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Effects of neural stem cell transplantation on the motor function of rats with contusion spinal cord injuries:a meta-analysis 预览
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作者 Kai Qian Tuo-Ye Xu +7 位作者 Xi Wang Tao Ma Kai-Xin Zhang Kun Yang Teng-Da Qian Jing Shi Li-Xin Li Zheng Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期748-758,共11页
Objective:To judge the efficacies of neural stem cell(NSC)transplantation on functional recovery following contusion spinal cord injuries(SCIs).Data sources:Studies in which NSCs were transplanted into a clinically re... Objective:To judge the efficacies of neural stem cell(NSC)transplantation on functional recovery following contusion spinal cord injuries(SCIs).Data sources:Studies in which NSCs were transplanted into a clinically relevant,standardized rat model of contusion SCI were identified by searching the PubMed,Embase and Cochrane databases,and the extracted data were analyzed by Stata 14.0.Data selection:Inclusion criteria were that NSCs were used in in vivo animal studies to treat contusion SCIs and that behavioral assessment of locomotor functional recovery was performed using the Basso,Beattie,and Bresnahan lo-comotor rating scale.Exclusion criteria included a follow-up of less than 4 weeks and the lack of control groups.Outcome measures:The restoration of motor function was assessed by the Basso,Beattie,and Bresnahan locomotor rating scale.Results:We identified 1756 non-duplicated papers by searching the aforementioned electronic databases,and 30 full-text articles met the inclusion criteria.A total of 37 studies reported in the 30 articles were included in the meta-analysis.The meta-analysis results showed that transplanted NSCs could improve the motor function recovery of rats following contusion SCIs,to a moderate extent(pooled standardized mean difference(SMD)=0.73;95%confidence interval(CI):0.47–1.00;P<0.001).NSCs obtained from different donor species(rat:SMD=0.74;95%CI:0.36–1.13;human:SMD=0.78;95%CI:0.31–1.25),at different donor ages(fetal:SMD=0.67;95%CI:0.43–0.92;adult:SMD=0.86;95%CI:0.50–1.22)and from different origins(brain-derived:SMD=0.59;95%CI:0.27–0.91;spinal cord-derived:SMD=0.51;95%CI:0.22–0.79)had similar efficacies on improved functional recovery;however,adult induced pluripotent stem cell-derived NSCs showed no significant efficacies.Furthermore,the use of higher doses of transplanted NSCs or the administration of immunosuppressive agents did not promote better locomotor function recovery(SMD=0.45;95%CI:0.21–0.70).However,shorter periods between the contusion induction and the NSC tr 展开更多
关键词 Basso Beattie and Bresnahan locomotor rating scale CELL TRANSPLANTATION META-ANALYSIS motor functional recovery NEURAL regeneration NEURAL stem CELL NEURAL stem CELL TRANSPLANTATION rat model SPINAL CONTUSION SPINAL cord injury
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Extracellular matrix and biomimetic engineering microenvironment for neuronal differentiation 预览
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作者 Deepak Jain Sabrina Mattiassi +1 位作者 Eyleen L.Goh Evelyn K.F.Yim 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期573-585,共13页
Extracellular matrix(ECM)influences cell differentiation through its structural and biochemical properties.In nervous system,neuronal behavior is influenced by these ECMs structures which are present in a meshwork,fib... Extracellular matrix(ECM)influences cell differentiation through its structural and biochemical properties.In nervous system,neuronal behavior is influenced by these ECMs structures which are present in a meshwork,fibrous,or tubular forms encompassing specific molecular compositions.In addition to contact guidance,ECM composition and structures also exert its effect on neuronal differentiation.This short report reviewed the native ECM structure and composition in central nervous system and peripheral nervous system,and their impact on neural regeneration and neuronal differentiation.Using topographies,stem cells have been differentiated to neurons.Further,focussing on engineered biomimicking topographies,we highlighted the role of anisotropic topographies in stem cell differentiation to neurons and its recent temporal application for efficient neuronal differentiation. 展开更多
关键词 BIOMIMETIC platforms biophysical cues contact guidance extracellular matrix NEURONAL development NEURAL regeneration NEURAL STEM CELL niche NEURONAL differentiation NEURONAL maturation STEM CELL topography
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Heterogeneity in the regenerative abilities of central nervous system axons within species:why do some neurons regenerate better than others? 预览
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作者 William Rodemer Jianli Hu +1 位作者 Michael E.Selzer Michael I.Shifman 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第6期996-1005,共10页
