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TrkA regulates the regenerative capacity of bone marrow stromal stem cells in nerve grafts 预览
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作者 Mei-Ge Zheng Wen-Yuan Sui +8 位作者 Zhen-Dan He Yan Liu Yu-Lin Huang Shu-Hua Mu Xin-Zhong Xu Ji-Sen Zhang Jun-Le Qu Jian Zhang Dong Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第10期1765-1771,共7页
We previously demonstrated that overexpression of tropomyosin receptor kinase A(TrkA)promotes the survival and Schwann celllike differentiation of bone marrow stromal stem cells in nerve grafts,thereby enhancing the r... We previously demonstrated that overexpression of tropomyosin receptor kinase A(TrkA)promotes the survival and Schwann celllike differentiation of bone marrow stromal stem cells in nerve grafts,thereby enhancing the regeneration and functional recovery of the peripheral nerve.In the present study,we investigated the molecular mechanisms underlying the neuroprotective effects of TrkA in bone marrow stromal stem cells seeded into nerve grafts.Bone marrow stromal stem cells from Sprague-Dawley rats were infected with recombinant lentivirus vector expressing rat TrkA,TrkA-shRNA or the respective control.The cells were then seeded into allogeneic rat acellular nerve allografts for bridging a 1-cm right sciatic nerve defect.Then,8 weeks after surgery,hematoxylin and eosin staining showed that compared with the control groups,the cells and fibers in the TrkA overexpressing group were more densely and uniformly arranged,whereas they were relatively sparse and arranged in a disordered manner in the TrkA-shRNA group.Western blot assay showed that compared with the control groups,the TrkA overexpressing group had higher expression of the myelin marker,myelin basic protein and the axonal marker neurofilament 200.The TrkA overexpressing group also had higher levels of various signaling molecules,including TrkA,pTrkA(Tyr490),extracellular signal-regulated kinases 1/2(Erkl/2),pErk1/2(Thr202/Tyr204),and the anti-apoptotic proteins Bcl-2 and Bcl-xL.In contrast,these proteins were downregulated,while the pro-apoptotic factors Bax and Bad were upregulated,in the TrkA-shRNA group.The levels of the TrkA effectors Akt and pAkt(Ser473)were not different among the groups.These results suggest that TrkA enhances the survival and regenerative capacity of bone marrow stromal stem cells through upregulation of the Erk/Bcl-2 pathway.All procedures were approved by the Animal Ethical and Welfare Committee of Shenzhen University,China in December 2014(approval No.AEWC-2014-001219). 展开更多
关键词 NERVE REGENERATION bone marrow stromal stem cells TROPOMYOSIN RECEPTOR kinase A RECEPTOR LENTIVIRAL vector shRNA extracellular SIGNAL-REGULATED protein kinases 1/2 Bcl-2 NERVE grafts peripheral NERVE REGENERATION survival neural REGENERATION
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Novel miRNA,miR-sc14,promotes Schwann cell proliferation and migration 预览
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作者 Xi-Meng Ji Shan-Shan Wang +5 位作者 Xiao-Dong Cai Xing-Hui Wang Qian-Yan Liu Pan Wang Zhang-Chun Cheng Tian-Mei Qian 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第9期1651-1656,共6页
MicroRNAs refer to a class of endogenous,short non-coding RNAs that mediate numerous biological functions.MicroRNAs regulate various physiological and pathological activities of peripheral nerves,including peripheral ... MicroRNAs refer to a class of endogenous,short non-coding RNAs that mediate numerous biological functions.MicroRNAs regulate various physiological and pathological activities of peripheral nerves,including peripheral nerve repair and regeneration.Previously,using a rat sciatic nerve injury model,we identified many functionally annotated novel microRNAs,including miR-sc14.Here,we used real-time reverse transcription-polymerase chain reaction to examine miR-sc14 expression in rat sciatic nerve stumps.Our results show that miRsc14 is noticeably altered following sciatic nerve injury,being up-regulated at 1 day and diminished at 7 days.EdU and transwell chamber assay results showed that miR-sc14 mimic promoted proliferation and migration of Schwann cells,while miR-sc14 inhiThe study was approved by the Jiangsu Provincial Laboratory Animal Management Committee,China on March 4,2015(approval No.20150304-004).bitor suppressed their proliferation and migration.Additionally,bioinformatic analysis examined potential target genes of miR-sc14,and found that fibroblast growth factor receptor 2 might be a potential target gene.Specifically,our results show changes of miR-sc14 expression in the sciatic nerve of rats at different time points after nerve injury.Appropriately,up-regulation of miR-sc14 promoted proliferation and migration of Schwann cells.Consequently,miR-sc14 may be an intervention target to promote repair of peripheral nerve injury.The study was approved by the Jiangsu Provincial Laboratory Animal Management Committee,China on March 4,2015(approval No.20150304-004). 展开更多
关键词 NERVE REGENERATION novel microRNAs miR-sc14 PERIPHERAL NERVE injury cell PROLIFERATION cell MIGRATION Schwann cells fibroblast growth factor receptor 2 biological functions PERIPHERAL NERVE REGENERATION regulatory mechanisms neural REGENERATION
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Effect of lentiviral vector-mediated overexpression of hypoxia-inducible factor 1 alpha delivered by pluronic F-127 hydrogel on brachial plexus avulsion in rats 预览
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作者 Tao Wang Li-Ni Zeng +6 位作者 Zhe Zhu Yu-Hui Wang Lu Ding Wei-Bin Luo Xiao-Min Zhang Zhi-Wei He Hong-Fu Wu 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第6期1069-1078,共10页
Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles.However,no satisfactory treatment is currently available.Hypoxia-inducible factor 1αis a critical ... Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles.However,no satisfactory treatment is currently available.Hypoxia-inducible factor 1αis a critical molecule targeting several genes associated with ischemia-hypoxia damage and angiogenesis.In this study,a rat model of brachial plexus avulsion-reimplantation was established,in which C5–7 ventral nerve roots were avulsed and only the C6 root reimplanted.Different implants were immediately injected using a microsyringe into the avulsion-reimplantation site of the C6 root post-brachial plexus avulsion.Rats were randomly divided into five groups:phosphate-buffered saline,negative control of lentivirus,hypoxia-inducible factor 1α(hypoxia-inducible factor 1αoverexpression lentivirus),gel(pluronic F-127 hydrogel),and gel+hypoxia-inducible factor 1α(pluronic F-127 hydrogel+hypoxia-inducible factor 1αoverexpression lentivirus).The Terzis grooming test was performed to assess recovery of motor function.Scores were higher in the hypoxia-inducible factor 1αand gel+hypoxia-inducible factor 1αgroups(in particular the gel+hypoxia-inducible factor 1αgroup)compared with the phosphate-buffered saline group.Electrophysiology,fluorogold retrograde tracing,and immunofluorescent staining were further performed to investigate neural pathway reconstruction and changes of neurons,motor endplates,and angiogenesis.Compared with the phosphate-buffered saline group,action potential latency of musculocutaneous nerves was markedly shortened in the hypoxia-inducible factor 1αand gel+hypoxia-inducible factor 1αgroups.Meanwhile,the number of fluorogold-positive cells and ChAT-positive neurons,neovascular area(labeled by CD31 around av ulsed sites in ipsilateral spinal cord segments),and the number of motor endplates in biceps brachii(identified byα-bungarotoxin)were all visibly increased,as well as the morphology of motor endplate in biceps brachil was clear in the hypoxia-inducible factor 1αand gel+hypoxia-inducible f 展开更多
关键词 NERVE REGENERATION peripheral NERVE injury brachial plexus AVULSION HYPOXIA ischemia hypoxia-inducible factor 1αoverexpression PLURONIC F-127 motor neurons axonal REGENERATION angiogenesis neural REGENERATION
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Qian-Zheng-San promotes regeneration after sciatic nerve crush injury in rats 预览
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作者 Zhi-Yong Wang Li-Hua Qin +2 位作者 Wei-Guang Zhang Pei-Xun Zhang Bao-Guo Jiang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第4期683-691,共9页
Qian-Zheng-San,a traditional Chinese prescription consisting of Typhonii Rhizoma,Bombyx Batryticatus,Scorpio,has been found to play an active therapeutic role in central nervous system diseases.However,it is unclear w... Qian-Zheng-San,a traditional Chinese prescription consisting of Typhonii Rhizoma,Bombyx Batryticatus,Scorpio,has been found to play an active therapeutic role in central nervous system diseases.However,it is unclear whether Qian-Zheng-San has therapeutic value for peripheral nerve injury.Therefore,we used Sprague-Dawley rats to investigate this.A sciatic nerve crush injury model was induced by clamping the right sciatic nerve.Subsequently,rats in the treatment group were administered 2 mL Qian-Zheng-San(1.75 g/mL)daily as systemic therapy for 1,2,4,or 8 weeks.Rats in the control group were not administered Qian-Zheng-San.Rats in sham group did not undergo surgery and systemic therapy.Footprint analysis was used to assess nerve motor function.Electrophysiological experiments were used to detect nerve conduction function.Immunofluorescence staining was used to assess axon counts and morphological analysis.Immunohistochemical staining was used to observe myelin regeneration of the sciatic nerve and the number of motoneurons in the anterior horn of the spinal cord.At 2 and 4 weeks postoperatively,the sciatic nerve function index,nerve conduction velocity,the number of distant regenerated axons and the axon diameter of the sciatic nerve increased in the Qian-Zheng-San treatment group compared with the control group.At 2 weeks postoperatively,nerve fiber diameter,myelin thickness,and the number of motor neurons in the lumbar spinal cord anterior horn increased in the Qian-Zheng-San treatment group compared with the control group.These results indicate that Qian-Zheng-San has a positive effect on peripheral nerve regeneration. 展开更多
关键词 NERVE REGENERATION traditional Chinese medicine CRUSH INJURY peripheral NERVE REGENERATION NERVE conduction velocity SCIATIC function index NERVE INJURY NERVE repair formula SCORPION neural REGENERATION
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Endogenous automatic nerve discharge promotes nerve repair: an optimized animal model 预览
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作者 Jing Rui Ying-Jie Zhou +3 位作者 Xin Zhao Ji-Feng Li Yu-Dong Gu Jie Lao 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第2期306-312,共7页
Exogenous electrical nerve stimulation has been reported to promote nerve regeneration. Our previous study has suggested that endogenous automatic nerve discharge of the phrenic nerve and intercostal nerve has a posit... Exogenous electrical nerve stimulation has been reported to promote nerve regeneration. Our previous study has suggested that endogenous automatic nerve discharge of the phrenic nerve and intercostal nerve has a positive effect on nerve regeneration at 1 month postoperatively, but a negative effect at 2 months postoperatively, which may be caused by scar compression. In this study, we designed four different rat models to avoid the negative effect from scar compression. The control group received musculocutaneous nerve cut and repair. The other three groups were subjected to side-to-side transfer of either the phrenic (phrenic nerve group), intercostal (intercostal nerve group) or thoracodorsal nerves (thoracic dorsal nerve group), with sural nerve autograft distal to