymorphismsinthesegenesareassociatedwithcognitivedeclineinlate-onsetAlzheimer’sdiseasepatients.Weperformeda30-monthlongitudinalcohortstudytoinvestigatetherelationshipbetweenAlzheimer’sdiseaseandAPOE,APOC1,andLRP.Inthisstudy,78ChineseHanpatientswithlate-onsetAlzheimer’sdiseasewererecruitedformGuangxiZhuangAutonomousRegioninChina.APOE,APOC1,andLRPgenotypingwasperformedusingpolymerasechainreaction-restrictionfragmentlengthpolymorphisms.TheMini-MentalStateExaminationandClinicalDementiaRatingScalewereusedtoassesspatients’cognitivefunction.Aftera30-monthfollow-upperiod,wefoundasignificantreductioninMini-MentalStateExaminationtotalscore,ahigherproportionofpatientsfulfillingcognitiveimpairmentprogressioncriteria,andahigherproportionofAPOC1H2carriersinAPOEε4carrierscomparedwithnon-carriers.Inaddition,theAPOEε4allelefrequencywassignificantlyhigherinthecognitiveimpairmentprogressiongroupcomparedwiththenon-cognitiveimpairmentprogressiongroup.Inconclusion,APOEε4playsanimportantroleinaugmentingcognitivedecline,andAPOC1H2mayactsynergisticallywithAPOEε4inincreasingtheriskofcognitivedeclineinChinesepatientswithlate-onsetAlzheimer’sdisease.