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Inhibiting endogenous tissue plasminogen activator enhanced neuronal apoptosis and axonal injury after traumatic brain injury 预览
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作者 Jun-Jie Zhao Zun-Wei Liu +4 位作者 Bo Wang Ting-Qin Huang Dan Guo Yong-Lin Zhao Jin-Ning Song 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期667-675,共9页
Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumat... Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumatic brain injury was established by weight-drop method.The tissue plasminogen activator inhibitor neuroserpin(5μL,0.25 mg/mL)was injected into the lateral ventricle.Neurological function was assessed by neurological severity score.Neuronal and axonal injuries were assessed by hematoxylin-eosin staining and Bielschowsky silver staining.Protein level of endogenous tissue plasminogen activator was analyzed by western blot assay.Apoptotic marker cleaved caspase-3,neuronal marker neurofilament light chain,astrocyte marker glial fibrillary acidic protein and microglial marker Iba-1 were analyzed by immunohistochemical staining.Apoptotic cell types were detected by immunofluorescence double labeling.Apoptotic cells in the damaged cortex were detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling staining.Degenerating neurons in the damaged cortex were detected by Fluoro-Jade B staining.Expression of tissue plasminogen activator was increased at 6 hours,and peaked at 3 days after traumatic brain injury.Neuronal apoptosis and axonal injury were detected after traumatic brain injury.Moreover,neuroserpin enhanced neuronal apoptosis,neuronal injury and axonal injury,and activated microglia and astrocytes.Neuroserpin further deteriorated neurobehavioral function in rats with traumatic brain injury.Our findings confirm that inhibition of endogenous tissue plasminogen activator aggravates neuronal apoptosis and axonal injury after traumatic brain injury,and activates microglia and astrocytes.This study was approved by the Biomedical Ethics Committee of Animal Experiments of Shaanxi Province of China in June 2015. 展开更多
关键词 apoptosis ASTROCYTES AXONAL INJURY inflammation microglia nerve REGENERATION neural REGENERATION neuronal INJURY neurons NEUROSERPIN tissue PLASMINOGEN activator traumatic brain INJURY
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星形胶质细胞与帕金森病相关基因的研究进展 预览
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作者 钟侦 吕钱坤(综述) 黄卫(审校) 《中风与神经疾病杂志》 CAS 2020年第2期184-186,共3页
帕金森病(Parkinson’s disease,PD)是一种患病率随年龄增长而增加的神经系统变性疾病,约影响65岁以上人群的1%。帕金森病病因在大多数患者中仍然未知,但目前普遍认为与环境、遗传和年龄等因素相关,其中遗传因素在疾病的发展进程中起重... 帕金森病(Parkinson’s disease,PD)是一种患病率随年龄增长而增加的神经系统变性疾病,约影响65岁以上人群的1%。帕金森病病因在大多数患者中仍然未知,但目前普遍认为与环境、遗传和年龄等因素相关,其中遗传因素在疾病的发展进程中起重要作用。星形胶质细胞(AS)是重要的神经胶质细胞,广泛参与了中枢神经系统(CNS)的功能发育,其功能障碍将会导致一系列神经系统变性疾病,包括PD;近些年许多研究证据表明,星形胶质细胞与帕金森病相关基因有关;由于部分基因参与调控星形胶质细胞的病理,这些基因的突变可能改变星形胶质细胞的功能,从而有助于帕金森病的发生和发展。因此,本文就星形胶质细胞与这些帕金森病相关基因的相关性作一综述。 展开更多
关键词 星形胶质细胞 帕金森病 帕金森病相关基因
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高糖下神经元及星形胶质细胞变化导致脑葡萄糖代谢改变研究进展 预览
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作者 彭婉舒 冯伟 +1 位作者 王戈 张延军 《中国医学影像技术》 CSCD 北大核心 2020年第1期138-141,共4页