the anastomosis site. Musculocutaneous nerve regeneration was assessed by electrophysiology of the musculocutaneous nerve, muscle tension, muscle wet weight, maximum cross-sectional area of biceps, and myelinated fiber numbers of the proximal and distal ends of the anastomosis site of the musculocutaneous nerve and the middle of the nerve graft. At 1 month postoperatively, compound muscle action potential amplitude of the biceps in the phrenic nerve group and the intercostal nerve group was statistically higher than that in the control group. The myelinated nerve fiber numbers in the distal end of the musculocutaneous nerve and nerve graft anastomosis in the phrenic nerve and the intercostal nerve groups were statistically higher than those in the control and thoracic dorsal nerve groups. The neural degeneration rate in the middle of the nerve graft in the thoracic dorsal nerve group was statistically higher than that in the phrenic nerve and the intercostal nerve groups. At 2 and 3 months postoperatively, no significant difference was detected between the groups in all the assessments. These findings confirm that the phrenic nerve and intercostal nerve have a positive effect on nerve regeneration at the early stage of recovery. This study establish 展开更多
关键词 NERVE REGENERATION peripheral NERVE REGENERATION ENDOGENOUS AUTOMATIC DISCHARGE side-to-side NERVE anastomosis phrenic NERVE intercostal NERVE animal model electrical treatment rats NERVE compression neural REGENERATION
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Role and prospects of regenerative biomaterials in the repair of spinal cord injury 预览
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作者 Shuo Liu Yuan-Yuan Xie Bin Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第8期1352-1363,共12页
Axonal junction defects and an inhibitory environment after spinal cord injury seriously hinder the regeneration of damaged tissues and neuronal functions. At the site of spinal cord injury, regenerative biomaterials ... Axonal junction defects and an inhibitory environment after spinal cord injury seriously hinder the regeneration of damaged tissues and neuronal functions. At the site of spinal cord injury, regenerative biomaterials can fill cavities, deliver curative drugs, and provide adsorption sites for transplanted or host cells. Some regenerative biomaterials can also inhibit apoptosis, inflammation and glial scar formation, or further promote neurogenesis, axonal growth and angiogenesis. This review summarized a variety of biomaterial scaffolds made of natural, synthetic, and combined materials applied to spinal cord injury repair. Although these biomaterial scaffolds have shown a certain therapeutic effect in spinal cord injury repair, there are still many problems to be resolved, such as product standards and material safety and effectiveness. 展开更多
关键词 nerve REGENERATION spinal cord injury REGENERATIVE BIOMATERIALS scaffolds tissue engineering REGENERATION transplantation combination functional recovery REPAIR strategy MICROENVIRONMENT neural REGENERATION
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Soluble Nogo receptor 1 fusion protein protects neural progenitor cells in rats with ischemic stroke 预览
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作者 Hai-Wei He Yue-Lin Zhang +4 位作者 Bao-Qi Yu Gen Ye Wei You Kwok-fai So Xin Li 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第10期1755-1764,共10页
Soluble Nogo66 receptor-Fc protein(sNgR-Fc)enhances axonal regeneration following central nervous system injury.However,the underlying mechanisms remain unclear.In this study,we investigated the effects of sNgR-Fc on ... Soluble Nogo66 receptor-Fc protein(sNgR-Fc)enhances axonal regeneration following central nervous system injury.However,the underlying mechanisms remain unclear.In this study,we investigated the effects of sNgR-Fc on the proliferation and differentiation of neural progenitor cells.The photothrombotic cortical injury model of ischemic stroke was produced in the parietal cortex of Sprague-Dawley rats.The rats with photothrombotic cortical injury were randomized to receive infusion of 400μg/kg sNgR-Fc(sNgR-Fc group)or an equal volume of phosphate-buffered saline(photothrombotic cortical injury group)into the lateral ventricle for 3 days.The effects of sNgR-Fc on the proliferation and differentiation of endogenous neural progenitor cells were examined using BrdU staining.Neurological function was evaluated with the Morris water maze test.To further examine the effects of sNgR-Fc treatment on neural progenitor cells,photothrombotic cortical injury was produced in another group of rats that received transplantation of neural progenitor cells from the hippocampus of embryonic Sprague-Dawley rats.The animals were then given an infusion of phosphate-buffered saline(neural progenitor cells group)or sNgR-Fc(sNgR-Fc+neural progenitor cells group)into the lateral ventricle for 3 days.sNgR-Fc enhanced the proliferation of cultured neural progenitor cells in vitro as well as that of endogenous neural progenitor cells in vivo,compared with phosphate-buffered saline,and it also induced the differentiation of neural progenitor cells into neurons.Compared with the photothrombotic cortical injury group,escape latency in the Morris water maze and neurological severity score were greatly reduced,and distance traveled in the target quadrant was considerably increased in the sNgR-Fc group,indicating a substantial improvement in neurological function.Furthermore,compared with phosphate-buffered saline infusion,sNgR-Fc infusion strikingly improved the survival and differentiation of grafted neural progenitor cells.Our findings show that 展开更多
关键词 NEURAL REGENERATION Nogo-66 RECEPTOR Nogo66 receptor-Fc protein NEURAL PROGENITOR cells proliferation differentiation stroke photothrombotic cortical injury transplantation NEUROLOGICAL function nerve REGENERATION
