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1.
髓鞘修复与多发性硬化 总被引:1,自引:0,他引:1
多发性硬化(MS)是以中枢神经系统炎性脱髓鞘为特征的自身免疫性疾病,神经功能障碍与髓鞘和轴索损伤有关。MS动物模型研究认为:髓鞘修复是治疗MS极有前景的途径。中枢神经系统存在少突胶质细胞前体细胞(OPCs),在髓鞘修复和再生过程起关键作用。由于MS病人OPC分化受抑制,因此,在髓鞘再生过程中调控OPCs分化是髓鞘修复的重点。另外,移植外源性的髓鞘形成细胞促进髓鞘修复和神经再生,是修复MS脱髓鞘和轴索损伤的重要途径。 相似文献
2.
本研究通过在饲料中掺入cuprizone饲育小鼠,建立髓鞘可再生的急性脱髓动物模型,并利用髓鞘染色和原位杂交后免疫组化双标技术,检测髓鞘脱失和再生状况以及少突胶质前体细胞的改变。结果表明,给予cuprizone6周后,动物胼胝体严重脱髓鞘,少突胶质前体细胞在髓鞘脱失区域集聚,且增殖活跃;恢复正常饲料饲养4周后,髓鞘基本恢复正常形态。由此推测,在cuprizone介导的急性脱髓动物模型髓鞘脱失和再生过程中,少突胶质前体细胞的增殖活化为髓鞘再生提供了基础。 相似文献
3.
目的:评价喹硫平治疗中国精神分裂症患者急性期兴奋激越的疗效和安全性.方法:本研究为多中心随机对照研究.选取80例符合国际疾病与相关健康问题分类第十版(ICD-10)精神分裂症诊断标准并处于急性兴奋激越状态的患者,按1∶1随机分为喹硫平组(n=40)和氟哌啶醇组(n=40),接受28天的喹硫平或氟哌啶醇治疗.入组时和治疗第1、3、7、10、14、28天进行临床评估,采用阳性与阴性症状量表(PANSS)和总体印象量表中的疾病严重程度(CGI-SI)评估临床症状,并采用PANSS兴奋因子(PANSS-EC)的减分值以及起效时间(PANSS-EC减分率达20%的时间)为主要疗效指标,Simpson-Angus类帕金森综合征量表(SAS)评定锥体外系不良反应.每次临床评估时记录生命体征和服药情况,基线和治疗第28天进行体格检查及血、尿、血生化常规,血清催乳素,心电图等实验室检查.结果:治疗第28天,喹硫平组剂量为(672.9±88.3)mg,氟哌啶醇组剂量为(11.5±3.2)mg.喹硫平组和氟哌啶醇组PANSS-EC评分随着治疗时间的延长逐渐降低,治疗第1天两组均12.5%起效,治疗第7天起效率分别达到82.5%和75.0%.治疗第28天,两组PANSS、CGI-SI量表得分差异无统计学意义,喹硫平组的不良事件发生率(40.0% vs.87.5%)、SAS评分[(0.2±0.8)vs.(1.5±2.2)]和泌乳素水平[(375.0±388.2) μIU/mL vs.(1526.5 ±1300.6) μIU/mL]均低于氟哌啶醇组(均P<0.05).喹硫平组的心电图QT间期治疗前后无明显变化,氟哌啶醇组则从(351.8 ±46.1) ms增加至(374.3±27.5) ms(P<0.05).结论:喹硫平单药治疗精神分裂症急性期兴奋激越症状起效快速、疗效充分,安全性高、耐受性好. 相似文献
4.
Olig对少突胶质细胞介导脱髓鞘大鼠髓鞘再生的影响 总被引:1,自引:1,他引:0
目的 探讨Olig在少突胶质细胞介导的脱髓鞘大鼠髓鞘再生中的作用。方法 40只健康Wistar大鼠,随机分成正常组、模型对照组、模型组、实验组,用形态学观察和免疫组织化学检测Olig1和Olig2的表达。结果 正常组Olig1位于少突胶质细胞的胞质,模型组胞核表达明显增多,实验组Oligl又重新转移至胞质;正常组Olig2表达位于胞核,模型组中有少量表达于胞质。 结论 在Olig1和Olig2同时缺失时,导致全脑不能形成少突胶质细胞,严重影响髓鞘的再生。 相似文献
5.