Some neurons,especially in mammalian peripheral nervous system or in lower vertebrate or in vertebrate central nervous system(CNS)regenerate after axotomy,while most mammalian CNS neurons fail to regenerate.There is a... Some neurons,especially in mammalian peripheral nervous system or in lower vertebrate or in vertebrate central nervous system(CNS)regenerate after axotomy,while most mammalian CNS neurons fail to regenerate.There is an emerging consensus that neurons have different intrinsic regenerative capabilities,which theoretically could be manipulated therapeutically to improve regeneration.Population-based comparisons between"good regenerating"and"bad regenerating"neurons in the CNS and peripheral nervous system of most vertebrates yield results that are inconclusive or difficult to interpret.At least in part,this reflects the great diversity of cells in the mammalian CNS.Using mammalian nervous system imposes several methodical limitations.First,the small sizes and large numbers of neurons in the CNS make it very difficult to distinguish regenerating neurons from non-regenerating ones.Second,the lack of identifiable neurons makes it impossible to correlate biochemical changes in a neuron with axonal damage of the same neuron,and therefore,to dissect the molecular mechanisms of regeneration on the level of single neurons.This review will survey the reported responses to axon injury and the determinants of axon regeneration,emphasizing non-mammalian model organisms,which are often under-utilized,but in which the data are especially easy to interpret. 展开更多
关键词 axonal regeneration identifiable neurons intrinsic factors LAMPREY Mauthner cell Müller cell neuronal death non-mammalian model organisms spinal cord injury zebrafish
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Alzheimer’s disease, neural stem cells and neurogenesis:cellular phase at single-cell level 预览
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作者 Mehmet Ilyas Cosacak Prabesh Bhattarai Caghan Kizil 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期824-827,共4页
Alzheimer’s disease cannot be cured as of yet.Our current understanding on the causes of Alzheimer’s disease is limited.To develop treatments,experimental models that represent a particular cellular phase of the dis... Alzheimer’s disease cannot be cured as of yet.Our current understanding on the causes of Alzheimer’s disease is limited.To develop treatments,experimental models that represent a particular cellular phase of the disease and more rigorous scrutiny of the cellular pathological mechanisms are crucial.In recent years,Alzheimer’s disease research underwent a paradigm shift.According to this tendency,Alzheimer’s disease is increasingly being conceived of a disease where not only neurons but also multiple cell types synchronously partake to manifest the pathology.Knowledge on every cell type adds an alternative approach and hope for the efforts towards the treatment.Neural stem cells and their neurogenic ability are making an appearance as a new aspect of the disease manifestation based on the recent findings that neurogenesis reduces dramatically in Alzheimer’s disease patients compared to healthy individuals.Therefore,understanding how neural stem cells can form new neurons in Alzheimer’s disease brains holds an immense potential for clinics.However,this provocative idea requires further evidence and tools for investigation.Recently,single cell sequencing appeared as a revolutionary tool to understand cellular programs in unprecedented resolution and it will undoubtedly facilitate comprehensive investigation of different cell types in Alzheimer’s disease.In this mini-review,we will touch upon recent studies that use single cell sequencing for investigating cellular response in Alzheimer’s disease and some consideration pertaining to the utilization of neural regeneration for Alzheimer’s disease research. 展开更多
关键词 Alzheimer's disease mouse NEURAL regeneration NEURAL stem CELL NEUROGENESIS neuron single CELL sequencing ZEBRAFISH
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Differential expression of glial cell line-derived neurotrophic factor splice variants in the mouse brain 预览
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作者 Xiao-He Gu Heng Li +4 位作者 Lin Zhang Tao He Xiang Chai He Wei Dian-Shuai Gao 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期270-276,共7页
Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neu... Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the GDNF splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α-and β-pro-GDNF in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level,β-pro-GDNF expression was significantly greater than that of α-pro-GDNF in the mouse brain. In contrast, at the protein level,α-pro-GDNF expression was markedly greater than that of β-pro-GDNF. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the GDNF splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats(SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-GDNF expression, but not with α-pro-GDNF expression. This suggests that the differential expression of α-and β-pro-GDNF in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the GDNF isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016. 展开更多
关键词 Δ78 locus BRAIN region dopaminergic neurons glial cell line-derived NEUROTROPHIC factor mouse BRAIN precursor protein α-pro-GDNF β-pro-GDNF sorting protein-related receptor with A-TYPE REPEATS splice variants
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Neuroprotective mechanism of TMP269, a selective class ⅡA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury 预览
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作者 Lu Su Dan Liang +3 位作者 Shen-Yi Kuang Qiang Dong Xiang Han Zheng Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期277-284,共8页
TMP269 is a selective class ⅡA histone deacetylase inhibitor that has a protective effect on the central nervous system, whose specific mechanism of action is unclear. We aimed to reveal the optimal concentration of ... TMP269 is a selective class ⅡA histone deacetylase inhibitor that has a protective effect on the central nervous system, whose specific mechanism of action is unclear. We aimed to reveal the optimal concentration of TMP269 for protecting against cerebral ischemia/reperfusion injury and its neuroprotective mechanism. Male Sprague-Dawley rats were randomly divided into sham, ischemia/reperfusion, and 1, 4, 10 and 16 mg/kg TMP269 groups. Cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. TMP269 was intraperitoneally administered at different doses 0.5 hours before ischemia induction. Western blot assay and immunohistochemistry were used to detect effects of TMP269 on histone 2 acetylation. The results showed that the level of histone 2 acetylation was increased 24 hours after TMP269 injection. 2,3,5-Triphenyltetrazolium chloride staining was utilized to examine effect of TMP269 on infarct volume. The results found that different doses of TMP269 could reduce the infarct volume. Western blot assay, immunohistochemistry and Evans blue staining were employed to measure the effect of TMP269 on blood-brain barrier. The results showed that TMP269 counteracted the abnormal endothelial cell permeability changes caused by cerebral ischemia/reperfusion. Western blot assay and immunohistochemistry were used to determine the effect of TMP269 on tissue kallikrein. The results found that TMP269 up-regulated the expression of tissue kallikrein. Western blot assay further determined the optimal concentration to be 4 mg/kg. In conclusion, TMP269 plays a neuroprotective role by up-regulating the level of histone 2 acetylation, alleviating endothelial cell injury after cerebral ischemia/reperfusion, and up-regulating the expression of tissue kallikrein. The experimental protocol was approved in 2014 by the Department of Laboratory Animal Science, Fudan University, China(approval No. 20140143 C001). 展开更多
关键词 blood-brain barrier drug treatment endothelial cell permeability HISTONE DEACETYLASE inhibitor NEUROPROTECTION stroke tissue KALLIKREIN TMP269
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Remnant neuromuscular junctions in denervated muscles contribute to functional recovery in delayed peripheral nerve repair 预览
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作者 Leyang Li Hiroyuki Yokoyama +5 位作者 Hidetoshi Kaburagi Takashi Hirai Kunikazu Tsuji Mitsuhiro Enomoto Yoshiaki Wakabayashi Atsushi Okawa 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期731-738,共8页
Schwann cell proliferation in peripheral nerve injury(PNI)enhances axonal regeneration compared to central nerve injury.However,even in PNI,long-term nerve damage without repair induces degeneration of neuromuscular j... Schwann cell proliferation in peripheral nerve injury(PNI)enhances axonal regeneration compared to central nerve injury.However,even in PNI,long-term nerve damage without repair induces degeneration of neuromuscular junctions(NMJs),and muscle atrophy results in irreversible dysfunction.The peripheral regeneration of motor axons depends on the duration of skeletal muscle denervation.To overcome this difficulty in nerve regeneration,detailed mechanisms should be determined for not only Schwann cells but also NMJ degeneration after PNI and regeneration after nerve repair.Here,we examined motor axon denervation in the tibialis anterior muscle after peroneal nerve transection in thy1-YFP mice and regeneration with nerve reconstruction using allografts.The number of NMJs in the tibialis anterior muscle was maintained up to 4 weeks and then decreased at 6 weeks after injury.In contrast,the number of Schwann cells showed a