糖尿病为临床常见代谢性疾病,可影响心脑血管、眼、肾等多种脏器。糖尿病相关认知减退临床表现隐匿,诊断困难。18 F-FDG PET/CT具有早期识别代谢变化的能力,广泛用于诊断神经系统疾病,可评估糖尿病患者脑葡萄糖代谢异常改变。神经元和... 糖尿病为临床常见代谢性疾病,可影响心脑血管、眼、肾等多种脏器。糖尿病相关认知减退临床表现隐匿,诊断困难。18 F-FDG PET/CT具有早期识别代谢变化的能力,广泛用于诊断神经系统疾病,可评估糖尿病患者脑葡萄糖代谢异常改变。神经元和星形胶质细胞与脑葡萄糖代谢紧密相关,其数量、功能及代谢活性等异常改变可致糖尿病认知功能减退。本文对高糖环境神经元及星形胶质细胞代谢改变对脑葡萄糖代谢的影响进行综述,分析糖尿病脑葡萄糖代谢改变的原因,以期为诊断糖尿病相关神经系统疾病提供理论依据。 展开更多
关键词 糖尿病 葡萄糖代谢障碍 神经元 星形胶质细胞
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红花黄色素调控p38MAPK对H2O2诱导的星形胶质细胞损伤的保护作用
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作者 赵红领 李磊 +1 位作者 杨慧 苗成 《免疫学杂志》 CAS CSCD 北大核心 2020年第1期80-85,共6页
目的中药红花具有悠久的神经保护应用历史,近代研究发现,红花黄色素也具有保护神经作用,但其发挥作用的机制尚未清楚。因此,研究红花黄色素对H 2 O 2诱导的星形胶质细胞氧化应激和凋亡的影响并探讨其机制。方法运用H 2 O 2诱导建立星形... 目的中药红花具有悠久的神经保护应用历史,近代研究发现,红花黄色素也具有保护神经作用,但其发挥作用的机制尚未清楚。因此,研究红花黄色素对H 2 O 2诱导的星形胶质细胞氧化应激和凋亡的影响并探讨其机制。方法运用H 2 O 2诱导建立星形胶质细胞HAs的损伤模型;用红花黄色素(10、50、100 mg/L)治疗损伤细胞;用ELISA检测细胞的LDH、SOD、GSH-PX、MDA含量;MTT法检测细胞活性;Western blot检测细胞中Bax、Bcl-2、Caspase-3、p-p38、T-p38MAPK的蛋白表达;流式细胞术检测细胞的凋亡率。结果成功构建H 2 O 2诱导的星形胶质细胞HAs损伤模型;与H 2 O 2组相比,红花黄色素(10、50、100 mg/L)治疗组细胞中LDH、MDA均显著降低,SOD、GSH-PX均显著升高,细胞活性均显著降低,细胞凋亡率均显著降低,Bcl-2蛋白表达显著升高,Bax、Caspase-3、p-p38蛋白表达均显著降低(P<0.05),且此种影响随与红花黄色素呈浓度依赖性。结论红花黄色素可保护H 2 O 2诱导建立星形胶质细胞损伤,将可为红花黄色素的临床应用提供支持。 展开更多
关键词 红花黄色素 星形胶质细胞 P38MAPK信号通路 氧化应激 细胞生长
干扰或过表达PDIA3对过氧化氢诱导的星形胶质细胞损伤的影响 预览
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作者 雷雨广 徐继鹏 +1 位作者 陈超 张伟丽 《中国老年学杂志》 CAS 北大核心 2020年第3期585-589,共5页
目的探讨干扰或过表达蛋白质二硫键异构酶(PDI)A3对过氧化氢诱导的星形胶质细胞损伤的影响及其作用机制。方法体外培养星形胶质细胞,构建PDIA3干扰及过表达载体稳定株系,采用过氧化氢(H 2O 2)诱导建立星形胶质细胞损伤模型。实验将星形... 目的探讨干扰或过表达蛋白质二硫键异构酶(PDI)A3对过氧化氢诱导的星形胶质细胞损伤的影响及其作用机制。方法体外培养星形胶质细胞,构建PDIA3干扰及过表达载体稳定株系,采用过氧化氢(H 2O 2)诱导建立星形胶质细胞损伤模型。实验将星形胶质细胞分为对照组(NC组)、H 2O 2组、H 2O 2+si-con组、H 2O 2+si-PDIA3组、H 2O 2+pcDNA组、H 2O 2+pcDNA-PDIA3组。实时荧光定量-聚合酶链反应(qRT-PCR)检测PDIA3 mRNA表达;Western印迹检测PDIA3及p38丝裂原活化蛋白激酶(p38MAPK)信号通路蛋白表达;噻唑蓝(MTT)法检测细胞活力;流式细胞术检测细胞凋亡。收集各组星形胶质培养基上清液检测细胞乳酸脱氢酶(LDH)释放率及肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6水平。结果与NC组相比,H 2O 2组星形胶质细胞中PDIA3 mRNA及蛋白表达水平均显著升高(P<0.05);H 2O 2组细胞LDH释放量、TNF-α、IL-6水平、细胞凋亡率及p-p38蛋白表达均显著升高(P<0.05),干扰PDIA3表达后明显升高(P<0.05),PDIA3过表达后明显降低(P<0.05);H 2O 2组细胞存活率显著降低(P<0.05),干扰PDIA3表达后明显降低(P<0.05),PDIA3过表达后明显升高(P<0.05)。结论PDIA3过表达可改善H 2O 2诱导的星形胶质细胞氧化应激及炎症损伤,其可能通过抑制p38MAPK信号通路激活而发挥作用。 展开更多
关键词 蛋白质二硫键异构酶A3 星形胶质细胞 p38丝裂原活化蛋白激酶(MAPK)信号通路 氧化损伤
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Regional brain susceptibility to neurodegeneration:what is the role of glial cells? 预览
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作者 Andrea Beatriz Cragnolini Giorgia Lampitella +4 位作者 Assunta Virtuoso Immacolata Viscovo Fivos Panetsos Michele Papa Giovanni Cirillo 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期838-842,共5页
