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Influence of endogenous ciliary neurotrophic factor on neural differentiation of adult rat hippocampal progenitors

Neural Regeneration Research 2013年第4期8卷 301-312页

作者： Jun Ding Zhili He Juan Ruan Ying Liu Chengxin Gong shenggang sun Honghui Chen Department of Neurology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Mental Health Center Tongji Medical CollegeHuazhong University of Science and Technology New York State Institute for Basic Research in Developmental Disabilities Staten IslandNYUSA

Ciliary neurotrophic factor is the only known neurotrophic factor that can promote differentiation of hippocampal neural progenitor cells to glial cells and neurons in adult rats. This process is similar to spontaneous differentiation. Therefore, ciliary neurotrophic factor may be involved in spontaneous differentiation of neural stem cells. To verify this hypothesis, the present study isolated neural progenitor cells from adult male rats and cultured them in vitro. Results showed that when neural progenitor cells were cultured in the absence of mitogen fibroblast growth factor-2 or epidermal growth factor, they underwent spontaneous differentiation into neurons and glial cells. Western blot and immunocytochemical staining showed that exogenous ciliary neurotrophic factor strongly induced adult hippocampal progenitor cells to differentiate into neurons and glial cells. Moreover, passage 4 adult hippocampal progenitor cells expressed high levels of endogenous ciliary neurotrophic factor, and a neutralizing antibody against ciliary neurotrophic factor prevented the spontaneous neuronal and glial differentiation of adult hippocampal progenitor cells. These results suggest that the spontaneous differentiation of adult hippocampal progenitor cells is mediated partially by endogenous ciliary neurotrophic factor.

关键词： neural regeneration stem cells spontaneous differentiation neural progenitor cells endogenous neurotrophic factors ciliary neurotrophic factor regeneration grants-supported paper photographs-containing paper neuroregeneration

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Effects of endoplasmic reticulum stress and related apoptosis on selective death of dopaminergic neurons

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Journal of Nanjing Medical University 2006年第4期20卷 229-233页

作者： Lan Wang~, shenggang sun~, Xuebing Cao~, Zhentao Zhang~ and Li Xu~ shenggang sun Xuebing Cao Zhentao Zhang Li Xu Department of Neurology Union Hospital Tongji Medical Collge Huazhong University of Science and Technlogy WuHan 430022China

Objective： To explore the mechanism of endoplasmic reticulum stress（ERS） response and related apoptosis in dopaminergic neurons death. Methods： Nerve growth factor （NGF）-treatedPC12 cells were treated with 6-OHDA, MPP^＋ and rotenone. MTT assay and flow cytometry were used to measure the cell viability and the rate of celluar apoptosis induced by those neurotoxins. The expression of ERS-related gene XBP1, Grp78, CHOP, caspase-12 in drug-treated group and reserpine preincubafion group was determined with RT-polymerase chain reaction（RT-PCR） and immunohistochemistry. Results： After the exposure to different toxins, the viability of PC12 cells were decreased by 52%, 44%, 40% at 100μM6-OHDA, 75 μM MPP^＋, 20 nM rotenone for 24 h respectively. FCM assay confirmed time-dependent cell apoptosis （P 〈 0.01 ）. The gene and protein expression of XBP1, Grp78 in drug-treated group were significantly increased and reached their peaks 8 h after the treatment（P 〈 0.05）. The expression levels of CHOP and caspase-12 gene were increased 16-24 h after the treatment（P 〈 0.01 ）, but the expression level of caspase-12 was inhibited by reserpine preincubayion（P 〈 0.05）. Conclusion： The excessive ERS and relative activated cell apoptosis pathway may be associated with selective death of dopaminergic neurons.