目的观察喹硫平和氟哌啶醇治疗老年痴呆精神行为症状的疗效和安全性。方法采用随机对照研究,喹硫平组36例,剂量(140±50)mg/d,氟哌啶醇组33例,剂量(4.5±1.5)mg/d,疗程12周,治疗前后采用痴呆病理分析评定量表(BEHAVE-AD)、Cohen-Mansfied激越问卷(CMAI)评定疗效,用副反应量表(TESS)评定不良反应。结果两组病人治疗后BEHAVE-AD评分显著下降(P0.01),两组病人之间治疗前后BEHAVE-AD的减分值无显著差异(P0.05),氟哌啶醇组38%有锥体外系反应,明显高于喹硫平组的3%,并有显著差异(P0.05)。结论喹硫平和氟哌啶醇治疗老年痴呆精神行为症状疗效确切,喹硫平不良反应少。 相似文献
6.
BMP-4在视网膜与视神经中的分布及对少突胶质前体细胞分化的影响 总被引:1,自引:0,他引:1
目的:研究骨形态发生蛋白4(bone morphogenetic protein4,BMP-4)在视网膜与视神经上的表达情况及其对少突胶质前体细胞(oligodendrocyte precursor cells,OPCs)分化的影响,进一步探讨视神经乳头处无髓鞘形成的原因。方法:取生后7d SD大鼠视神经,用免疫组织化学方法研究BMP-4的表达情况。采用恒温振荡法和差速贴壁法分离纯化新生SD大鼠OPCs。用BMP-4诱导OPCs分化,通过免疫细胞化学方法研究OPCs的分化方向。通过Western Blot方法研究BMP-4浓度与OPCs细胞体系内Olig2蛋白表达水平之间的相互关系。结果:(1)在发育过程中,BMP-4仅选择性表达在视神经乳头处;(2)成功纯化的OPCs在PDGF和bFGF撤除后自发分化为少突胶质细胞;(3)OPCs经BMP-4诱导后向II型星形胶质细胞分化;(4)OPCs内Olig2蛋白的表达量随着BMP-4浓度的逐渐增高而逐渐降低。结论:在视神经乳头表达的BMP-4蛋白有可能作用于迁移至此处的OPCs,通过激活相关信号途径以下调OPCs内Olig2蛋白的表达水平,抑制OPCs向少突胶质细胞方向分化,从而抑制视神经乳头髓鞘形成。 相似文献
7.
目的观察肝脏X受体非选择性激动剂TO901317对酒精致新生小鼠大脑白质内炎症反应的调节作用。方法分别采用少突胶质前体细胞标记物血小板源性生长因子受体α(PDGFR-α),星形胶质细胞标记酸性纤维胶原蛋白(glial fibrillary acidprotein,GFAP),小胶质细胞标记物(tomato-lectin),运用免疫组织化学方法检测LXR激动剂TO901317对出生后第6天(P6)酒精致小鼠大脑胼胝体处白质炎症反应的作用及少突胶质前体细胞的调节作用。结果新生小鼠(P5)酒精暴露使脑白质处PDGFR-标记的少突胶质前体细胞数量显著减少(P<0.01),而GFAP标记的星形胶质细胞数量和tomato-lectin标记的小胶质细胞数量显著增加(P<0.01),TO901317预处理导致酒精暴露新生小鼠大脑白质PDGFR-α阳性细胞数量明显高于单纯酒精注射组(P<0.01),而GFAP,tomato-lectin阳性细胞数量明显低于单纯酒精注射组(P<0.01)。结论 LXR受体激活能有效抑制大脑白质神经炎症反应,并促进少突胶质前体细胞存活。 相似文献
8.