The main pathological feature of the neurodegenerative diseases is represented by neuronal death that represents the final step of a cascade of adverse/hostile events.Early in the neurodegenerative process,glial cells... The main pathological feature of the neurodegenerative diseases is represented by neuronal death that represents the final step of a cascade of adverse/hostile events.Early in the neurodegenerative process,glial cells (including astrocytes,microglial cells,and oligodendrocytes) activate and trigger an insidious neuroinflammatory reaction,metabolic decay,blood brain barrier dysfunction and energy impairment,boosting neuronal death.How these mechanisms might induce selective neuronal death in specific brain areas are far from being elucidated.The last two decades of neurobiological studies have provided evidence of the main role of glial cells in most of the processes of the central nervous system,from development to synaptogenesis,neuronal homeostasis and integration into,highly specific neuro-glial networks.In this mini-review,we moved from in vitro and in vivo models of neurodegeneration to analyze the putative role of glial cells in the early mechanisms of neurodegeneration.We report changes of transcriptional,genetic,morphological,and metabolic activity in astrocytes and microglial cells in specific brain areas before neuronal degeneration,providing evidence in experimental models of neurodegenerative disorders,including Parkinson’s and Alzheimer’s diseases.Understanding these mechanisms might increase the insight of these processes and pave the way for new specific glia-targeted therapeutic strategies for neurodegenerative disorders. 展开更多
关键词 ASTROCYTES GLIAL cells microglia NEURODEGENERATIVE diseases NEUROINFLAMMATION Parkinson's disease reactive GLIOSIS selective neuronal degeneration
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Neurotoxic role of interleukin-17 in neural stem cell differentiation after intracerebral hemorrhage 预览
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作者 Lu Gao Ping-Ping Li +6 位作者 Tian-Yu Shao Xiang Mao Hao Qi Bing-Shan Wu Ming Shan Lei Ye Hong-Wei Cheng 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第7期1350-1359,共10页
Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 ... Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 and ICH,we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients.There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients(r=–0.498,P<0.01).To study the neurotoxic role of IL-17,C57 BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus.Subsequently,the mice were treated with mouse neural stem cells(NSCs)and/or IL-17 neutralizing antibody for 72 hours.Flow cytometry,brain water content detection,Nissl staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue,but there was no difference in T cell receptorγδcells.Compared with the ICH group,there were fewer apoptotic bodies and more Nissl bodies in the ICH+NSC group and the ICH+NSC+IL-17 group.To investigate the potential effect of IL-17 on directional differentiation of NSCs,we cultured mouse NSCs(NE-4 C)alone or co-cultured them with T cell receptorγδcells,which were isolated from mouse peripheral blood mononuclear cells,for 7 days.The results of western blot assays revealed that IL-17 secreted by T cell receptorγδcells reduced the differentiation of NSCs into astrocytes and neurons,while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons.In conclusion,serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients.Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of 展开更多