关键词： endoplasmic reticulum stress apoptosis dopamine Parkinson's disease

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Functional localization of epileptic foci in cats using manganese-enhanced MRI

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Journal of Nanjing Medical University 2006年第4期20卷 214-219页

作者： Qingxia Kong shenggang sun Changqin Liu Jinbai Hung Haibo Xu Department of Neurology Department of imageology Union Hospital Tongji Medical College Huazhong University of Science and TechnologyWuhan 430022China

Objective： To determine the encephalic region correlated with epilepsy by manganese-enhanced MRI （MEMRI） and determine the correlation of epilepsy with calcium overloading. Methods： The cats were divided into two groups. The first group underwent EEG examination and ethological observation. The second group underwent MEMRI measurement. Signal enhanced encephalic regions were sectioned. Results： The achievement ratio of convulsive cats intramusclelarly injected with PTZ was 80%. MEMRI showed diffuse signal enhancement in the cerebral cortex of the cats with generalized tonic-clonic convulsive seizures compared with control animals. The enhancement rate of frontal-parietal-occipital lobe was 34.6% and 22.9% in temporl lobe compared with the control groups. Signal enhancement on frontal-parietal lobe persisted for 24 h after epileptic seizures were induced. The neurons of enhanced encephalic regions showed obvious degeneration and necrosis. Conclusion： Seizures can be induced in cats by intramuscular injection of PTZ （55 mg/kg）. Frontal-parietal lobe is the correlated encephalic regions of epilepsy. MEMRI plays an important role in localizing and revealing pathogenesis of epileptic seizures.

关键词： Mn^2+ manganese-enhanced MRI epilepsy blood-brain barrier

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The role of nerve growth factor inducible protein B in the pathogenesis of levodopa-induced dyskinesias

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Journal of Nanjing Medical University 2006年第2期20卷 79-82页

作者： Xuebing Cao Yixuan Niu Yan Xu Guanglei Yuan Guirong Wei shenggang sun Department of Neurology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022China

Objective： To study the role of the expression of nerve growth factor inducible protein B gene （NGFI-B） in striatum in the pathogenesis of levodopa-induced dyskinesias （LID）. Methods： The rat model of LID was treated with SCH 23390（1 mg/kg ip,a dopamine D1 antagonist） and haloperidol （1 mg/kg ip,a dopanfme D2 antagonist） respectively. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to measure the expression of NGFI-B mRNA in stiiatam and the behavior changes were observed. Resuits： After treatment with SCH23390, abnormal involuntary movement （AIM） in LID rats was decreased （ P 〈 0.05 ） and the expression of NGFI-B mRNA in striatum did not change significantly. After treatment with haloperidol, the changes of AIM in LID rats were not significant and the expression of NGFI-B mRNA was increased significantly（ P 〈 0.01）. Conclusion： LID is associated with over-expression of NGFI-B in striatum. Abnormal activity in the direct pathway and the basal ganglia circuit could be involved in the occurrence of LID.

关键词： levodopa-induced dyskinesias levodopa Parkinson' s disease nerve growth factor inducible proteinB

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Experimental Study on Inhibition of Neuronal Toxical Effect of Levodopa by Ginkgo Biloba Extract on Parkinson Disease in Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2003年第2期23卷 151-153页

作者：曹非孙圣刚童萼塘 Department of Neurology Xiehe HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan 430022

In order to observe neuronal toxical effect of Levodopa and investigate if using Levodopa together with Ginkgo Bilobar Extract (EGb) would be an workable method to treat Parkinson disease, rat models of Parkinson disease (PD) were made by injecting 6-OHDA stereotaxically to right side of the mesencephic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Rotational behavioral observation, TUNEL, immunocytochemistry, Nissl's body staining were performed to measure the difference between group treated by Levodopa (50 mg/kg every day for 3 days, 5 days, 7 days, L-dopa group) and group treated by Levodopa combined with EGb (100 mg/ kg every day, E-D group). The results showed that in the L-dopa group, the numbers of apoptosis of substantial nigra, rings of rotational behavior were more than those in the E-D group (P<0. 05). The numbers of Nissl's cells in L-dopa group were fewer than in E-D group (P<0. 05). The results suggested that Levodopa had neur toxic effect and EGb may decrease the toxicity of levodopa. The combined use of EGb with Levodopa may be a workable method to treat PD and may be better than using Levodopa alone.