背景:髓鞘蛋白是少突胶质细胞的主要成分,研究脑缺血再灌注后大脑髓鞘相关蛋白基因表达的变化有助于探讨少突胶质前体细胞在缺血性脑损伤和修复中的作用。
目的:观察脑缺血再灌注后成年模型大鼠大脑髓鞘蛋白相关基因,在脑缺血后不同时间及部位表达变化和差异。
方法:以线栓法制作成年SD大鼠局灶性脑缺血再灌注模型,采用5′末端标记地高辛的寡核苷酸探针荧光原位核酸分子杂交检测模型大鼠再灌注后早期大脑梗死中心区、梗死周边区和梗死对侧区皮质髓鞘蛋白脂质蛋白mRNA、髓鞘碱性蛋白mRNA和髓鞘转录因子1 mRNA表达变化。
结果与结论:在梗死中心区,脑缺血再灌注后早期3种髓鞘相关蛋白基因表达均明显减少;在梗死周边区,再灌注后1 d时3种髓鞘相关蛋白基因表达与对照组比较无明显变化,之后逐渐增加,至14 d时均高于对照组(P < 0.05,0.01),以髓鞘转录因子1 mRNA阳性细胞数升高最早(7 d)最为显著(P < 0.01)。因此,成年SD大鼠脑缺血再灌注后急性期梗死周边区皮质髓鞘相关蛋白的基因表达增加,提示少突胶质前体细胞对脑缺血性损伤敏感,其可能参与了脑缺血后损伤的修复过程。 相似文献
9.
目的:分析地塞米松对实验性自身免疫性脑脊髓炎(EAE)小鼠炎症反应、髓鞘脱失及髓鞘再生的影响,探讨地塞米松治疗多发性硬化的新作用。方法:应用MOG35-55免疫C57BL/6小鼠建立EAE模型。小鼠随机分为正常对照组、EAE组及地塞米松组,观察各组临床症状;采用HE染色、LFB染色、透射电镜扫描及免疫组化染色方法,检测免疫后第13、20、30 d各组小鼠脊髓组织炎症反应、髓鞘脱失及髓鞘再生情况。结果:地塞米松显著降低EAE小鼠发病率、延缓起病时间、减轻疾病严重程度。各个时间点地塞米松组脊髓组织炎性细胞浸润、髓鞘脱失及轴索变性程度较EAE组明显减轻。免疫后第20、30 d,EAE组Olig2阳性细胞数较正常对照组明显增加;免疫后各时间点,地塞米松组Olig2阳性细胞数较正常对照组均明显增加,第13、20 d较EAE组明显增加。结论:地塞米松可增加脊髓组织Olig2表达、促进髓鞘再生,这可能为地塞米松治疗EAE及多发性硬化的效应途径。 相似文献
10.
目的:研究缺血缺氧性脑损伤(HIBI)模型小鼠少突胶质前体细胞(OPCs)中磷酸化谷氨酸受体2[p-GluR2(S880)]表达变化。方法:利用右侧颈总动脉结扎并缺氧90 min方法建立C57BL/6新生小鼠HIBI模型,采用高架十字迷宫和旷场实验评估小鼠的焦虑样行为,通过免疫荧光方法检测HIBI模型小鼠脑组织中p-GluR2(S880)、少突胶质细胞标记物4(O4)和髓鞘碱性蛋白(MBP)的表达变化,用Western Blot检测p-GluR2(S880)和MBP的表达水平。结果:与假手术组相比,HIBI术后90 d小鼠有显著的焦虑样行为(P<0.05);MBP蛋白表达在HIBI术后14及28 d组明显减少;p-GluR2(S880)蛋白表达在HIBI术后各个时间点表达上调(P<0.05),HIBI组小鼠脑组织中O4与p-GluR2(S880)共标的阳性细胞数目显著升高(P<0.05)。结论:OPCs中p-GluR2(S880)表达上调可能导致HIBI模型小鼠成髓鞘障碍。 相似文献
11.