关键词 antibody neutralization ASTROCYTES directional differentiation interleukin 17 intracerebral hemorrhage neural stem cells Nissl staining recovery T cell receptorγδcells TUNEL staining
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Characterization of astrocytes and microglial cells in the hippocampal CA1 region after transient focal cerebral ischemia in rats treated with Ilexonin A 预览
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作者 Ai-Ling Xu Guan-Yi Zheng +2 位作者 Hui-Ying Ye Xiao-Dong Chen Qiong Jiang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第1期78-85,共8页
Ilexonin A is a compound isolated from the root of Ilex pubescens,a traditional Chinese medicine.Ilexonin A has been shown to play a neuroprotective role by regulating the activation of astrocytes and microglia in the... Ilexonin A is a compound isolated from the root of Ilex pubescens,a traditional Chinese medicine.Ilexonin A has been shown to play a neuroprotective role by regulating the activation of astrocytes and microglia in the peri-infarct area after ischemia.However,the effects of ilexonin A on astrocytes and microglia in the infarct-free region of the hippocampal CA1 region remain unclear.Focal cerebral ischemia models were established by 2-hour occlusion of the middle cerebral artery in rats.Ilexonin A(20,40 or 80 mg/kg)was administered immediately after ischemia/reperfusion.The astrocyte marker glial fibrillary acidic protein,microglia marker Iba-1,neural stem cell marker nestin and inflammation markers were detected by immunohistochemistry and western blot assay.Expression levels of tumor necrosis factor-αand interleukin 1βwere determined by enzyme linked immunosorbent assay in the hippocampal CA1 tissue.Astrocytes were activated immediately in progressively increasing numbers from 1,3,to 7 days post-ischemia/reperfusion.The number of activated astrocytes further increased in the hippocampal CA1 region after treatment with ilexonin A.Microglial cells remained quiescent after ischemia/reperfusion,but became activated after treatment with ilexonin A.Ilexonin A enhanced nestin expression and reduced the expression of tumor necrosis factor-αand interleukin 1βin the hippocampus post-ischemia/reperfusion.The results of the present study suggest that ilexonin A has a neuroprotective effect in the hippocampus after ischemia/reperfusion,probably through regulating astrocytes and microglia activation,promoting neuronal stem cell proliferation and reducing the levels of pro-inflammatory factors.This study was approved by the Animal Ethics Committee of the Fujian Medical University Union Hospital,China. 展开更多
关键词 ASTROCYTES HIPPOCAMPAL CA1 REGION ilexonin A MICROGLIA middle CEREBRAL artery OCCLUSION neural stem cell neuroprotection transient focal CEREBRAL ischemia
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Shh通路介导损伤后反应性星形胶质细胞获得干细胞潜能 预览
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作者 许子宁 李晓红 +2 位作者 叶益超 刘晓银 涂悦 《天津医药》 CAS 北大核心 2019年第7期678-682,I0001共6页