stepwise decline and then reached a plateau at 6 weeks after injury.For regeneration,we reconstructed the degenerated nerve with an allograft at 4 and 6 weeks after injury,and evaluated functional and histological outcomes for 10 to 12 weeks after grafting.A higher number of pretzel-shaped NMJs in the tibialis anterior muscle and better functional recovery were observed in mice with a 4-week delay in surgery than in those with a 6-week delay.Nerve repair within 4 weeks after PNI is necessary for successful recovery in mice.Prevention of synaptic acetylcholine receptor degeneration may play a key role in peripheral nerve regeneration.All animal experiments were approved by the Institutional Animal Care and Use Committee of Tokyo Medical and Dental University on 5 July 2017,30 March 2018,and 15 May 2019(A2017-311C,A2018-297A,and A2019-248A),respectively. 展开更多
关键词 AXON NERVE ALLOGRAFT NERVE regeneration NEURODEGENERATION NEUROMUSCULAR junction peripheral NERVE injury Schwann cell skeletal muscle
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Differential neuronal reprogramming induced by NeuroD1 from astrocytes in grey matter versus white matter 预览
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作者 Min-Hui Liu Wen Li +3 位作者 Jia-Jun Zheng Yu-Ge Xu Qing He Gong Chen 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期342-351,共10页
A new technology called in vivo glia-to-neuron conversion has emerged in recent years as a promising next generation therapy for neural regeneration and repair. This is achieved through reprogramming endogenous glial ... A new technology called in vivo glia-to-neuron conversion has emerged in recent years as a promising next generation therapy for neural regeneration and repair. This is achieved through reprogramming endogenous glial cells into neurons in the central nervous system through ectopically expressing neural transcriptional factors in glial cells. Previous studies have been focusing on glial cells in the grey matter such as the cortex and striatum, but whether glial cells in the white matter can be reprogrammed or not is unknown. To address this fundamental question, we express NeuroD1 in the astrocytes of both grey matter(cortex and striatum) and white matter(corpus callosum) to investigate the conversion efficiency, neuronal subtypes, and electrophysiological features of the converted neurons. We discover that NeuroD1 can efficiently reprogram the astrocytes in the grey matter into functional neurons, but the astrocytes in the white matter are much resistant to neuronal reprogramming. The converted neurons from cortical and striatal astrocytes are composed of both glutamatergic and GABAergic neurons, capable of firing action potentials and having spontaneous synaptic activities. In contrast, the few astrocyte-converted neurons in the white matter are rather immature with rare synaptic events. These results provide novel insights into the differential reprogramming capability between the astrocytes in the grey matter versus the white matter, and highlight the impact of regional astrocytes as well as microenvironment on the outcome of glia-toneuron conversion. Since human brain has large volume of white matter, this study will provide important guidance for future development of in vivo glia-to-neuron conversion technology into potential clinical therapies. Experimental protocols in this study were approved by the Laboratory Animal Ethics Committee of Jinan University(approval No. IACUC-20180321-03) on March 21, 2018. 展开更多
关键词 ASTROCYTE CONVERSION efficiency corpus callosum cortex grey MATTER in vivo cell CONVERSION NeuroD1 neuron REPROGRAMMING STRIATUM white MATTER
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Endothelin increases the proliferation of rat olfactory mucosa cells 预览
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作者 Bertrand Bryche Audrey Saint-Albin +3 位作者 Claire Le Poupon Schlegel Christine Baly Patrice Congar Nicolas Meunier 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期352-360,共9页
The olfactory mucosa holds olfactory sensory neurons directly in contact with an aggressive environment. In order to maintain its integrity, it is one of the few neural zones which are continuously renewed during the ... The olfactory mucosa holds olfactory sensory neurons directly in contact with an aggressive environment. In order to maintain its integrity, it is one of the few neural zones which are continuously renewed during the whole animal life. Among several factors regulating this renewal, endothelin acts as an anti-apoptotic factor in the rat olfactory epithelium. In the present study, we explored whether endothelin could also act as a proliferative factor. Using primary culture of the olfactory mucosa, we found that an early treatment with endothelin increased its growth. Consistently, a treatment with a mixture of BQ123 and BQ788(endothelin