Friederike Pfeiffer Gabriele Frommer‐Kaestle Petra Fallier‐Becker 《Brain pathology (Zurich, Switzerland)》2019,29(5):675-692
Multiple Sclerosis is an autoimmune disorder causing neurodegeneration mostly in young adults. Thereby, myelin is lost in the inflammatory lesions leaving unmyelinated axons at a high risk to degenerate. Oligodendrocyte precursor cells maintain their regenerative capacity into adulthood and are able to remyelinate axons if they are properly activated and differentiate. Neuronal activity influences the success of myelination indicating a close interplay between neurons and oligodendroglia. The myelination profile determines the distribution of voltage‐gated ion channels along the axon. Here, we analyze the distribution of the sodium channel subunit Nav1.6 and the ultrastructure of axons after cuprizone‐induced demyelination in transgenic mice expressing GFP in oligodendroglial cells. Using this mouse model, we found an increased number of GFP‐expressing oligodendroglial cells compared to untreated mice. Analyzing the axons, we found an increase in the number of nodes of Ranvier in mice that had received cuprizone. Furthermore, we found an enhanced portion of unmyelinated axons showing vesicles in the cytoplasm. These vesicles were labeled with VGlut1, indicating that they are involved in axonal signaling. Our results highlight the flexibility of axons towards changes in the glial compartment and depict the structural changes they undergo upon myelin removal. These findings might be considered if searching for new neuroprotective therapies that aim at blocking neuronal activity in order to avoid interfering with the process of remyelination. 相似文献
12.
Vrushali Mangale Laura L. McIntyre Craig M. Walsh Jeanne F. Loring Thomas E. Lane 《Developmental dynamics》2019,248(1):43-52
Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by chronic neuroinflammation, demyelination, and axonal damage. Infiltration of activated lymphocytes and myeloid cells are thought to be primarily responsible for white matter damage and axonopathy. Several United States Food and Drug Administration-approved therapies exist that impede activated lymphocytes from entering the CNS thereby limiting new lesion formation in patients with relapse-remitting forms of MS. However, a significant challenge within the field of MS research is to develop effective and sustained therapies that allow for axonal protection and remyelination. In recent years, there has been increasing evidence that some kinds of stem cells and their derivatives seem to be able to mute neuroinflammation as well as promote remyelination and axonal integrity. Intracranial infection of mice with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in immune-mediated demyelination and axonopathy, making this an excellent model to interrogate the therapeutic potential of stem cell derivatives in evoking remyelination. This review provides a succinct overview of our recent findings using intraspinal injection of mouse CNS neural progenitor cells and human neural precursors into JHMV-infected mice. JHMV-infected mice receiving these cells display extensive remyelination associated with axonal sparing. In addition, we discuss possible mechanisms associated with sustained clinical recovery. Developmental Dynamics 248:43–52, 2019. © 2018 Wiley Periodicals, Inc. 相似文献
13.
The mammalian adult central nervous system (CNS) is known to respond rapidly to demyelinating insults by regenerating oligodendrocytes for remyelination from a dividing precursor population. A widespread population of cells exists within the adult CNS that is thought to belong to the oligodendrocyte lineage, but which do not express proteins characteristic of mature myelinating oligodendrocytes, such as myelin basic protein (MBP) and 2,3-cyclic nucleotide 3-phosphodiesterase (CNP). Instead, these cells have phenotypic characteristics of a more immature stage of the oligodendrocyte lineage. They express the NG2 chondroitin sulphate proteoglycan, in addition to O4 and the platelet-derived growth factor alpha-receptor, all widely accepted as markers for oligodendrocyte progenitor cells (OPCs) throughout development. However, NG2+ cells residing in the adult CNS do not resemble embryonic or neonatal NG2+ cells in terms of their morphology or proliferation characteristics, but instead represent a unique type of glial cell that has the ability to react rapidly to CNS damage. In this review, we present the evidence that adult NG2+ cells are part of the oligodendrocyte lineage and are capable of giving rise to new oligodendrocytes under both normal and demyelinating conditions. We also review the literature that these cells may have multiple functional roles within the adult CNS, notwithstanding their primary role as OPCs. 相似文献
14.