目的探讨Shh信号通路对大脑皮质反应性星形胶质细胞(RAS)获得神经干细胞潜能的影响。方法体外原代培养SD大鼠大脑皮质星形胶质细胞,以肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1α和C1q三种因子诱导炎症型RAS,划痕实验制备创伤型RAS,使用... 目的探讨Shh信号通路对大脑皮质反应性星形胶质细胞(RAS)获得神经干细胞潜能的影响。方法体外原代培养SD大鼠大脑皮质星形胶质细胞,以肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1α和C1q三种因子诱导炎症型RAS,划痕实验制备创伤型RAS,使用免疫荧光染色法观察细胞形态及纯度。实验分为普通星形胶质细胞组(对照组)、炎症组、划痕组(创伤组)。炎症组培养至干预后24h,对照组和划痕组培养至第5天进行免疫荧光染色观察巢蛋白(Nestin)阳性细胞,运用Westernblot技术检测不同损伤模型的细胞中Shh蛋白的表达量。之后各组细胞培养至第7天更换神经干细胞培养基,将前述3组各自再分为激活组(各组细胞更换神经干细胞培养基后添加Shh激活剂SAG)和抑制组(各组细胞更换神经干细胞培养基后添加Shh抑制剂环巴胺)两个亚组,培养14d后采用qRT-PCR检测各亚组RAS源性神经干细胞相关基因的表达量。结果细胞损伤模型中,免疫荧光染色证明各组细胞中划痕组Nestin阳性细胞明显多于炎症组和对照组。Westernblot结果显示2组损伤细胞中划痕组Shh蛋白表达量高于炎症组(P<0.05)。更换神经干细胞培养基后,激活组中2组损伤细胞的干细胞相关基因Nestin、Pax-6、Sox-2、Oct-4和Map-2的表达水平均有所升高,其中由划痕诱导的RAS神经干细胞相关基因Nestin、Pax-6、Sox-2、Oct-4和Map-2的表达水平高于炎症诱导的RAS神经干细胞和普通星形胶质细胞(P<0.01);添加Shh抑制剂后,3组上述基因表达量皆明显降低,但划痕组的表达量仍高于其他2组(P<0.01)。结论在体外,Shh信号通路可以介导损伤后大脑皮质RAS获得干细胞潜能。 展开更多
关键词 星形细胞 基因 反应性星形胶质细胞 SHH SAG 环巴胺 神经干细胞
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神经炎症与抑郁症相关的研究进展 预览
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作者 杨可心 《世界最新医学信息文摘(电子版)》 2019年第24期32-33,41共3页
抑郁症是一种常见的、损害严重的、经常复发的精神障碍,近年来人群中出现的不明原因的患病率逐渐上升。关于抑郁症的发病机制存在多种假设,这些假设尚未完全得到证实。最新的研究发现神经炎症与抑郁症的发生有关,NLRP3炎症小体、TNF-α... 抑郁症是一种常见的、损害严重的、经常复发的精神障碍,近年来人群中出现的不明原因的患病率逐渐上升。关于抑郁症的发病机制存在多种假设,这些假设尚未完全得到证实。最新的研究发现神经炎症与抑郁症的发生有关,NLRP3炎症小体、TNF-α细胞因子、星形胶质细胞与小胶质细胞均参与其中,为抑郁症的治疗提供了可能靶点。本文就神经炎症与抑郁症相关的研究进展进行分析。 展开更多
关键词 神经炎症 抑郁症 细胞因子 星形胶质细胞 小胶质细胞
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差速贴壁法在原代星形胶质细胞纯化中的应用 预览
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作者 李艳 张瑜 李斐雪 《杭州师范大学学报:自然科学版》 CAS 2019年第3期268-273,共6页
为获得高纯度的星形胶质细胞,在大鼠新生P0乳鼠大脑皮层的原代培养后,采用差速贴壁法予以纯化.经细胞免疫荧光染色鉴定,差速贴壁30min及1h处理获得的星形胶质细胞纯度高、状态好,能满足神经生物学研究中对高纯度星形胶质细胞培养的实验... 为获得高纯度的星形胶质细胞,在大鼠新生P0乳鼠大脑皮层的原代培养后,采用差速贴壁法予以纯化.经细胞免疫荧光染色鉴定,差速贴壁30min及1h处理获得的星形胶质细胞纯度高、状态好,能满足神经生物学研究中对高纯度星形胶质细胞培养的实验要求,适宜推广. 展开更多
关键词 星形胶质细胞 差速贴壁法 大鼠 原代细胞培养
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The role of connexin43 in neuropathic pain induced by spinal cord injury
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作者 Anhui Wang Changshui Xu 《生物化学与生物物理学报:英文版》 SCIE CAS CSCD 2019年第6期555-561,共7页
Neuropathic pain is caused by the damage or dysfunction of the nervous system. In many neuropathic pain models, there is an increase in the number of gap junction (GJ) channels, especially the upregulation of the expr... Neuropathic pain is caused by the damage or dysfunction of the nervous system. In many neuropathic pain models, there is an increase in the number of gap junction (GJ) channels, especially the upregulation of the expression of connexin43 (Cx43), leading to the secretion of various types of cytokines and involvement in the formation of neuropathic pain. GJs are widely distributed in mammalian organs and tissues, and Cx43 is the most abundant connexin (Cx) in mammals. Astrocytes are the most abundant glial cell type in the central nervous system (CNS),which mainly express Cx43. More importantly, GJs play an important role in regulating cell metabolism, signaling, and function. Many existing literatures showed that Cx43 plays an important role in the nervous system, especially in the CNS under normal and pathological conditions. However, many internal mechanisms have not yet been thoroughly explored. In this review, we summarized the current understanding of the role and association of Cx and pannexin chan nets in neuropathic pain, especially after spinal cord injury, as well as some of our own in sights and thoughts which suggest that Cx43 may become an emerging therapeutic target for future neuropathic pain, bringing new hope to patients. 展开更多
