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Baculoviral inhibitor of apoptosis protein repeatcontaining protein 3 delays early wallerian degeneration after sciatic nerve injury

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Neural Regeneration Research 2022年第4期17卷 845-853页

作者： Min Cai Jian Shao Bryant Yung Yi Wang Nan-Nan Gao Xi Xu Huan-Huan Zhang Yu-Mei Feng Deng-Bing Yao Nantong University Medical School NantongJiangsu ProvinceChina School of Life Sciences Jiangsu Key Laboratory of NeuroregenerationCo-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Department of Hand Surgery China-Japan Union Hospital of Jilin UniversityChangchunJilin ProvinceChina

wallerian degeneration is a complex biological process that occurs after nerve injury,and involves nerve degeneration and *** cells play a crucial role in the cellular and molecular events of wallerian degeneration of the peripheral nervous ***,wallerian degeneration regulating nerve injury and repair remains largely unknown,especially the early *** have previously reported some key regulators of wallerian degeneration after sciatic nerve *** inhibitor of apoptosis protein repeat-containing protein 3(BIRC3)is an important factor that regulates apoptosis-inhibiting *** this study,we established rat models of right sciatic nerve *** vitro Schwann cell models were also established and subjected to gene transfection to inhibit and overexpress *** data indicated that BIRC3 expression was significantly up-regulated after sciatic nerve *** BIRC3 upregulation and downregulation affected the migration,proliferation and apoptosis of Schwan cells and affected the expression of related factors through activating c-fos and ERK signal *** of BIRC3 delayed early wallerian degeneration through inhibiting the apoptosis of Schwann cells after sciatic nerve *** findings suggest that BIRC3 plays an important role in peripheral nerve injury repair and *** study was approved by the Institutional Animal Care and Use Committee of Nantong University,China(approval No.2019-nsfc004)on March 1,2019.

关键词： apoptosis baculoviral inhibitor of apoptosis protein repeat-containing protein 3 nerve degeneration rat Schwann cell sciatic nerve injury signal pathway wallerian degeneration

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Visualizing wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

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Neural Regeneration Research 2024年第3期19卷 636-641页

作者： Jiao Mu Liufang Hao Zijue Wang Xuyang Fu Yusen Li Fei Hao Hongmei Duan Zhaoyang Yang Xiaoguang Li Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stroke can cause wallerian degeneration in regions outside of the brain,particularly in the corticospinal *** investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke,we induced photochemical infarction of the sensorimotor cortex leading to wallerian degeneration along the full extent of the corticospinal *** first used a routine,sensitive marker of axonal injury,amyloid precursor protein,to examine wallerian degeneration of the corticospinal *** antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex,with no positive signal in distal parts of the corticospinal tract,at all time *** improve visualization of wallerian degeneration,we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing *** this approach,we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after *** addition,microglia mobilized and activated early,from day 7 after stroke,but did not maintain a phagocytic state over ***,astrocytes showed relatively delayed mobilization and a moderate response to wallerian ***,no anterograde degeneration of spinal anterior horn cells was observed in response to wallerian degeneration of the corticospinal *** conclusion,our data provide evidence for dynamic,pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during wallerian degeneration.

关键词： corticospinal tract green fluorescent protein microglia spinal anterior horn cells stroke virus trace wallerian degeneration

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Neutrophil peptide 1 accelerates the clearance of degenerative axons during wallerian degeneration by activating macrophages after peripheral nerve crush injury

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Neural Regeneration Research 2024年第8期19卷 1822-1827页

作者： Yuhui Kou Yusong Yuan Qicheng Li Wenyong Xie Hailin Xu Na Han Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina National Center for Trauma Medicine BeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Department of Orthopedics China-Japan Friendship HospitalBeijingChina Department of Central Laboratory and Institute of Clinical Molecular Biology Peking University People’s HospitalBeijingChina

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still *** preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve ***,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains *** study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush *** functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent *** debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during wallerian *** inflammatory factor expression in different polarization states was detected using a protein *** results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 *** axonal debris clearance rate during wallerian degeneration was enhanced after neutrophil peptide 1 *** peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in ***,the results suggest that neutrophil peptide 1 activates macrophages and accelerates wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