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Eosinopenia is a predictive factor for the severity of acute ischemic stroke 预览
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作者 Hui-Min Zhao Wen-Qian Qin +1 位作者 Pei-Ji Wang Zhong-Min Wen 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第10期1772-1779,共8页
Previous data have revealed an association between eosinopenia and mortality of acute ischemic stroke.However,the relationship of eosinopenia with infarct volume,infection rate,and poor outcome of acute ischemic strok... Previous data have revealed an association between eosinopenia and mortality of acute ischemic stroke.However,the relationship of eosinopenia with infarct volume,infection rate,and poor outcome of acute ischemic stroke is still unknown.The retrospective study included 421 patients(273 males,65%;mean age,68.0± 13.0 years)with first acute ischemic stroke who were hospitalized in the Second Affiliated Hospital of Soochow University,China,from January 2017 to February 2018.Laboratory data,neuroimaging results,and modified Rankin Scale scores were collected.Patients were divided into four groups according to their eosinophil percentage level(<0.4%,0.4-1.1%,1 1-2.3%,≥2.3%).Spearman’s correlation analysis showed that the percentage of eosinophils was negatively correlated with infarct volume(rs=-0.514,P<0.001).Receiver operating characteristic analysis demonstrated that eosinopenia predicted a large infarct volume more accurately than neutrophilia;the area under curve was 0.906 and 0.876,respectively;a large infarct was considered as that with a diameter larger than 3 cm and involving more than two major arterial blood supply areas.Logistic regression analysis revealed that eosinophil percentage was an independent risk factor for acute ischemic stroke(P=0.002).Moreover,eosinophil percentage was significantly associated with large infarct volume,high infection rate(pulmonary and urinary tract infections),and poor outcome(modified Rankin Scale score>3)after adjusting for potential confounding factors(P-trend<0.001).These findings suggest that eosinopenia has the potential to predict the severity of acute ischemic stroke.This study was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University,China(approval number:K10)on November 10,2015. 展开更多
关键词 nerve REGENERATION eosinopenia EOSINOPHIL ISCHEMIA stroke INFARCT volume infection clinical outcome neutrophilia risk factors PREDICTIVE factor neural REGENERATION
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Collagen-chitosan scaffold impregnated with bone marrow mesenchymal stem cells for treatment of traumatic brain injury 预览
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作者 Feng Yan Ming Li +7 位作者 Hong-Qi Zhang Gui-Lin Li Yang Hua Ying Shen Xun-Ming Ji Chuan-Jie Wu Hong An Ming Ren 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第10期1780-1786,共7页
Combinations of biomaterials and cells can effectively target delivery of cells or other therapeutic factors to the brain to rebuild damaged nerve pathways after brain injury.Porous collagen-chitosan scaffolds were pr... Combinations of biomaterials and cells can effectively target delivery of cells or other therapeutic factors to the brain to rebuild damaged nerve pathways after brain injury.Porous collagen-chitosan scaffolds were prepared by a freeze-drying method based on brain tissue engineering.The scaffolds were impregnated with rat bone marrow mesenchymal stem cells.A traumatic brain injury rat model was established using the 300 g weight free fall impact method.Bone marrow mesenchymal stem cells/collagen-chitosan scaffolds were implanted into the injured brain.Modified neurological severity scores were used to assess the recovery of neurological function.The Morris water maze was employed to determine spatial learning and memory abilities.Hematoxylin-eosin staining was performed to measure pathological changes in brain tissue.Immunohistochemistry was performed for vascular endothelial growth factor and for 5-bromo-2-deoxyuridine(BrdU)/neuron specific enolase and BrdU/glial fibrillary acidic protein.Our results demonstrated that the transplantation of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds to traumatic brain injury rats remarkably reduced modified neurological severity scores,shortened the average latency of the Morris water maze,increased the number of platform crossings,diminished the degeneration of damaged brain tissue,and increased the positive reaction of vascular endothelial growth factor in the transplantation and surrounding areas.At 14 days after transplantation,increased BrdU/glial fibrillary acidic protein expression and decreased BrdU/neuron specific enolase expression were observed in bone marrow mesenchymal stem cells in the injured area.The therapeutic effect of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds was superior to stereotactic injection of bone marrow mesenchymal stem cells alone.To test the biocompatibility and immunogenicity of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds,immunosuppressive cyclosporine was intravenously inject 展开更多
关键词 nerve REGENERATION STEM CELLS COLLAGEN chitosan scaffolds traumatic BRAIN injury bone marrow mesenchymal STEM CELLS BRAIN tissue engineering neural REGENERATION
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Differences in pathological changes between two rat models of severe traumatic brain injury 预览
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作者 Yi-Ming Song Yu Qian +6 位作者 Wan-Qiang Su Xuan-Hui Liu Jin-Hao Huang Zhi-Tao Gong Hong-Liang Luo Chuang Gao Rong-Cai Jiang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第10期1796-1804,共9页