关键词： ginkgo biloba extract apoptosis L-dihydroxy-phenylalanine

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亚低温对脑缺血再灌注后血脑屏障损伤及明胶酶活性的影响

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中国康复医学杂志 2007年第10期22卷 893-896页

作者：苏颖孙圣刚华中科技大学同济医学院附属协和医院神经内科湖北武汉430022

目的:应用MRI动态监测亚低温对脑缺血再灌注后血脑屏障损伤的影响,并探讨其保护机制。方法:雄性Wistar大鼠42只,随机分为常温缺血组、亚低温缺血组和假手术组。线栓法建立大鼠大脑中动脉缺血再灌注模型,分别于再灌注3.5h、24h和5d行T1W... 详细信息

目的:应用MRI动态监测亚低温对脑缺血再灌注后血脑屏障损伤的影响,并探讨其保护机制。方法:雄性Wistar大鼠42只,随机分为常温缺血组、亚低温缺血组和假手术组。线栓法建立大鼠大脑中动脉缺血再灌注模型,分别于再灌注3.5h、24h和5d行T1WI增强扫描,再灌注24h和5d进行大鼠神经功能缺损评分,脑组织明胶酶活性测定,以及明胶酶活性与磁共振表现的相关分析。结果:亚低温治疗明显减小了各时间点T1WI信号强化的范围和强度,显著降低缺血再灌注早期及晚期神经功能缺损评分和脑组织明胶酶活性。常温缺血组再灌注24h后MMP-9活性与T1WI信号强化范围正相关。结论:亚低温能明显减轻缺血再灌注后血脑屏障损伤的范围和程度,促进神经功能恢复,其保护机制可能与亚低温降低MMP-9、MMP-2的活性有关。

关键词：脑缺血亚低温血脑屏障明胶酶磁共振成像

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Cytokine-Induced Cell Surface Expression of Adhesion Molecules in Vascular Endothelial Cells In vitro

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2001年第1期21卷 68-71页

作者：陈红辉刘昌勤孙圣刚梅元武童萼塘 Department of Neurology Xiehe Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022

Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF α (1-250 U/ml) or IL 1β (0.1-50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF α (100 U/ml) or IL 1β (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules (ICAM 1 and VCAM 1) were detected and quantitated by immunocytochemical methods and computerized imaging analysis technique. Adhesion molecules expression were up regulated by TNF α, IL 1β in a concentration and time dependent manner. Some significant differences were observed between the effects of cytokines on the ICAM 1 and on VCAM 1 expression. Cytokines might directly induce the expression of ICAM 1 and VCAM 1 in vascular endothelial cells. Our observations indicate differential functions of the two adhesion molecules during the evolution of inflammatory responses in stroke.

关键词： tumor necrosis factor α interleukin 1β adhesion molecule intercellular adhesion molecule 1 vascular cell adhesion molecule 1

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一种基于PIO改进强化学习的航天器复杂多约束姿态机动规划新方法

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中国科学：技术科学 2023年第2期53卷 200-209页

作者：华冰孙胜刚吴云华陈志明南京航空航天大学航天学院南京210016

本文针对多个姿态约束条件下的航天器姿态机动规划问题进行了研究,提出了一种基于鸽群算法的改进的策略梯度强化学习算法(PIOPGRL).首先,针对强制指向约束和禁止指向约束,建立了基于角度的姿态约束模型,根据约束模型建立了强化学习的回... 详细信息

本文针对多个姿态约束条件下的航天器姿态机动规划问题进行了研究,提出了一种基于鸽群算法的改进的策略梯度强化学习算法(PIOPGRL).首先,针对强制指向约束和禁止指向约束,建立了基于角度的姿态约束模型,根据约束模型建立了强化学习的回报函数.然后,使用适应度函数替代策略评价函数,将鸽群算法与强化学习相融合.针对策略梯度强化学习算法计算量大、收敛速度慢的问题,使用鸽群算法求解策略梯度,极大减少了计算量.仿真结果表明,相比于策略梯度强化学习算法,基于自PIO改进强化学习的航天器姿态机动规划算法(PIOPGRL)在极大减少计算量的同时,有更优的规划结果,更小的机动代价,适用于微小航天器解决多个姿态约束条件下的姿态机动规划问题.