关键词： axonal debris inflammatory factors macrophages neutrophil peptide 1 peripheral nerve injury peripheral nerve regeneration RAW 264.7 cells sciatic nerve wallerian degeneration

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Identification of key genes involved in axon regeneration and wallerian degeneration by weighted gene co-expression network analysis

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Neural Regeneration Research 2022年第4期17卷 911-919页

作者： Yan Lu Qi Shan Mei Ling Xi-An Ni Su-Su Mao Bin Yu Qian-Qian Cao Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina School of Life Sciences Nantong UniversityNantongJiangsu ProvinceChina

Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and wallerian ***,investigating how axon regeneration and degeneration work together to repair peripheral nerve injury may uncover the molecular mechanisms and signal cascades underlying peripheral nerve repair and provide potential strategies for improving the low axon regeneration capacity of the central nervous *** this study,we applied weighted gene co-expression network analysis to identify differentially expressed genes in proximal and distal sciatic nerve segments from rats with sciatic nerve *** identified 31 and 15 co-expression modules from the proximal and distal sciatic nerve segments,*** enrichment analysis revealed that the differentially expressed genes in proximal modules promoted regeneration,while the differentially expressed genes in distal modules promoted ***,we constructed hub gene networks for selected modules and identified a key hub gene,Kif22,which was up-regulated in both nerve *** vitro experiments confirmed that Kif22 knockdown inhibited proliferation and migration of Schwann cells by modulating the activity of the extracellular signal-regulated kinase signaling ***,our findings provide a comparative framework of gene modules that are co-expressed in injured proximal and distal sciatic nerve segments,and identify Kif22 as a potential therapeutic target for promoting peripheral nerve injury repair via Schwann cell proliferation and *** animal experiments were approved by the Institutional Animal Ethics Committee of Nantong University,China(approval No.S20210322-008)on March 22,2021.

关键词： axon regeneration extracellular signal-regulated kinase signaling pathway hub genes Kif22 peripheral nerve injury protein kinase Cα Schwann cells wallerian degeneration weighted gene co-expression network analysis

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Combining CUBIC Optical Clearing and Thy1-YFP-16 Mice to Observe Morphological Axon Changes During wallerian degeneration

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Current Medical Science 2021年第5期41卷 944-952页

作者： Yu-song YUAN Fei YU Su-ping NIU Hao LU Yu-hui KOU Hai-lin XU Department of Trauma and Orthopaedics Peking University People's HospitalPeking University'Beijing 100044China National and Local Joint Engineering Research Center of Orthopaedic Biomaterials Department of Bone&Joint SurgeryPeking University Shenzhen HospitalShenzhen 518036China Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijing 100044China Office of Academic Research Peking University People's HospitalPeking UniversityBeijing 100044China Diabetic Foot Treatment Center Peking University People's HospitalPeking University'Beijing 100044China

Objective:wallerian degeneration is a pathological process closely related to peripheral nerve regeneration following injury,and includes the disintegration and phagocytosis of peripheral nervous system ***,morphological changes are observed by performing immunofluorescence staining after sectioning,which results in the loss of some histological *** purpose of this study was to explore a new,nondestmetive,and systematic method for observing axonal histological changes during wallerian ***:Thirty male Thy1-YFP-16 mice(SPF grade,6 weeks old,20±5 g)were randomly selected and divided into clear,unobstructed brain imaging cocktails and computational analysis(CUBIC)optical clearing(n=15)and traditional method groups(n=15).Five mice in each group were sacrificed at 1st,3rd,and 5th day following a crush *** histological axon changes were observed by CUBIC light optical clearing treatment,direct tissue section imaging,and HE ***:The results revealed that,compared with traditional imaging methods,there was no physical damage to the samples,which allowed for three-dimensional and deep-seated tissue imaging through *** image information could be nicely obtained by direct fluorescence imaging and HE staining,but it was difficult to obtain image information of the entire *** the same time,the image information obtained by fluorescence imaging and HE staining was partially ***:The combining of CUBIC and Thy1-YFP transgenic mice allowed for a clear and comprehensive observation of histological changes of axons in wallerian degeneration.

