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outgrowth endothelial cells form a functional cerebral barrier and restore its integrity after damage

Neural Regeneration Research 2020年第6期15卷 1071-1078页

作者： Rais Reskiawan Abdulkadir Mansour Alwjwaj Othman Ahmad Othman Kamini Rakkar Ulvi Bayraktutan Stroke Division of Clinical Neuroscience Clinical Sciences Building School of MedicineHucknall Road Nottingham NG5 1PB UK

Breakdown of blood-brain barrier,formed mainly by brain microvascular endothelial cells(BMECs),represents the major cause of mortality during early phases of ischemic ***,discovery of novel agents that can effectively replace dead or dying endothelial cells to restore blood-brain barrier integrity is of paramount importance in stroke *** endothelial progenitor cells(EPCs)represent one such agents,their rarity in peripheral blood severely limits their adequate isolation and therapeutic use for acute ischemic stroke which necessitate their ex vivo expansion and generate early EPCs and outgrowth endothelial cells(OECs)as a *** analyses of these cells,in the present study,demonstrated that only OECs endocytosed DiI-labelled acetylated low-density lipoprotein and formed tubules on matrigel,prominent endothelial cell and angiogenesis markers,*** analyses by flow cytometry demonstrated that OECs expressed specific markers for sternness(CD34),immaturity(CD133)and endothelial cells(CD31)but not for hematopoietic cells(CD45).Like BMECs,OECs established an equally tight in vitro model of human BBB with astrocytes and pericytes,suggesting their capacity to form tight *** injury mimicked by concurrent deprivation of oxygen and glucose(4 hours)or deprivation of oxygen and glucose followed by reperfusion(20 hours)affected both barrier integrity and function in a similar fashion as evidenced by decreases in transendothelial electrical resistance and increases in paracellular flux,*** scratch assays comparing the vasculoreparative capacity of cells revealed that,compared to BMECs,OECs possessed a greater proliferative and directional migratory *** a triple culture model of BBB established with astrocytes,pericytes and BMEC,exogenous addition of OECs effectively repaired the damage induced on endothelial layer in serum-free *** together,these data demonstrate that OECs may effect

关键词： cell-based therapy endothelial progenitor cells endothelium ischemic stroke neurodegeneration novel therapeutics outgrowth endothelial cells regenerative medicine stem cells translational medicine

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Distinct functions of Trio GEF domains in axon outgrowth of cerebellar granule neurons

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Journal of Genetics and Genomics 2019年第2期46卷 87-96页

作者： Tao Tao Jie Sun Yajing Peng Pei Wang Xin Chen Wei Zhao Yeqiong Li Lisha Wei Wei Wang Yanyan Zheng Ye Wang Xuena Zhang Min-Sheng Zhu Model Animal Research Center State Key Laboratory of Pharmaceutical Biotechnology Department of Neurology of the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School Nanjing University

As a critical guanine nucleotide exchange factor(GEF) regulating neurite outgrowth, Trio coordinates multiple processes of cytoskeletal dynamics through activating Rac1, Cdc42 and RhoA small GTPases by two GEF domains, but the in vivo roles of these GEF domains and corresponding downstream effectors have not been determined yet. We established multiple lines of knockout mice and assessed the respective roles of Trio GEF domains and Rac1 in axon outgrowth. Knockout of total Trio in cerebellar granule neurons(CGNs) led to an impaired F-actin rearrangement of growth cone and hence a retarded neurite outgrowth. Such a retardation was reproduced by inhibition of GEF1 domain or knockdown of Cdc42 and restored apparently by introduction of active Cdc42. As Rac1 deficiency did not affect the neurite outgrowth of CGNs, we suggested that Trio GEF1-mediated Cdc42 activation was required for neurite outgrowth. We established a GEF2-knockout line with deletion of all Trio isoforms except a cerebella-specific Trio8, a short isoform of Trio without GEF2 domain, and used this line as a GEF2-deficient animal model. The GEF2-deficient CGNs had a normal neurite outgrowth but abolished Netrin-1-promoted growth, without affecting Netrin-1 induced Rac1 activation. We thus suggested that Trio GEF1-mediated Cdc42 activation rather than Rac1 activation drives the F-actin dynamics necessary for neurite outgrowth, while GEF2 functions in Netrin-1-promoted neurite elongation. Our results delineated the distinct roles of Trio GEF domains in neurite outgrowth, which is instructive to understand the pathogenesis of clinical Trio-related neurodevelopmental disorders.