关键词 connexin43 astrocytes gap junction NEUROPATHIC pain SPINAL CORD injury
FGF21对Aβ25-35导致星形胶质细胞损伤的保护作用及机制研究 预览
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作者 孙岩 高向东 陈松 《中国药科大学学报》 CAS CSCD 北大核心 2019年第4期490-496,共7页
以Aβ25-35诱导星形胶质细胞建立损伤模型,探讨阿尔茨海默病(Alzheimer′s disease,AD)样病变中成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)对星形胶质细胞的作用及机制。采用Aβ25-35诱导C6星形胶质细胞株及原代星形胶... 以Aβ25-35诱导星形胶质细胞建立损伤模型,探讨阿尔茨海默病(Alzheimer′s disease,AD)样病变中成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)对星形胶质细胞的作用及机制。采用Aβ25-35诱导C6星形胶质细胞株及原代星形胶质细胞损伤建立细胞模型;以不同浓度的FGF21对Aβ25-35诱导细胞损伤模型干预,MTT法检测细胞活性;采用DCFH-DA探针结合流式细胞仪检测FGF21及Aβ25-35对C6细胞内活性氧(reactive oxygen species,ROS)水平的作用;Western blot检测FGF21及Aβ25-35对C6细胞中丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPKs)活性的影响。结果显示:FGF21能够减少Aβ25-35导致C6细胞及原代星形胶质细胞的损伤,下调C6细胞内异常ROS水平,同时缓解Aβ25-35引起的C6细胞MEK1/2、ERK1/2、p38磷酸化水平的异常,提示FGF21可能通过调控ROS途径及MAPKs信号通路进而缓解Aβ25-35导致的星形胶质细胞损伤。 展开更多
关键词 成纤维细胞生长因子21 阿尔茨海默病 星形胶质细胞 活性氧 丝裂原活化蛋白激酶
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内源性干细胞对小鼠出血性脑损伤的修复作用 预览
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作者 黄子珂 宋越强 +2 位作者 张熙 童伟芳 李思光 《同济大学学报:医学版》 CAS 2019年第4期406-412,共7页
目的探究内源性CD133^+干细胞及脑损伤后获得干性的细胞对出血性脑损伤的修复作用。方法建立CD133^+细胞谱系示踪小鼠(CD133-Cre-ERT2;CAG-loxP-STOP-loxP-ZsGreen)。将24只CD133^+细胞示踪小鼠随机分为出血组与假手术组,每组12只,其中... 目的探究内源性CD133^+干细胞及脑损伤后获得干性的细胞对出血性脑损伤的修复作用。方法建立CD133^+细胞谱系示踪小鼠(CD133-Cre-ERT2;CAG-loxP-STOP-loxP-ZsGreen)。将24只CD133^+细胞示踪小鼠随机分为出血组与假手术组,每组12只,其中出血组再随机分为损伤后1、3、7、14 d组,每组3只。将30 μL自体尾静脉血立体定位注射至小鼠纹状体,在损伤后1、3、7、14 d分别进行神经功能损伤评分。采用免疫荧光法观察并统计损伤后1、3、7、14 d损伤侧及对侧相应位置PDGFRβ^+、GFAP^+细胞数量,以及损伤侧与对侧SVZ区DCX^+与DCX^+/ZsGreen^+细胞数量;采用PDGFRβ和Nestin抗体、Ki67和GFAP抗体组合免疫荧光法观察损伤侧纹状体周细胞干性获得以及新生星形胶质细胞的情况。结果损伤后1、3、7、14 d时损伤侧纹状体星形胶质细胞数量明显多于对照侧相应位置,差异具有统计学意义(P<0.05),且损伤侧纹状体星形胶质细胞数量随时间增加而进一步增加;而损伤后两侧周细胞的数量差异无统计学意义,且数量不随时间的增加而变化;损伤后7 d出血侧SVZ区有10.35%±3.01%DCX^+细胞与ZsGreen信号共定位,出血侧SVZ区的DCX^+细胞及DCX^+/Zsgreen^+细胞在损伤后7 d时数量最多且明显多于对照侧(P<0.05),而损伤后1、3、14 d时DCX^+与DCX^+/ZsGreen^+两种细胞数量较低。损伤灶周有少量GFAP^+/Ki67^+细胞与ZsGreen信号共定位,同时灶周一些PDGFRβ^+细胞与Nestin信号共定位。结论内源性CD133^+细胞在脑出血损伤后能向成神经细胞、星形胶质细胞方向分化,参与神经修复;且出血侧纹状体星形胶质细胞大量增殖,部分血管周细胞获得干性,对神经系统修复产生潜在作用。 展开更多
关键词 脑出血 内源性干细胞 CD133 周细胞 星形胶质细胞 小鼠
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电离辐射激活海马星形胶质细胞诱导小鼠认知功能障碍 预览 被引量:1
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作者 王贞 罗诗诗 +8 位作者 牛磊 乃爱桃 徐杨 刘政海 何洁 何淑雅 钟小林 万炜 曹文宇 《辐射研究与辐射工艺学报》 CAS CSCD 2019年第1期20-26,共7页
探讨电离辐射引起小鼠认知功能障碍的可能机制。24只雌性昆明小鼠随机分为对照组和辐照组,辐照组小鼠接受137Csγ射线单次全身辐照至吸收剂量4 Gy。35 d后采用Y迷宫实验检测小鼠认知功能;免疫组织化学法检测小鼠海马区星形胶质细胞(Astr... 探讨电离辐射引起小鼠认知功能障碍的可能机制。24只雌性昆明小鼠随机分为对照组和辐照组,辐照组小鼠接受137Csγ射线单次全身辐照至吸收剂量4 Gy。35 d后采用Y迷宫实验检测小鼠认知功能;免疫组织化学法检测小鼠海马区星形胶质细胞(Astrocytes,Ast)标记物胶质纤维酸性蛋白(Glial fibrillary acidic protein,GFAP)阳性细胞数的表达变化;Western blot方法检测海马GFAP蛋白的表达变化;荧光定量PCR检测炎性因子白细胞介素IL-1α、IL-1β、IL-6 mRNA和海马GFAP的表达情况。结果表明:与对照组相比,辐照组小鼠在Y迷宫实验中自发交替率明显降低(78.40±4.16 vs. 67.53±3.08,p<0.05);海马区GFAP阳性细胞数明显增加(133.4±9.6 vs. 280.3±32.7,p<0.01);GFAP蛋白及mRNA表达均显著上调(1.000±0.036vs. 1.300±0.102,p<0.05;1.000±0.031 vs. 1.203±0.078,p<0.05);IL-1α、IL-1β和IL-6 mRNA的表达均明显上调(1.000±0.133 vs. 1.677±0.164,p<0.01;1.000±0.132 vs. 1.488±0.105,p<0.05;1.000±0.218 vs.2.181±0.188,p<0.01)。研究提示,电离辐射可能是通过激活海马Ast诱导炎症因子释放,从而引起认知功能障碍。 展开更多