关键词： wallerian degeneration axon optical clearing clear,unobstructed brain imaging cocktails and computational analysis Thy1-YFP transgenic mice

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Diffusion tensor imaging detects wallerian degeneration of the corticospinal tract early after cerebral infarction

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Neural Regeneration Research 2012年第12期7卷 900-905页

作者： Ruiman Xie Min Fang Linjiang Zhou Shanghua Fan Jianying Liu Hongbo Quan Man Luo Dongying Qiu Department of Neurology and Gerontology Zhongshan Hospital Fudan University Shanghai 200032 China Department of Radiology Huashan Hospital Fudan University Shanghai 200040 China

To investigate the feasibility and time window of early detection of wallerian degeneration in the corticospinal tract after middle cerebral artery infarction, 23 patients were assessed using magnetic resonance diffusion tensor imaging at 3.0T within 14 days after the infarction. The fractional anisotropy values of the affected corticospinal tract began to decrease at 3 days after onset and decreased in all cases at 7 days. The diffusion coefficient remained unchanged. Experimental findings indicate that diffusion tensor imaging can detect the changes associated with wallerian degeneration of the corticospinal tract as early as 3 days after cerebral infarction.

关键词： corticospinal tracts wallerian degeneration fractional anisotropy diffusion tensor imaging neuroimaging neural regeneration

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Expression changes and bioinformatic analysis of wallerian degeneration after sciatic nerve injury in rat

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Neuroscience Bulletin 2013年第3期29卷 321-332页

作者： Dengbing Yao Meiyuan Li Dingding Shen Fei Ding Shibi Lu Qing Zhao Xiaosong Gu Jiangsu Key Laboratory of Neuroregeneration Nantong University School of Life Sciences Nantong University Key Laboratory of the People's Liberation Army Institute of Orthopaedics Chinese PLA General Hospital

wallerian degeneration （WD） remains an important research topic. Many genes are differentially expressed during the process of WD, but the precise mechanisms responsible for these differentiations are not completely understood. In this study, we used microarrays to analyze the expression changes of the distal nerve stump at 0, 1, 4, 7, 14, 21 and 28 days after sciatic nerve injury in rats. The data revealed 6 076 differentiatly-expressed genes, with 23 types of expression, specifically enriched in genes associated with nerve development and axonogenesis, cytokine biosynthesis, cell differentiation, cytokine/chemokine production, neuron differentiation, cytokinesis, phosphorylation and axon regeneration. Kyoto Encyclopedia of Genes and Genomes pathway analysis gave findings related mainly to the MAPK signaling pathway, the Jak-STAT signaling pathway, the cell cycle, cytokine-cytokine receptor interaction, the p53 signaling pathway and the Wnt signaling pathway. Some key factors were NGF, MAG, CNTF, CTNNA2, p53, JAK2, PLCB1, STAT3, BDNF, PRKC, collagen II, FGF, THBS4, TNC and c-Src, which were further validated by real-time quantitative PCR, Western blot, and immunohistochemistry. Our findings contribute to a better understanding of the functional analysis of differentially-expressed genes in WD and may shed light on the molecular mechanisms of nerve degeneration and regeneration.

关键词： wallerian degeneration rat sciatic nerve expression change microarrays

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Differential gene expression in proximal and distal nerve segments of rats with sciatic nerve injury during wallerian degeneration

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Neural Regeneration Research 2014年第12期9卷 1186-1194页