receptor antagonists) decreased the primary culture growth without affecting the cellular death level. We then used combined approaches of calcium imaging, reverse transcriptase-quantitative polymerase chain reaction and protein level measurements to show that endothelin was locally synthetized by the primary culture until it reached confluency. Furthermore, in vivo intranasal instillation of endothelin receptor antagonists led to a decrease of olfactory mucosa cell expressing proliferating cell nuclear antigen(PCNA), a marker of proliferation. Only short-term treatment reduced the PCNA level in the olfactory mucosa cells. When the treatment was prolonged, the PCNA level was not statistically affected but the expression level of endothelin was increased. Overall, our results show that endothelin plays a proliferative role in the olfactory mucosa and that its level is dynamically regulated. This study was approved by the Comité d’éthique en expérimentation animale COMETHEA(COMETHEA C2 EA-45;protocol approval #12-058) on November 28, 2012. 展开更多
关键词 AUTOCRINE factor cell CULTURE cellular dynamics ENDOTHELIN OLFACTION OLFACTORY basal CELLS OLFACTORY epithelium OLFACTORY mucosa primary CULTURE
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Unfolded protein response in myelin disorders 预览
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作者 Wensheng Lin Sarrabeth Stone 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期636-645,共10页
Activation of the unfolded protein response in response to endoplasmic reticulum stress preserves cell viability and function under stressful conditions.Nevertheless,persistent,unresolvable activation of the unfolded ... Activation of the unfolded protein response in response to endoplasmic reticulum stress preserves cell viability and function under stressful conditions.Nevertheless,persistent,unresolvable activation of the unfolded protein response can trigger apoptosis to eliminate stressed cells.Recent studies show that the unfolded protein response plays an important role in the pathogenesis of various disorders of myelin,including multiples sclerosis,Charcot-Marie-Tooth disease,Pelizaeus-Merzbacher disease,vanishing white matter disease,spinal cord injury,tuberous sclerosis complex,and hypoxia-induced perinatal white matter injury.In this review we summarize the current literature on the unfolded protein response and the evidence for its role in the pathogenesis of myelin disorders. 展开更多
关键词 AXON ER multiples SCLEROSIS MYELIN OLIGODENDROCYTE Schwann cell spinal cord injury UPR
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Three-dimensional bioprinting collagen/silk fibroin scaffold combined with neural stem cells promotes nerve regeneration after spinal cord injury 预览
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作者 Ji-Peng Jiang Xiao-Yin Liu +9 位作者 Fei Zhao Xiang Zhu Xiao-Yin Li Xue-Gang Niu Zi-Tong Yao Chen Dai Hui-You Xu Ke Ma Xu-Yi Chen Sai Zhang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期959-968,共10页
Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods... Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods for neural regeneration.This study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal cord.This scaffold allows cell growth in vitro and in vivo.To observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord injury.Forty Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed),spinal cord injury (transection injury of T10 spinal cord without any transplantation),3D-CF (3D scaffold was transplanted into the local injured cavity),and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured cavity.Neuroelectrophysiology,imaging,hematoxylin-eosin staining,argentaffin staining,immunofluorescence staining,and western blot assay were performed.Apart from the sham group,neurological scores were significantly higher in the 3D-CF + NSCs group compared with other groups.Moreover,latency of the 3D-CF + NSCs group was significantly reduced,while the amplitude was significantly increased in motor evoked potential tests.The results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs group.Moreover,regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other groups.These results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal cord.This study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No.2017-0007.2). 展开更多
关键词 3D BIOPRINTING COLLAGEN diffusion tensor IMAGING functional recovery magnetic resonance IMAGING nerve REGENERATION NEURAL REGENERATION NEURAL stem cell SCAFFOLD silk fibroin spinal cord injury
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Time course analysis of sensory axon regeneration in vivo by directly tracing regenerating axons 预览
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作者 Yan Gao Yi-Wen Hu +3 位作者 Run-Shan Duan Shu-Guang Yang Feng-Quan Zhou Rui-Ying Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第6期1160-1165,共6页