Agnes E. Nystad Stig Wergeland Lage Aksnes Kjell‐Morten Myhr Lars Bø Øivind Torkildsen 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2014,122(12):1178-1186
Vitamin D supplementation is increasingly recommended to patients with multiple sclerosis (MS). To study the effect of high‐dose vitamin D on remyelination, female C57Bl/6 mice were demyelinated with dietary 0.2% cuprizone for 7 weeks. The mice received intraperitoneal injections of 1.25‐dihydroxyvitamin D3 (calcitriol) or placebo (vehicle) injections twice a week, from week 6, throughout week 9. Mice that received calcitriol had initially increased demyelination (p = 0.021), astrocytosis (p = 0.043), and microglia activation. However, levels of astrocytosis and microglia activation dropped below those of the placebo group during the remyelination phase. There was a significant increase in myelination in the calcitriol group throughout the remyelination phase (p = 0.041), while the remyelination in the placebo group was not significant (p = 0.317). After 3 weeks of remyelination, the calcitriol group had more myelin than the placebo group (p = 0.001). The calcitriol group had a higher density of NOGO‐A positive cells throughout the remyelination phase, and the number of NOGO‐A positive cells was significantly higher in the calcitriol group at one week of remyelination (p = 0.019). There were no significant differences in extent of T‐lymphocyte infiltration. High‐dose calcitriol seems to be safe regarding remyelination. Our results indicate that this treatment could actually promote the repair process, possibly through a stimulating effect on oligodendrocyte maturation and astrocyte activation. The potential of calcitriol to stimulate the remyelination process should be investigated further in functional studies. 相似文献
15.
Merkler D Boretius S Stadelmann C Ernsting T Michaelis T Frahm J Brück W 《NMR in biomedicine》2005,18(6):395-403
Although magnetic resonance imaging (MRI) represents the most sensitive tool for the detection of white matter abnormalities in patients with multiple sclerosis (MS), the heterogeneity of MS placques severely hampers the elucidation of specific pathophysiological processes. In order to identify putative MRI markers for de- and remyelination, we employed the cuprizone mouse model which leads to a selective and reversible demyelination of the corpus callosum with little or no axonal damage. Apart from histopathology, animals were studied with high-resolution three-dimensional MRI in vivo using multiple contrasts. While individual MRI findings significantly correlated with electron microscopy, the differentiation of regions with normal, demyelinated or remyelinated white matter by one contrast alone was less specific than by histology or electron microscopy. However, an accurate MRI prediction of the in vivo myelin status was achieved by a discriminant function analysis using a combination of T1, T2 and magnetization transfer contrast. With a correct assignment of 95% of all animals examined, the procedure will allow for the survey of new therapeutic approaches aiming at improved remyelination. 相似文献
16.
目的:探讨补阳还五汤(BYHWD)灌胃联合神经干细胞(NSCs)移植对脊髓损伤(SCI)后髓鞘再生的影响.方法:将48只成年雌性SD大鼠随机分为脊髓损伤(SCI)组、BYHWD灌胃组、NSCs移植组、NSCs移植联合BYHWD灌胃(BYHWD+ NSCs)组.SCI组不做治疗;NSCs组于脊髓横断后局部移植NSCs; BYHWD+ NSCs组移植NSCs,并每天BYHWD灌胃;各组在损伤后14、28 d后分别留取损伤脊髓标本,用免疫荧光双标法检测髓磷脂碱性蛋白(MBP)表达情况,透射电镜观察脊髓白质内髓鞘超微结构变化.结果:BYHWD+ NSCs组MBP阳性表达最多,较其他3组差异有统计学意义.电镜下BYHWD+NSCs组髓鞘结构较为规整,轴突微丝、微管排列有序,线粒体结构完整,可见薄髓的再生髓鞘.结论:SCI后BYHWD灌胃联合NSCs移植能够促进损伤脊髓MBP的表达及脱髓的轴突再髓鞘化. 相似文献
17.
目的:探讨在低氧条件下,腺苷受体A2b(A2bAR)拮抗剂PSB603对少突胶质前体细胞(OPC)增殖和分化的影响。方法:剥离新生2 d SD大鼠的脑皮层,并原代培养其OPC,随机分为对照组、PSB603组、2%O_2组和实验组,实验组在2%O_2干预的基础上再给予PSB603处理,4 d后用BrdU掺入技术和免疫细胞化学方法检测BrdU阳性细胞百分数和CNPase阳性细胞百分数的变化,并用qRT-PCR技术检测各组细胞P21cip1、P27kip1 mRNA含量的变化。结果:与对照组相比较,2%O_2组的BrdU阳性细胞百分数显著上升(P0.01),P21、P27 mRNA含量均显著下调(P0.01),各组间CNPase阳性细胞百分数无明显变化;实验组与2%O_2组间各实验差异均无统计学意义(P0.05)。结论:低氧短时间干预能够促进OPC细胞的增殖,P21cip1和P27kip1参与其调控,A2b AR未改变低氧所诱导的OPC增殖。 相似文献
18.