关键词： Trio GEF Rho GTPases Axon outgrowth Cerebellar granule neuron

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Safflower Yellow Compounds Alleviate Okadaic Acid-Induced Impairment of Neurite outgrowth in Differentiated SH-SY5Y Cells

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Biomedical and Environmental Sciences 2020年第10期33卷 812-816页

作者： WANG Zhen Hua SHI Xiao Bing LI Gang HAO Xue Yan YUAN Zhen Zhen CAO Xiao Hai WANG Hong Lun LI Ji MA Cheng Jun Center for Mitochondria and Healthy Aging College of Life SciencesYantai UniversityYantai 264005ShandongChina State Key Laboratory of Plateau Ecology and Agriculture Qinghai UniversityXining 810016QinghaiChina Key Laboratory of Tibetan Medicine Research Northwest Institute of Plateau BiologyChinese Academy of SciencesXining 810008QinghaiChina

The dynamic assembly of microtubules plays a key role in maintaining structural and functional integrity of eukaryotic cel s,especial y with regard to neuronal differentiation or neurite outgrowth and synaptic plastic... 详细信息

关键词： outgrowth formation. integrity

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Effects of salvianolic acid B on proliferation, neurite outgrowth and differentiation of neural stem cells derived from the cerebral cortex of embryonic mice

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Science China(Life Sciences) 2010年第6期53卷 653-662页

作者： GUO GuoQing1,LI Bin1,WANG YuanYuan1,SHAN AiJing1,SHEN WeiZai1,YUAN Lin2 & ZHONG ShiZhen2 1Department of Anatomy,Medical College of Jinan University,Guangzhou 510630,China 2Institute of Clinical Anatomy,Key Laboratory of Tissue Construction and Detection of Guangdong Province,Southern Medical University,Guangzhou 510150,China 1. Department of Anatomy Medical College of Jinan University Guangzhou 510630 China2. Institute of Clinical Anatomy Key Laboratory of Tissue Construction and Detection of Guangdong Province Southern Medical University Guangzhou 510150 China

Salvianolic acid B is isolated from Salvia miltiorrhiza,the root of which is widely used as a traditional Chinese medicine to treat ***,little is known about how salvianolic acid B influences growth characteristics of neural stem cells (NSCs).The purpose of the present study was to evaluate the effects of salvianolic acid B on proliferation,neurite outgrowth and differentiation of NSCs derived from the cerebral cortex of embryonic mice using MTT,flow cytometry,immunofluorescence and *** was found that 20 μg mL·1 and 40 μg mL·1 salvianolic acid B had similar effects on proliferation of NSCs,and a suitable concentration of salvianolic acid B increased the number of NSCs and their derivative *** growth-promoting activity of salvianolic acid B was dependent on and associated with an accumulation in the G2/S-phase cell *** acid B also promoted the neurite outgrowth of NSCs and their differentiation into *** mRNA for tau,GFAP and nestin were present in differentiating neurospheres induced by salvianolic acid ***,high-level expression of tau mRNA and low-level expression of GFAP mRNA was detected in differentiated cells,in contrast to the control *** collective evidence indicates that exogenous salvianolic acid B is capable of promoting proliferation of neurospheres and differentiation towards the neuronal lineage in vitro and may act in the proliferation of NSCs and may promote NSC differentiation into neuronal cells.

关键词： salvianolic acid B proliferation differentiation neurite outgrowth neural stem cells cerebral cortex embryonic mouse

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The　role　of　cell　surface　β1，　4－galactosyltransferase　duringectoplacentacone　outgrowth　on　laminin

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生殖医学杂志 1996年第S1期5卷 98-104页

作者：张春雨段恩奎曹宇靖曾国庆张春雨曹宇靖段恩奎曾国庆

Ｔｈｅｒｏｌｅｏｆｃｅｌｌｓｕｒｆａｃｅβ１，４－ｇａｌａｃｔｏｓｙｌｔｒａｎｓｆｅｒａｓｅｄｕｒｉｎｇｅｃｔｏｐｌａｃｅｎｔａｃｏｎｅｏｕｔｇｒｏｗｔｈ　ｏｎ　ｌａｍｉｎｉｎＺｈａｎｇＣｈｕｎｙｕ（张春雨），Ｃａｏ... 详细信息