The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model u... The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters.In this study,we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences.The severe controlled cortical impact model was produced by an electronic controlled cortical impact device,while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube.Body temperature and mortality were recorded,and neurological deficits were assessed with the modified neurological severity score.Brain edema and bloodbrain barrier damage were evaluated by assessing brain water content and Evans blue extravasation.In addition,a cytokine array kit was used to detect inflammatory cytokines.Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining.Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations.More severe motor dysfunction was observed in the severe controlled cortical impact model,while more severe cognitive dysfunction was observed in the severe free weight drop model.Brain edema,inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group.The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage,with higher mortality and lower repeatability compared with the severe controlled cortical impact group.Severe brainstem damage was not found in the severe controlled cortical impact model.These results indicate that the severe controlled cortical impact model is relat 展开更多
关键词 nerve REGENERATION severe traumatic brain INJURY animal model comparison free weight drop controlled cortical impact NEUROLOGICAL impairment NEUROINFLAMMATION blood-brain barrier damage neuronal apoptosis diffuse AXONAL INJURY BRAINSTEM INJURY neural REGENERATION
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Brain networks modeling for studying the mechanism underlying the development of Alzheimer’s disease 预览
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作者 Shuai-Zong Si Xiao Liu +2 位作者 Jin-Fa Wang Bin Wang Hai Zhao 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第10期1805-1813,共9页
Alzheimer’s disease is a primary age-related neurodegenerative disorder that can result in impaired cognitive and memory functions.Although connections between changes in brain networks of Alzheimer’s disease patien... Alzheimer’s disease is a primary age-related neurodegenerative disorder that can result in impaired cognitive and memory functions.Although connections between changes in brain networks of Alzheimer’s disease patients have been established,the mechanisms that drive these alterations remain incompletely understood.This study,which was conducted in 2018 at Northeastern University in China,included data from 97 participants of the Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset covering genetics,imaging,and clinical data.All participants were divided into two groups:normal control(n=52;20 males and 32 females;mean age 73.90±4.72 years)and Alzheimer’s disease(n=45,23 males and 22 females;mean age 74.85±5.66).To uncover the wiring mechanisms that shaped changes in the topology of human brain networks of Alzheimer’s disease patients,we proposed a local naive Bayes brain network model based on graph theory.Our results showed that the proposed model provided an excellent fit to observe networks in all properties examined,including clustering coefficient,modularity,characteristic path length,network efficiency,betweenness,and degree distribution compared with empirical methods.This proposed model simulated the wiring changes in human brain networks between controls and Alzheimer’s disease patients.Our results demonstrate its utility in understanding relationships between brain tissue structure and cognitive or behavioral functions.The ADNI was performed in accordance with the Good Clinical Practice guidelines,US 21 CFR Part 50-Protection of Human Subjects,and Part 56-Institutional Review Boards(IRBs)/Research Good Clinical Practice guidelines Institutional Review Boards(IRBs)/Research Ethics Boards(REBs). 展开更多
关键词 nerve REGENERATION Alzheimer's disease graph theory functional magnetic resonance imaging network model link prediction NAIVE Bayes topological structures ANATOMICAL distance global EFFICIENCY local EFFICIENCY neural REGENERATION
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Ginsenoside Rb1 protects dopaminergic neurons from inflammatory injury induced by intranigral lipopolysaccharide injection 预览
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作者 Da-Wei Li Fa-Zhan Zhou +4 位作者 Xian-Chang Sun Shu-Chen Li Jin-Bin Yang Huan-Huan Sun Ai-Hua Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第10期1814-1822,共9页
Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be ... Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be a promising treatment strategy to delay the onset or slow the progression of Parkinson’s disease.Ginsenoside Rbl,the most active ingredient of ginseng,reportedly exerts neuroprotective effects by suppressing inflammation in vitro.The present study aimed to evaluate the neuroprotective and anti-inflammatory effects of ginsenoside Rbl in a lipopolysaccharide-induced rat Parkinson’s disease model.Rats were divided into four groups.In the control group,sham-operated rats were intraperitoneally administered normal saline for 14 consecutive days.In the ginsenoside Rbl group,ginsenoside Rb1(20 mg/kg)was intraperitoneally injected for 14 consecutive days after sham surgery.In the lipopolysaccharide group,a single dose of lipopolysaccharide was unilaterally microinjected into the rat substantial nigra to establish the Parkinson’s disease model.Lipopolysaccharide-injected rats were treated with normal saline for 14 consecutive days.In the ginsenoside Rbl +lipopolysaccharide group,lipopolysaccharide was unilaterally microinjected into the rat substantial nigra.Subsequently,ginsenoside Rbl was intraperitoneally injected for 14 consecutive days.To investigate the therapeutic effects of ginsenoside Rbl,behavioral tests were performed on day 15 after lipopolysaccharide injection.We found that ginsenoside Rbl treatment remarkably reduced apomorphine-induced rotations in lipopolysaccharide-treated rats compared with the lipopolysaccharide group.To investigate the neurotoxicity of lipopolysaccharide and potential protective effect of ginsenoside Rbl,contents of dopamine and its metabolites in the striatum were measured by high-performance liquid chromatography.Compared with the lipopolysaccharide group,ginsenoside Rbl obviously attenuated the lipopolysaccharide-induced depletion of dopamine and its metabolites 展开更多