Most current studies quantify axon regeneration by immunostaining regeneration-associated proteins,representing indirect measurement of axon lengths from both sensory neurons in the dorsal root ganglia and motor neuro... Most current studies quantify axon regeneration by immunostaining regeneration-associated proteins,representing indirect measurement of axon lengths from both sensory neurons in the dorsal root ganglia and motor neurons in the spinal cord.Our recently developed method of in vivo electroporation of plasmid DNA encoding for enhanced green fluorescent protein into adult sensory neurons in the dorsal root ganglia provides a way to directly and specifically measure regenerating sensory axon lengths in whole-mount nerves.A mouse model of sciatic nerve compression was established by squeezing the sciatic nerve with tweezers.Plasmid DNA carrying enhanced green fluorescent protein was transfected by ipsilateral dorsal root ganglion electroporation 2 or 3 days before injury.Fluorescence distribution of dorsal root or sciatic nerve was observed by confocal microscopy.At 12 and 18 hours,and 1,2,3,4,5,and 6 days of injury,lengths of regenerated axons after sciatic nerve compression were measured using green fluorescence images.Apoptosis-related protein caspase-3 expression in dorsal root ganglia was determined by western blot assay.We found that in vivo electroporation did not affect caspase-3 expression in dorsal root ganglia.Dorsal root ganglia and sciatic nerves were successfully removed and subjected to a rapid tissue clearing technique.Neuronal soma in dorsal root ganglia expressing enhanced green fluorescent protein or fluorescent dye-labeled microRNAs were imaged after tissue clearing.The results facilitate direct time course analysis of peripheral nerve axon regeneration.This study was approved by the Institutional Animal Care and Use Committee of Guilin Medical University,China(approval No.GLMC201503010)on March 7,2014. 展开更多
关键词 axon regeneration cell apoptosis dorsal root ganglion in vivo electroporation micro RNAs peripheral nervous system sciatic nerve tissue clearing
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Current status and future prospects of stem cell therapy in Alzheimer’s disease 预览
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作者 Fu-Qiang Zhang Jin-Lan Jiang +3 位作者 Jing-Tian Zhang Han Niu Xue-Qi Fu Lin-Lin Zeng 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期242-250,共9页
Alzheimer’s disease is a common progressive neurodegenerative disorder, pathologically characterized by the presence of β-amyloid plaques and neurofibrillary tangles. Current treatment approaches using drugs only al... Alzheimer’s disease is a common progressive neurodegenerative disorder, pathologically characterized by the presence of β-amyloid plaques and neurofibrillary tangles. Current treatment approaches using drugs only alleviate the symptoms without curing the disease, which is a serious issue and influences the quality of life of the patients and their caregivers. In recent years, stem cell technology has provided new insights into the treatment of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Currently, the main sources of stem cells include neural stem cells, embryonic stem cells, mesenchymal stem cells, and induced pluripotent stem cells. In this review, we discuss the pathophysiology and general treatment of Alzheimer’s disease, and the current state of stem cell transplantation in the treatment of Alzheimer’s disease. We also assess future challenges in the clinical application and drug development of stem cell transplantation as a treatment for Alzheimer’s disease. 展开更多
关键词 Alzheimer's disease β-amyloid drug development embryonic STEM CELLS induced PLURIPOTENT STEM CELLS mesenchymal STEM CELLS nerve REGENERATION NEURAL REGENERATION NEURAL STEM CELLS NEURODEGENERATIVE disorders STEM cell therapy
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Astrocytic modulation of potassium under seizures 预览
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作者 Fushun Wang Xiaoming Qi +1 位作者 Jun Zhang Jason HHuang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第6期980-987,共8页
The contribution of an impaired astrocytic K^+ regulation system to epileptic neuronal hyperexcitability has been increasingly recognized in the last decade.A defective K^+ regulation leads to an elevated extracellula... The contribution of an impaired astrocytic K^+ regulation system to epileptic neuronal hyperexcitability has been increasingly recognized in the last decade.A defective K^+ regulation leads to an elevated extracellular K^+ concentration([K^+]o).When[K^+]o reaches peaks of 10-12 mM,it is strongly associated with seizure initiation during hypersynchronous neuronal activities.On the other hand,reactive astrocytes during a seizure attack restrict influx of K^+ across the membrane both passively and actively.In addition to decreased K^+ buffering,aberrant Ca^2+ signaling and declined glutamate transport have also been observed in astrogliosis in epileptic specimens,precipitating an increased neuronal discharge and induction of seizures.This review aims to provide an overview of experimental findings that implicated astrocytic modulation of extracellular K^+ in the mechanism of epileptogenesis. 展开更多