关键词：姿态机动姿态约束路径规划强化学习鸽群算法航天器

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姜黄素通过抗氧化作用拮抗鱼藤酮致PC12细胞损伤的研究

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华中科技大学学报（医学版） 2010年第1期39卷 37-41,46页

作者：崔群力孙圣刚华中科技大学同济医学院附属协和医院神经科武汉430022

目的探讨姜黄素(Cur)对鱼藤酮(Ro)致PC12细胞损伤的保护作用及其机制。方法用鱼藤酮建立PC12细胞损伤模型;用四氮唑盐(MTT)比色法检测细胞增殖活力;苏木精-伊红染色观察细胞形态学变化;比色法检测细胞内总超氧化物歧化酶(SOD)的活性;DCF... 详细信息

目的探讨姜黄素(Cur)对鱼藤酮(Ro)致PC12细胞损伤的保护作用及其机制。方法用鱼藤酮建立PC12细胞损伤模型;用四氮唑盐(MTT)比色法检测细胞增殖活力;苏木精-伊红染色观察细胞形态学变化;比色法检测细胞内总超氧化物歧化酶(SOD)的活性;DCFH-DA染色检测细胞内活性氧类物质(ROS)水平;流式细胞术(AnnexinⅤ-FITC/PI双染法)检测PC12细胞的凋亡。结果0.5μmol/L姜黄素和1.0μmol/L姜黄素均可减轻0.1μmol/L鱼藤酮对PC12细胞增殖活力的抑制,与鱼藤酮组比较差异有统计学意义(P<0.01);明显减轻了细胞损伤的形态学改变;明显增加了PC12细胞内SOD的活性,与鱼藤酮组比较差异有统计学意义(P<0.05);明显降低了PC12细胞内ROS的含量,明显抑制了鱼藤酮对PC12细胞凋亡的诱导作用,与鱼藤酮组比较差异均有统计学意义(均P<0.01)。结论姜黄素可拮抗鱼藤酮致PC12细胞的损伤,其机制可能与清除细胞内ROS,诱导抗氧化酶的活性有关。

关键词：姜黄素鱼藤酮 PC12细胞超氧化物歧化酶活性氧类物质

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大鼠脑外伤灶周突触和星形胶质细胞的变化及对GM1的反应

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中国综合临床 2006年第10期22卷 875-877页

作者：谭来勋孙圣刚武汉大学人民医院神经科武汉430060 华中科技大学同济医学院附属协和医院神经科

目的研究实验性大鼠脑外伤病灶周围(A区)突触与星形胶质细胞的数目和功能的变化及单唾液酸四己糖神经节苷脂(GM1)对其的作用。方法经落体撞击法将120只大鼠造成左顶脑挫裂伤,随机分为外伤、抑制、GM1和盐水组;每组在病程7、14和28 d分... 详细信息

目的研究实验性大鼠脑外伤病灶周围(A区)突触与星形胶质细胞的数目和功能的变化及单唾液酸四己糖神经节苷脂(GM1)对其的作用。方法经落体撞击法将120只大鼠造成左顶脑挫裂伤,随机分为外伤、抑制、GM1和盐水组;每组在病程7、14和28 d分别用电镜和免疫组织化学法观察A区星形胶质细胞(AC)和突触数目、胶质纤维酸性蛋白(GFAP)、突触素(SYP)和生长相关蛋白43(GAP-43)免疫反应强度。结果第7、14、28天外伤组大鼠A区突触和AC数目,GFAP和SYP免疫反应强度均高于抑制组,均随病程而显著增加;GM1和盐水组各数据又均高于外伤组(P<0.01)。结论大鼠脑外伤A区突触数目增多、功能增强与AC增殖及功能活动有密切关系,GM1对此有益。

关键词：脑外伤突触星形胶质细胞单唾液酸四己糖神经节苷脂大鼠

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