关键词 nerve REGENERATION NEURODEGENERATION Parkinson's disease GINSENOSIDE Rb1 neuroinflammation LIPOPOLYSACCHARIDE DOPAMINERGIC neuron microglia nuclear factor kappa B dopamine tyrosine HYDROXYLASE substantia nigra neural REGENERATION
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Mapping theme trends and knowledge structures for human neural stem cells:a quantitative and co-word biclustering analysis for the 2013-2018 period 预览
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作者 Wen-Juan Wei Bei Shi +3 位作者 Xin Guan Jing-Yun Ma Ya-Chen Wang Jing Liu 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第10期1823-1832,共10页
Neural stem cells,which are capable of multi-potential differentiation and self-renewal,have recently been shown to have clinical potential for repairing central nervous system tissue damage.However,the theme trends a... Neural stem cells,which are capable of multi-potential differentiation and self-renewal,have recently been shown to have clinical potential for repairing central nervous system tissue damage.However,the theme trends and knowledge structures for human neural stem cells have not yet been studied bibliometrically.In this study,we retrieved 2742 articles from the PubMed database from 2013 to 2018 using "Neural Stem Cells" as the retrieval word.Co-word analysis was conducted to statistically quantify the characteristics and popular themes of human neural stem cell-related studies.Bibliographic data matrices were generated with the Bibliographic Item Co-Occurrence Matrix Builder.We identified 78 high-frequency Medical Subject Heading(MeSH)terms.A visual matrix was built with the repeated bisection method in gCLUTO software.A social network analysis network was generated with Ucinet 6.0 software and GraphPad Prism 5 software.The analyses demonstrated that in the 6-year period,hot topics were clustered into five categories.As suggested by the constructed strategic diagram,studies related to cytology and physiology were well-developed,whereas those related to neural stem cell applications,tissue engineering,metabolism and cell signaling,and neural stem cell pathology and virology remained immature.Neural stem cell therapy for stroke and Parkinson’s disease,the genetics of microRNAs and brain neoplasms,as well as neuroprotective agents,Zika virus,Notch receptor,neural crest and embryonic stem cells were identified as emerging hot spots.These undeveloped themes and popular topics are potential points of focus for new studies on human neural stem cells. 展开更多
关键词 nerve REGENERATION human NEURAL stem cells PubMed bibliometric ANALYSIS biclustering ANALYSIS co-word ANALYSIS strategic diagram ANALYSIS social network ANALYSIS hot research topics MAPPING THEME TRENDS knowledge structures NEURAL REGENERATION
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MGMT is down-regulated independently of promoter DNA methylation in rats with all-trans retinoic acidinduced spina bifida aperta 预览
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作者 He-Nan Zhang Yi Guo +3 位作者 Wei Ma Jia Xue Wei-Lin Wang Zheng-Wei Yuan 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第2期361-368,共8页
O6-methylguanine DNA methyltransferase (MGMT), a DNA repair enzyme, has been reported in some congenital malformations, but it is less frequently reported in neural tube defects. This study investigated MGMT mRNA expr... O6-methylguanine DNA methyltransferase (MGMT), a DNA repair enzyme, has been reported in some congenital malformations, but it is less frequently reported in neural tube defects. This study investigated MGMT mRNA expression and methylation levels in the early embryo and in different embryonic stages, as well as the relationship between MGMT and neural tube defects. Spina bifida aperta was induced in rats by a single intragastric administration of all-trans retinoic acid on embryonic day (E) 10, whereas normal control rats received the same amount of olive oil on the same embryonic day. DNA damage was assessed by detecting γ-H2A.X in spina bifida aperta rats. Real time-polymerase chain reaction was used to examine mRNA expression of MGMT in normal control and spina bifida aperta rats. In normal controls, the MGMT mRNA expression decreased with increasing embryonic days, and was remarkably reduced from E11 to E14, reaching a minimum at E18. In the spina bifida aperta model, γ-H2A.X protein expression was increased, and mRNA expression of MGMT was markedly decreased on E14, E16, and E18. Bisulfite sequencing polymerase chain reaction for MGMT promoter methylation demonstrated that almost all CpG sites in the MGMT promoter remained unmethylated in both spina bifida aperta rats and normal controls, and there was no significant difference in methylation level between the two groups on either E14 or E18. Our results show that DNA damage occurs in spina bifida aperta rats. The mRNA expression of MGMT is downregulated, and this downregulation is independent of promoter DNA methylation. 展开更多
关键词 nerve REGENERATION NEURAL tube defects spina bifida aperta spinal cord ALL-TRANS retinoic acid O6-methylguanine DNA methyltransferase gene expression DNA methylation PROMOTER BISULFITE sequencing polymerase chain reaction NEURAL REGENERATION
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Decreased numbers of circulating endothelial progenitor cells are associated with hyperglycemia in patients with traumatic brain injury 预览