Ｔｈｅｒｏｌｅｏｆｃｅｌｌｓｕｒｆａｃｅβ１，４－ｇａｌａｃｔｏｓｙｌｔｒａｎｓｆｅｒａｓｅｄｕｒｉｎｇｅｃｔｏｐｌａｃｅｎｔａｃｏｎｅｏｕｔｇｒｏｗｔｈ　ｏｎ　ｌａｍｉｎｉｎＺｈａｎｇＣｈｕｎｙｕ（张春雨），ＣａｏＹｕｊｉｎｇ（曹宇靖），ＤｕａｎＥ...

关键词： Ectoplacental cone β1,4-galactosyltransferase Attachment outgrowth Migration

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Enhancing Effect of Aged Garlic Extract on Induction of Morphological Differentiation with Neurite outgrowth in NGF-treated PC12 Cells

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Pharmacology & Pharmacy 2012年第1期3卷 37-43页

作者： Kohfuku Kohda Kei Itoh Hitomi Goda Keijiro Samejima Tomoko Fukuuchi Naoki Morihara Kazuhiko Imamura Yukihiro Kodera Takami Oka 不详

Background: We have been searching effective compounds that can stimulate the growth and differentiation of nerve cells. We found previously that fulleren derivatives enhanced induction of morphological differentiation with neurite outgrowth in nerve growth factor (NGF)-treated PC12 cells. In the course of our further search for other effective compounds, we found the aged garlic extract (AGE) has the activity similar to fulleren. Methods: PC12 cells were used to examine the effectiveness of test compound. Results: AGE enhanced the stimulating effect of NGF to induce morphological differentiation with neurite outgrowth in PC12 cells. In order to examine the active constituents of AGE, it was fractionated into several components. The activity was mainly localized in the F1 fraction that contains low molecular weight polar compounds. S-Allymercaptocysteine (SAMC) is one of the sulfur components of AGE present in F1 fraction and found to exhibit the enhancing effect similar to AGE. Conclusion: AGE had the ability to induce morphological differentiation with neurite outgrowth in NGF-treated PC12 cell and SAMC was one of its active constituents.

关键词： Aged Garlic Extract PC12 Cells NGF Differentiation Neurite outgrowth

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急性一氧化碳中毒致迟发性脑病大鼠胼胝体损伤及神经生长抑制因子A的表达

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中国急救医学 2014年第8期34卷 743-746,I0002页

作者：杨允王新春李林陆莹哈尔滨医科大学附属第二医院急诊科黑龙江哈尔滨150086

目的：研究急性一氧化碳（ carbon monoxide ， CO ）中毒致迟发性脑病（ delayed neuropsychologic sequelae ， DNS ）大鼠胼胝体的损伤及神经生长抑制因子 A （ neurite outgrowth inhibitor-A， Nogo-A）的表达情况。方法腹腔内分... 详细信息

目的：研究急性一氧化碳（ carbon monoxide ， CO ）中毒致迟发性脑病（ delayed neuropsychologic sequelae ， DNS ）大鼠胼胝体的损伤及神经生长抑制因子 A （ neurite outgrowth inhibitor-A， Nogo-A）的表达情况。方法腹腔内分次注射CO气体造成DNS模型，于不同时间点取胼胝体。HE染色观察细胞形态，变色酸染色观察脱髓鞘改变，免疫组化检测观察Nogo-A蛋白表达，荧光定量聚合酶链式反应（ real time polymerase chain reaction ， RT-PCR）检测Nogo-A mRNA表达，电镜观察胼胝体超微结构变化。结果中毒组光镜下胼胝体出现脱髓鞘等变化，以造模成功后0 h变化较明显。免疫组化显示，Nogo-A在各时间点均高表达（P＜0．05）。 RT-PCR于造模成功后0、12、24 h高表达（P＜0．05），0 h为高峰，其后逐渐下降，第3天与对照组比较差异无统计学意义，中毒组第7天表达再次升高（P＜0．05）。电镜下，胼胝体出现相应改变。结论 CO中毒后大鼠胼胝体出现脱髓鞘损伤，且与Nogo-A表达相关。