关键词 电离辐射 海马 星形胶质细胞 认知功能障碍
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Effect of acupuncture on the ultrastructure of neurons and astrocytes in the hippocampal dentate gyrus in rats with Alzheimer’s disease induced by Aβ1-42
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作者 汤双红 《中国医学文摘:内科学分册(英文版)》 2019年第2期65-66,共2页
Objective To observe the effects of acupuncture at'Baihui'(GV 20) and'Shenshu'(BL 23) on the ultrastructure of hippocampal dentate gyrus in rats with Alzheimer’s disease. Methods Forty SPF Wistar male... Objective To observe the effects of acupuncture at'Baihui'(GV 20) and'Shenshu'(BL 23) on the ultrastructure of hippocampal dentate gyrus in rats with Alzheimer’s disease. Methods Forty SPF Wistar male rats were randomly divided into normal group,sham operation group,model group and acupuncture group,10 rats in each one. 展开更多
关键词 the ULTRASTRUCTURE of NEURONS and ASTROCYTES Alzheimer’s disease INDUCED by A Alzheimer
自身免疫性胶质纤维酸性蛋白星形细胞病患者脊髓磁共振成像及临床特征分析
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作者 徐辉明 黄清梅 +8 位作者 肖小玉 刘天妮 陈百铿 杨华才 刘思 杨洁 黄莉 龙友明 高聪 《中华神经科杂志》 CAS CSCD 北大核心 2019年第2期92-97,共6页
目的 分析国人自身免疫性胶质纤维酸性蛋白(GFAP)星形细胞病患者的脊髓病变的磁共振成像(MRI)特征及其相关临床特点。 方法 使用基于组织法及细胞法检测2013年3月至2018年6月在广州医科大学附属第二医院神经内科收集的1 040份脑脊液和... 目的 分析国人自身免疫性胶质纤维酸性蛋白(GFAP)星形细胞病患者的脊髓病变的磁共振成像(MRI)特征及其相关临床特点。 方法 使用基于组织法及细胞法检测2013年3月至2018年6月在广州医科大学附属第二医院神经内科收集的1 040份脑脊液和血清标本,发现42例GFAP抗体阳性患者,回顾性分析脑脊液GFAP抗体阳性同时存在脊髓病灶的19例自身免疫性GFAP星形细胞病患者的脊髓MRI资料及其临床资料。 结果 19例患者中,女性12例,男性7例;发病年龄(44±17)岁。患者的主要临床表现为肢体麻木无力(14/19)、视力障碍(5/19)、头痛(4/19)、癫痫发作(4/19)、认知障碍(3/19)等。脊髓MRI提示,脊髓病灶仅累及颈段脊髓者5例(5/19),仅累及胸段脊髓者8例(8/19),同时累及颈胸段脊髓者6例(6/19);脊髓受累长度超过3个脊髓节段者15例(15/19);脊髓病灶有强化者7例(7/19);脊髓病灶合并有颅内病灶者8例(8/19);病灶累及脊髓灰质19例(19/19)。 结论 自身免疫性GFAP星形细胞病患者女性多于男性,患者的脑部和脊髓可以同时受累,患者的脊髓MRI表现形式复杂,脊髓受累节段一般较长,并且以累及脊髓灰质为主,脊髓病灶多累及胸段脊髓,仅累及颈段脊髓较少,腰段脊髓基本不受累。 展开更多
关键词 自身免疫疾病 胶质纤维酸性蛋白 星形细胞 脊髓 磁共振成像
Dynamic Change of Matrix Stiffness Switches Astrocyte Phenotype in Three Dimensions
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作者 Yan Hu Jin Tian +3 位作者 Jinbin Qiu Dayun Feng Guoyou Huang Feng Xu 《医用生物力学》 CAS CSCD 北大核心 2019年第A01期135-136,共2页
Background Damage to the central nervous system(CNS)usually leads to the activation of astrocytes,followed by glial scar formation.For years,glial scar has been thought as a major obstacle for successful axon regenera... Background Damage to the central nervous system(CNS)usually leads to the activation of astrocytes,followed by glial scar formation.For years,glial scar has been thought as a major obstacle for successful axon regeneration.However,increasing evidence suggests a beneficial role for this scar tissue as part of the endogenous local immune regulation and repair process.Surprisingly,in contrast to scars in other tissues,glial scars(mainly consist of reactive astrocytes)in both rat cortex and spinal cord were recently found to be significantly softer than healthy CNS tissues.Naive astrocytes