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作者 Hui-Jie Wei Li Liu +7 位作者 Fang-Lian Chen Dong Wang Liang Wang Zeng-Guang Wang Rong-Cai Jiang Jing-Fei Dong Jie-Li Chen Jian-Ning Zhang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第6期984-990,共7页
Hyperglycemia reduces the number of circulating endothelial progenitor cells,accelerates their senescence and impairs their function.However,the relationship between blood glucose levels and endothelial progenitor cel... Hyperglycemia reduces the number of circulating endothelial progenitor cells,accelerates their senescence and impairs their function.However,the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear.In this study,101 traumatic brain injury patients admitted to the Department of Neurosurgery,Tianjin Medical University General Hospital or the Department of Neurosurgery,Tianjin Huanhu Hospital,China,were enrolled from April 2005 to March 2007.The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1,4,7,14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis,respectively.The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined.Compared with controls,the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury,and then increased at 4 days after injury,and reached a peak at 7 days after injury.Compared with controls,blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable.At 1,4,and 7 days after injury,the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r=?0.147,P<0.05).Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells.This study was approved by the Ethical Committee of Tianjin Medical University General Hospital,China(approval No.200501)in January 2015. 展开更多
关键词 nerve REGENERATION endothelial progenitor cells VASCULAR repair VASCULAR remodeling angiogenesis NEOVASCULARIZATION blood glucose HYPERGLYCEMIA traumatic BRAIN injury MOBILIZATION suppression senescence alternative therapy BRAIN damage neural REGENERATION
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Neurological functional evaluation based on accurate motions in big animals with traumatic brain injury 预览
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作者 Ji-Peng Jiang Xue-Gang Niu +9 位作者 Chen Dai Ke Ma Hui-You Xu Shi-Xiang Cheng Zhi-Wen Zhang Feng Duan Xu Zhu Yu-Ting Wang Xu-Yi Chen Sai Zhang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第6期991-996,共6页
An accurate and effective neurological evaluation is indispensable in the treatment and rehabilitation of traumatic brain injury.However,most of the existing evaluation methods in basic research and clinical practice ... An accurate and effective neurological evaluation is indispensable in the treatment and rehabilitation of traumatic brain injury.However,most of the existing evaluation methods in basic research and clinical practice are not objective or intuitive for assessing the neurological function of big animals,and are also difficult to use to qualify the extent of damage and recovery.In the present study,we established a big animal model of traumatic brain injury by impacting the cortical motor region of beagles.At 2 weeks after successful modeling,we detected neurological deficiencies in the animal model using a series of techniques,including three-dimensional motion capture,electromyogram and ground reaction force.These novel technologies may play an increasingly important role in the field of traumatic brain injury diagnosis and rehabilitation in the future.The experimental protocol was approved by the Animal Care and Use Committee of Logistics University of People’s Armed Police Force(approval No.2017-0006.2). 展开更多
关键词 nerve REGENERATION evaluation method NEUROLOGICAL deficiency TRAUMATIC brain injury motion capture ELECTROMYOGRAM ground reaction force neural REGENERATION
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Association between PPARG genetic polymorphisms and ischemic stroke risk in a northern Chinese Han population: a case-control study 预览
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作者 Yan-Zhe Wang He-Yu Zhang +3 位作者 Fang Liu Lei Li Shu-Min Deng Zhi-Yi He 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第11期1986-1993,共8页
Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-co... Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012(approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group(P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke(OR = 1.844, 95% CI: 1.286–2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke(OR = 1.366, 95% CI: 1.077–1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in 展开更多
关键词 nerve REGENERATION STROKE cerebral ischemia ISCHEMIC STROKE PEROXISOME proliferator-activated receptor γ single-nucleotide polymorphism haplotype analysis interaction CASE-CONTROL study Chinese Han population neural REGENERATION
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Atsttrin reduces lipopolysaccharide-induced neuroinflammation by inhibiting the nuclear factor kappa B signaling pathway 预览
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作者 Lian Liu Yuan Qu +7 位作者 Yi Liu Hua Zhao He-Cheng Ma Ahmed Fayyaz Noor Chang-Jiao Ji Lin Nie Meng Si Lei Cheng 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第11期1994-2002,共9页