关键词：一氧化碳中毒迟发性脑病(DNS) 胼胝体脱髓鞘神经生长抑制因子A(Nogo-A) Delayed neuropsychologic sequelae (DNS) Neurite outgrowth inhibitor -A (Nogo-A)

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Angiogenesis and neuronal remodeling after ischemic stroke

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Neural Regeneration Research 2020年第1期15卷 16-19页

作者： Masahiro Hatakeyama Itaru Ninomiya Masato Kanazawa Department of Neurology Brain Research Institute Niigata University

Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal *** raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic *** vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a *** this mini-review,we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral *** occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and ***-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional ***,new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin ***,blood vessels are thought to enhance neurogenesis in three stages:1)Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals,2)microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen,nutrients,and soluble factors as well as serving as a scaffold for migration,and 3)oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature ***,the regions of angiogenesis and surrounding tissue may be coupled,representing novel treatment targets.

关键词： angiogenesis axonal outgrowth cerebral ischemia coupling functional recovery guidance neurogenesis stroke

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Role of miR-124 in the regulation of retinoic acid-induced Neuro-2A cell differentiation

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Neural Regeneration Research 2020年第6期15卷 1133-1139页

作者： Qun You Qiang Gong Yu-Qiao Han Rou Pi Yi-Jie Du Su-Zhen Dong Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghaiChina Department of Integrative Medicine Huashan HospitalFudan UniversityShanghaiChina Institutes of Integrative Medicine Fudan UniversityShanghaiChina

Retinoic acid can cause many types of cells,including mouse neuroblastoma Neuro-2 A cells,to differentiate into ***,it is still unknown whether microRNAs(miRNAs)play a role in this neuronal *** address this issue,real-time polymerase chain reaction assays were used to detect the expression of several differentiation-related miRNAs during the differentiation of retinoic acid-treated Neuro-2 A *** results revealed that miR-124 and miR-9 were upregulated,while miR-125 b was downregulated in retinoic acid-treated Neuro-2 A *** identify the miRNA that may play a key role,miR-124 expression was regulated by transfection of miRNA mimics or *** analysis results showed that inhibition of miR-124 expression reversed the effects of retinoic acid on neurite ***,miR-124 overexpression alone caused Neuro-2 A cells to differentiate into neurons,and its inhibitor could block this *** results suggest that miR-124 plays an important role in retinoic acid-induced differentiation of Neuro-2 A cells.

关键词： immunofluorescence MAP2 micro RNA mi R-124 Neuro-2A cells neurite outgrowth neuronal differentiation overexpression real-time PCR retinoic acid

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Pleiotrophin promotes perineural invasion in pancreatic cancer

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World Journal of Gastroenterology 2013年第39期19卷 6555-6558页

作者： Jun Yao Xiu-Feng Hu Xiao-Shan Feng She-Gan Gao Department of Oncology the First Affiliated Hospital of Henan University of Science and Technology

Perineural invasion(PNI)in pancreatic cancer is an important cause of local recurrence,but little is known about its ***(PTN)is an important neurotrophic *** is of interest that our recent experimental data showed its involvement in PNI of pancreatic *** strongly presents in the cytoplasm of pancreatic cancer cells,and high expression of PTN and its receptor may contribute to the high PNI of pancreatic ***,PNI is prone to happen in PTN-positive *** thus hypothesize that,as a neurite growth-promoting factor,PTN may promote PNI in pancreatic *** is released at the time of tumor cell necrosis,and binds with its highaffinity receptor,N-syndecan on pancreatic nerves,to promote neural growth in pancreatic ***,neural destruction leads to a distorted neural *** and Schwann cells produce more N-syndecan in an effort to repair the pancreatic ***,the abundance of N-syndecan attracts further PTN-positive cancer cells to the site of injury,creating a vicious ***,increased PTN and N-syndecan levels,due to the continuous nerve injury,may promote cancer invasion and propagation along the neural ***,it is meaningful to discuss the relationship between PTN/N-syndecan signaling and PNI in pancreatic cancer,which may lead to a better understanding of the mechanism of PNI in pancreatic cancer.

关键词： Pleiotrophin N-syndecan Neurite outgrowth Perineural invasion Pancreatic cancer

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