have been found to change their phenotype to reactive astrocytes and gradually into scar-forming astrocytes,upregulating the astrocyte marker glial fibrillary acidic protein(GFAP),vimentin,and inflammatory proteins in almost all known brain disorders.Such phenotype transformation process has been widely thought unidirectional or irreversible.However,recent research revealed the environment-dependent plasticity of astrocyte phenotypes,with reactive astrocytes could revert in retrograde to naive astrocytes in proper microenvironment.In consideration of the important roles of mechanical cues in CNS and the unique softening behavior of glial scars,it is of great interesting to study the effects of dynamic changes of matrix stiffness on astrocyte phenotypic switch.Materials&methods Primary astrocyes were isolated from the cortex of SpragueDawley(SD)rats at PI.After cultured for 2 weeks,astrocytes were encapsulated into a set of three-dimensional(3D)hybrid hydrogel system composed of type I collagen and alginate.Immunofluorescence and Western blot expression analysis were applied for characterizting cell responses to different and dynamically changed matrix stiffness.A molecular dynamics model was developed for simulation.Results&discussion In this work,we established an in-vitro model to study the effects of dynamic changes of matrix stiffness on astrocyte phenotypic switchings in 3D.To simulate native cellular environment,we fabricated 展开更多
关键词 ASTROCYTES MATRIX STIFFNESS HYDROGELS three dimensions YAP
柴胡皂苷a抑制PTZ诱导的小鼠海马星形胶质细胞活化 预览
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作者 单萍 张继龙 +1 位作者 笱玉兰 罗利俊 《中国病理生理杂志》 CAS CSCD 北大核心 2019年第3期485-490,共6页
目的:探讨柴胡皂苷a(SSa)对戊四氮(PTZ)诱导的小鼠海马星形胶质细胞活化的抑制作用。方法:分离培养小鼠海马星形胶质细胞,将细胞随机分为对照组、PTZ组、PTZ+0.625 mg/L SSa组和PTZ+1.25 mg/L SSa组。通过免疫荧光染色检测胶质细胞原纤... 目的:探讨柴胡皂苷a(SSa)对戊四氮(PTZ)诱导的小鼠海马星形胶质细胞活化的抑制作用。方法:分离培养小鼠海马星形胶质细胞,将细胞随机分为对照组、PTZ组、PTZ+0.625 mg/L SSa组和PTZ+1.25 mg/L SSa组。通过免疫荧光染色检测胶质细胞原纤维酸性蛋白(GFAP)的表达来鉴定细胞;用MTT检测评估细胞活力;用流式细胞术检测各组细胞的周期变化;ELISA法检测各组细胞中GFAP和间隙连接蛋白43(Cx43)的表达水平;流式细胞术和Hoechst 33258染色检测各组细胞的凋亡情况。结果:体外原代培养的星形胶质细胞贴壁生长,细胞突起明显。免疫荧光显示星形胶质细胞呈GFAP阳性表达。与对照组比较,PTZ组细胞活力和G2/M期细胞百分比显著增加(P<0.05),GFAP和Cx43的表达水平也显著上调(P<0.05);与PTZ组比较,PTZ+0.625 mg/L SSa组和PTZ+1.25 mg/L SSa组细胞活力和G2/M期细胞百分比均明显下降,GFAP和Cx43的表达水平也降低,但细胞凋亡水平显著增加(P<0.05)。结论:SSa能够显著抑制PTZ诱导的海马星形胶质细胞活化,抑制细胞增殖并诱导凋亡。 展开更多
关键词 癫痫 星形胶质细胞 柴胡皂苷A 戊四氮 细胞凋亡
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丹参酮ⅡA对大鼠脊髓损伤后星形胶质细胞增殖的MAPK通路的影响
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作者 于宝龙 李瑞峰 李文选 《中国生物制品学杂志》 CAS CSCD 2019年第5期535-537,共3页
目的探讨丹参酮ⅡA(tanshinoneⅡA,TⅡA)对大鼠脊髓损伤(spinal cord injury,SCI)后星形胶质细胞增殖的MAPK通路的影响。方法建立大鼠SCI模型,获得星形胶质细胞,培养14 d后,采用免疫荧光法检测星形胶质细胞中胶质纤维酸性蛋白(glial fib... 目的探讨丹参酮ⅡA(tanshinoneⅡA,TⅡA)对大鼠脊髓损伤(spinal cord injury,SCI)后星形胶质细胞增殖的MAPK通路的影响。方法建立大鼠SCI模型,获得星形胶质细胞,培养14 d后,采用免疫荧光法检测星形胶质细胞中胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)的表达;MTT法选择TⅡA抑制星形胶质细胞生长的最适浓度和时间;Western blot法检测MAPK通路各蛋白的磷酸化情况。结果星形胶质细胞中有GFAP特异性表达;TⅡA抑制星形胶质细胞生长的最适浓度为15μg/mL,最适作用时间为36 h;15μg/mL TⅡA作用0和4 h,星形胶质细胞中p-JNK高于8和12 h,ERK1/2和p38无变化。结论 TⅡA主要通过JNK依赖性途径对星形胶质细胞的生长进行调控。 展开更多
关键词 丹参酮ⅡA 脊髓损伤 星形胶质细胞 MAPK通路
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