Giampaolo Leoni Marcus Rattray Daniel Fulton Andrea Rivera Arthur M. Butt 《Journal of anatomy》2014,224(2):216-227
Expression of the transmembrane NG2 chondroitin sulphate proteoglycan (CSPG) defines a distinct population of NG2‐glia. NG2‐glia serve as a regenerative pool of oligodendrocyte progenitor cells in the adult central nervous system (CNS), which is important for demyelinating diseases such as multiple sclerosis, and are a major component of the glial scar that inhibits axon regeneration after CNS injury. In addition, NG2‐glia form unique neuron–glial synapses with unresolved functions. However, to date it has proven difficult to study the importance of NG2‐glia in any of these functions using conventional transgenic NG2 ‘knockout’ mice. To overcome this, we aimed to determine whether NG2‐glia can be targeted using an immunotoxin approach. We demonstrate that incubation in primary anti‐NG2 antibody in combination with secondary saporin‐conjugated antibody selectively kills NG2‐expressing cells in vitro. In addition, we provide evidence that the same protocol induces the loss of NG2‐glia without affecting astrocyte or neuronal numbers in cerebellar brain slices from postnatal mice. This study shows that targeting the NG2 CSPG with immunotoxins is an effective and selective means for killing NG2‐glia, which has important implications for studying the functions of these enigmatic cells both in the normal CNS, and in demyelination and degeneration. 相似文献
19.
目的:利用连二亚硫酸钠(Na2S2O4)建立少突胶质前体细胞(oligodendrocyte precursor cells,OPCs)低糖缺氧损伤模型。方法:取新生1 d Sprague-Dawley(SD)大鼠大脑皮质,体外混合及纯化培养获得OPCs,O4免疫荧光染色鉴定;取纯化2 d的OPCs,分为正常组和Na2S2O4损伤组,Na2S2O4损伤组又分为0.5、1 h和1.5 h三组,倒置显微镜下观察各组细胞形态;CCK-8法检测细胞存活率;透射电镜观察细胞超微结构。结果:免疫荧光染色鉴定显示纯化的细胞绝大部分为O4阳性;形态学观察显示,缺氧0.5 h,大部分细胞突起回缩,胞体变圆,颜色变暗,随低糖缺氧损伤时间的延长OPCs逐渐脱壁,1.5 h时只有少数贴壁细胞;CCK-8法检测显示损伤0.5、1 h和1.5 h组细胞的存活率显著降低,与正常组比较均有统计学意义,损伤后1.5 h与0.5 h比较,细胞的存活率具有显著性差异;电镜观察损伤1.5 h后的细胞,线粒体肿胀,有些细胞胞核固缩成块,细胞器破碎。结论:用浓度为2mmol/L Na2S2O4的低糖培养基处理OPCs 1.5 h可以建立有效的低糖缺氧损伤模型。 相似文献
20.
目的探讨骨髓间充质干细胞(MSCs)对体外培养的神经干细胞(NSCs)向少突胶质细胞分化的影响。方法以密度梯度离心的方法获得人hMSCs,设立3个实验组,分别是hMSCs+NSCs共培养组、hMSCs条件培养基+NSCs组、NSCs自发分化组(对照组)。通过免疫细胞化学染色及RT-PCR等手段检测不同组中NSCs向少突胶质细胞分化的情况,并探讨其可能的机制。结果与自发分化组相比,共培养组及hMSCs条件培养基作用组NSCs向少突胶质细胞分化的百分率分别为(61.3±5.7)%和(58.4±6.2)%,差异均具有显著性(<0.05);且RT-PCR结果显示,共培养组及hMSCs条件培养基作用组少突胶质细胞相关基因Olig1、Olig2的表达增强。结论 hMSCs促进体外培养的NSCs向少突胶质细胞分化,可能与hMSCs分泌可溶性因子相关。 相似文献