Progranulin is closely related to neuronal survival in a neuroinflammatory mouse model and attenuates inflammatory reactions. Atsttrin is an engineered protein composed of three progranulin fragments and has been show... Progranulin is closely related to neuronal survival in a neuroinflammatory mouse model and attenuates inflammatory reactions. Atsttrin is an engineered protein composed of three progranulin fragments and has been shown to have an effect similar to that of progranulin. Atsttrin has anti-inflammatory actions in multiple arthritis mouse models, and it protects against further arthritis development. However, whether Atsttrin has a role in neuroinflammation remains to be elucidated. In this study, we produced a neuroinflammatory mouse model by intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). Atsttrin(2.5 mg/kg) was administered via intraperitoneal injection every 3 days over a period of 7 days before intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). In addition, astrocyte cultures were treated with 0, 100 or 300 ng/mL lipopolysaccharide, with 200 ng/mL Atsttrin simultaneously. Immunohistochemistry, enzyme-linked immunosorbent assay and real-time reverse transcription-polymerase chain reaction were performed to examine the protein and mRNA levels of inflammatory mediators and to assess activation of the nuclear factor kappa B signaling pathway. Progranulin expression in the brain of wild-type mice and in astrocyte cultures was increased after lipopolysaccharide administration. The protein and mRNA expression levels of tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were increased in the brain of progranulin knockout mice after lipopolysaccharide administration. Atsttrin treatment reduced the lipopolysaccharide-induced increase in the protein and mRNA levels of tumor necrosis factor-α, interleukin-1β, matrix metalloproteinase-3 and inducible nitric oxide synthase in the brain of progranulin knockout mice. Atsttrin also reduced the expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase 3 mRNA in lipopolysaccharide-treated astrocytes in vitro, and decreased the concentration of tumor necrosis factor α 展开更多
关键词 nerve REGENERATION progranulin Atsttrin NEUROINFLAMMATION inflammatory cytokines LIPOPOLYSACCHARIDE INTRACEREBROVENTRICULAR injection ASTROCYTE nuclear factor kappa B signaling pathway progranulin knockout mouse CEREBROSPINAL fluid neural REGENERATION
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MicroRNA expression in the hippocampal CA1 region under deep hypothermic circulatory arrest 预览
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作者 Xiao-Hua Wang Dong-Xu Yao +7 位作者 Xiu-Shu Luan Yu Wang Hai-Xia Liu Bei Liu Yang Liu Lei Zhao Xun-Ming Ji Tian-Long Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第11期2003-2010,共8页
Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulat... Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulatory arrest are unclear. After piglet models underwent 60 minutes of deep hypothermic circulatory arrest at 14°C, expression of microRNAs(miRNAs) was analyzed in the hippocampus by microarray. Subsequently, TargetScan 6.2, RNA22 v2.0, miRWalk 2.0, and miRanda were used to predict potential targets, and gene ontology enrichment analysis was carried out to identify functional pathways involved. Quantitative reverse transcription-polymerase chain reaction was conducted to verify miRNA changes. Deep hypothermic circulatory arrest altered the expression of 35 miRNAs. Twenty-two miRNAs were significantly downregulated and thirteen miRNAs were significantly upregulated in the hippocampus after deep hypothermic circulatory arrest. Six out of eight targets among the differentially expressed miRNAs were enriched for neuronal projection(cyclin dependent kinase, CDK16 and SLC1 A2), central nervous system development(FOXO3, TYRO3, and SLC1 A2), ion transmembrane transporter activity(ATP2 B2 and SLC1 A2), and interleukin-6 receptor binding(IL6 R)– these are the key functional pathways involved in cerebral protection during deep hypothermic circulatory arrest. Quantitative reverse transcription-polymerase chain reaction confirmed the results of microarray analysis. Our experimental results illustrate a new role for transcriptional regulation in deep hypothermic circulatory arrest, and provide significant insight for the development of miRNAs to treat brain injuries. All procedures were approved by the Animal Care Committee of Xuanwu Hospital, Capital Medical University, China on March 1, 2017(approval No. XW-INI-AD2017-0112). 展开更多
关键词 nerve REGENERATION cerebral protection deep hypothermic circulatory ARREST gene ontology enrichment analysis microRNA hippocampus POST-TRANSCRIPTIONAL expression MICROARRAY BIOINFORMATICS neural REGENERATION
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Etomidate affects the anti-oxidant pathway to protect retinal ganglion cells after optic nerve transection 预览
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作者 Xuan Zhao Fang Kuang +2 位作者 Yi-Yan You Ming-Mei Wu Si-Wei You 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第11期2020-2024,共5页
Our previous studies revealed that etomidate, a non-barbiturate intravenous anesthetic agent, has protective effects on retinal ganglion cells within 7 days after optic nerve transection. Whether this process is relat... Our previous studies revealed that etomidate, a non-barbiturate intravenous anesthetic agent, has protective effects on retinal ganglion cells within 7 days after optic nerve transection. Whether this process is related to anti-oxidative stress is not clear. To reveal its mechanism, we established the optic nerve transection injury model by transecting 1 mm behind the left eyeball of adult male Sprague-Dawley rats. The rats received an intraperitoneal injection of etomidate(4 mg/kg) once per day for 7 days. The results showed that etomidate significantly enhanced the number of retinal ganglion cells retrogradely labeled with Fluorogold at 7 days after optic nerve transection. Etomidate also significantly reduced the levels of nitric oxide and malonaldehyde in the retina and increased the level of glutathione at 12 hours after optic nerve transection. Thus, etomidate can protect retinal ganglion cells after optic nerve transection in adult rats by activating an anti-oxidative stress response. The study was approved by the Animal Ethics Committee at Air Force Medical University, China(approval No. 20180305) on March 5, 2018. 展开更多
关键词 NERVE REGENERATION ETOMIDATE retinal ganglion cells optic NERVE TRANSECTION anti-oxidative stress nitric oxide MALONALDEHYDE glutathione neural REGENERATION
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