关键词 AQP4 Ca^2+ signaling cell volume CONNEXINS EPILEPSY K^+ buffering mi RNA NKCC PANNEXIN TBI
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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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Claudin-15 overexpression inhibits proliferation and promotes apoptosis of Schwann cells in vitro 预览
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作者 Jian-Nan Li Zhan Zhang +2 位作者 Guang-Zhi Wu Deng-Bing Yao Shu-Sen Cui 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第1期169-177,共9页
Our previous experiments have discovered that Claudin-15 was up-regulated in Schwann cells of the distal nerve stumps of rat models of sciatic nerve injury.However,how Claudin-15 affects Schwann cell function is still... Our previous experiments have discovered that Claudin-15 was up-regulated in Schwann cells of the distal nerve stumps of rat models of sciatic nerve injury.However,how Claudin-15 affects Schwann cell function is still unknown.This study aimed to identify the effects of Claudin-15 on proliferation and apoptosis of Schwann cells cultured in vitro and explore the underlying mechanisms.Primary Schwann cells were obtained from rats.Claudin-15 in Schwann cells was knocked down using siRNA(siRNA-1 group)compared with the negative control siRNA transfection group(negative control group).Claudin-15 in Schwann cells was overexpressed using pGV230-Claudin-15 plasmid(pGV230-Claudin-15 group).The pGV230 transfection group(pGV230 group)acted as the control of the pGV230-Claudin-15 group.Cell proliferation was analyzed with EdU assay.Cell apoptosis was analyzed with flow cytometric analysis.Cell migration was analyzed with Transwell inserts.The mRNA and protein expressions were analyzed with quantitative polymerase chain reaction assay and western blot assay.The results showed that compared with the negative control group,cell proliferation rate was up-regulated;p-AKT/AKT ratio,apoptotic rate,p-c-Jun/c-Jun ratio,mRNA expression of protein kinase C alpha,Bcl-2 and Bax were down-regulated;and mRNA expression of neurotrophins basic fibroblast growth factor and neurotrophin-3 were increased in the siRNA-1 group.No significant difference was found in cell migration between the negative control and siRNA-1 groups.Compared with the pGV230 group,the cell proliferation rate was down-regulated;apoptotic rate,p-c-Jun/c-Jun ratio and c-Fos protein expression increased;mRNA expression of protein kinase C alpha and Bax decreased;and mRNA expressions of neurotrophins basic fibroblast growth factor and neurotrophin-3 were up-regulated in the pGV230-Claudin-15 group.The above results demonstrated that overexpression of Claudin-15 inhibited Schwann cell proliferation and promoted Schwann cell apoptosis in vitro.Silencing of Claudin-15 had the re 展开更多
关键词 apoptosis Bax cell PROLIFERATION c-Jun Claudin-15 NERVE regeneration peripheral NERVE injury protein kinase C alpha Schwann cells Wallerian DEGENERATION
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Bone marrow-derived mesenchymal stem cell transplantation attenuates overexpression of inflammatory mediators in rat brain after cardiopulmonary resuscitation 预览
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作者 Qing-Ming Lin Xia-Hong Tang +2 位作者 Shi-Rong Lin Ben-Dun Chen Feng Chen 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期324-331,共8页
Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain un... Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline(control) or 1 × 10~6 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100 B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100 B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, macrophage inflammatory protein-3α, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ≥ 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ≥ 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and 展开更多
关键词 antibody array ASPHYXIA brain damage cardiac arrest CARDIOPULMONARY RESUSCITATION global cerebral ischemia inflammatory mediator mesenchymal stem cell NEUROLOGICAL DEFICIT score S100B
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A mimetic peptide ofα2,6-sialyllactose promotes neuritogenesis 预览
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作者 Shuang-Xi Chen Jia-Hui He +3 位作者 Yong-Jian Mi Hui-Fan Shen Melitta Schachner Wei-Jiang Zhao 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第6期1058-1065,共8页
Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(... Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(6'-SL),which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6'-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin.Indeed,lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6'-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H_20_2-induced oxidative stress.The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China(approval No.SUMC 2014-004)on February 20,2014. 展开更多
关键词 central nervous system cerebellar granule neurons mimetic peptide neural cell adhesion molecule L1 NEURITOGENESIS neurodegenerative disease neuronal survival oxidative stress phage display Sambucus nigra lectin α2 6-sialyllactose
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Therapeutic potential of natural compounds from Chinese medicine in acute and subacute phases of ischemic stroke 预览
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作者 Bei Zhang Kathryn ESaatman Lei Chen 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第3期416-424,共9页
Stroke is one of the leading causes of death and disability in adults worldwide,resulting in huge social and financial burdens.Extracts from herbs,especially those used in Chinese medicine,have emerged as new pharmace... Stroke is one of the leading causes of death and disability in adults worldwide,resulting in huge social and financial burdens.Extracts from herbs,especially those used in Chinese medicine,have emerged as new pharmaceuticals for stroke treatment.Here we review the evidence from preclinical studies investigating neuroprotective properties of Chinese medicinal compounds through their application in acute and subacute phases of ischemic stroke,and highlight potential mechanisms underlying their therapeutic effects.It is noteworthy that many herbal compounds have been shown to target multiple mechanisms and in combinations may exert synergistic effects on signaling pathways,thereby attenuating multiple aspects of ischemic pathology.We conclude the paper with a general discussion of the prospects for novel natural compound-based regimens against stroke. 展开更多
关键词 cell death HERBAL compound immune response ISCHEMIC stroke therapy NEUROPLASTICITY NEUROPROTECTION oxidative damage traditional Chinese medicine
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Korean red ginseng promotes hippocampal neurogenesis in mice 预览
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作者 Sun Ryu Hyongjun Jeon +2 位作者 Hee-Young Kim Sungtae Koo Seungtae Kim 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期887-893,共7页
Neurogenesis in the adult hippocampus plays a major role in cognitive ability of animals including learning and memory.Korean red ginseng (KRG) has long been known as a medicinal herb with the potential to improve lea... Neurogenesis in the adult hippocampus plays a major role in cognitive ability of animals including learning and memory.Korean red ginseng (KRG) has long been known as a medicinal herb with the potential to improve learning and memory;however,the mechanisms are still elusive.Therefore,we evaluated whether KRG can promote cognitive function and enhance neurogenesis in the hippocampus.Eight-week-old male C57BL/6 mice received 50 mg/kg of 5-bromo-2′-deoxyuridine (BrdU) intraperitoneally and 100 mg/kg of KRG or vehicle orally once a day for 14 days.Pole,Rotarod and Morris water maze tests were performed and the brains were collected after the last behavioral test.Changes in the numbers of BrdU- and BrdU/ doublecortin (DCX;a marker for neuronal precursor cells and immature neurons)-positive cells in the dentate gyrus and the gene expression of proliferating cell nuclear antigen (a marker for cell differentiation),cerebral dopamine neurotrophic factor and ciliary neurotrophic factor in the hippocampus were then investigated.KRG-treated mice came down the pole significantly faster and stood on the rotarod longer than vehicle-treated mice.The Morris water maze test showed that KRG administration enhanced the learning and memory abilities significantly.KRG also significantly increased BrdU- and BrdU/DCX-positive cells in the dentate gyrus as well as the proliferating cell nuclear antigen,cerebral dopamine neurotrophic factor and ciliary neurotrophic factor mRNA expression levels in the hippocampus compared to vehicle.Administration of KRG promotes learning and memory abilities,possibly by enhancing hippocampal neurogenesis.This study was approved by the Pusan National University Institutional Animal Care and Use Committee (approval No.PNU-2016-1071) on January 19,2016. 展开更多
关键词 BROMODEOXYURIDINE cerebral dopamine NEUROTROPHIC FACTOR ciliary NEUROTROPHIC FACTOR DOUBLECORTIN GINSENG hippocampus Korean RED GINSENG learning memory neurogenesis proliferating cell nuclear antigen RED GINSENG
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