作者： Nan Jiang Huaiqin Li Yi Sun Dexin Yin Qin Zhao Shusen Cui Dengbing Yao Jiangsu Key Laboratory of Neuroregeneration Nantong University China-Japan Union Hospital of Jilin University Key Laboratory of People’s Liberation Army Institute of Orthopedics Chinese PLA General Hospital

wallerian degeneration is a subject of major interest in neuroscience. A large number of genes are differentially regulated during the distinct stages of wallerian degeneration： transcription factor activation, immune response, myelin cell differentiation and dedifferentiation. Although gene expression responses in the distal segment of the sciatic nerve after peripheral nerve injury are known, differences in gene expression between the proximal and distal segments remain unclear. In the present study in rats, we used microarrays to analyze changes in gene expression, biological processes and signaling pathways in the proximal and distal segments of sciatic nerves under- going wallerian degeneration. More than 6,000 genes were differentially expressed and 20 types of expression tendencies were identified, mainly between proximal and distal segments at 7-14 days after injury. The differentially expressed genes were those involved in cell differentiation, cytokinesis, neuron differentiation, nerve development and axon regeneration. Furthermore, 11 biological processes were represented, related to responses to stimuli, cell apoptosis, inflammato- ry response, immune response, signal transduction, protein kinase activity, and cell proliferation. Using real-time quantitative PCR, western blot analysis and immunohistochemistry, microarray data were verified for four genes： aquaporin-4, interleukin 1 receptor-like 1, matrix metallopro- teinase-12 and periaxin. Our study identifies differential gene expression in the proximal and distal segments of a nerve during wallerian degeneration, analyzes dynamic biological changes of these genes, and provides a useful platform for the detailed study of nerve injury and repair during wallerian degeneration.

关键词： nerve regeneration peripheral nerve injury wallerian degeneration sciatic nerve injury microarray expression profiling biological process rat NSFC grant neural regeneration

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Gene expression profiling of the rat sciatic nerve in early wallerian degeneration after injury

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Neural Regeneration Research 2012年第17期7卷 1285-1292页

作者： Dengbing Yao Meiyuan Li Dingding Shen Fei Ding Shibi Lu Qin Zhao Xiaosong Gu Jiangsu Key Laboratory of Neuroregeneration Nantong University Nantong 226019 Jiangsu Province China School of Life Sciences Nantong University Nantong 226019 Jiangsu Province China Key Laboratory of People＇s Liberation Army Institute of Orthopedics Chinese PLA General Hospital Beijing 100853 China

wallerian degeneration is an important area of research in modern neuroscience. A large number of genes are differentially regulated in the various stages of wallerian degeneration, especially during the early response. In this study, we analyzed gene expression in early wallerian degeneration of the distal nerve stump at 0, 0.5, 1,6, 12 and 24 hours after rat sciatic nerve injury using gene chip microarrays. We screened for differentially-expressed genes and gene expression patterns. We examined the data for Gene Ontology, and explored the Kyoto EncycLopedia of Genes and Genomes Pathway. This allowed us to identify key regulatory factors and recurrent network motifs. We identified 1 546 differentially-expressed genes and 21 distinct patterns ofgene expression in early wallerian degeneration, and an enrichment of genes associated with the immune response, acute inflammation, apoptosis, cell adhesion, ion transport and the extracellular matrix. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed components involved in the Jak-STAT, ErbB, transforming growth factor-13, T cell receptor and calcium signaling pathways. Key factors included interleukin-6, interleukin-1, integrin, c-sarcoma, carcinoembryonic antigen-related cell adhesion molecules, chemokine （C-C motif） ligand, matrix metalloproteinase, BH3 interacting domain death agonist, baculoviral lAP repeat-containing 3 and Rac. The data were validated with real-time quantitative PCR. This study provides a global view of gene expression profiles in eady wallerian degeneration of the rat sciatic nerve. Our findings provide insight into the molecular mechanisms underlying early wallerian degeneration, and the regulation of nerve degeneration and regeneration.

关键词： wallerian degeneration sciatic nerve microarrays expression profiling rats neural regeneration

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The effects of claudin 14 during early wallerian degeneration after sciatic nerve injury

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Neural Regeneration Research 2014年第24期9卷 2151-2158页

作者： Leilei Gong Yun Zhu Xi Xu Huaiqin Li Weimin Guo Qin Zhao Dengbing Yao Jiangsu Key Laboratory of Neuroregeneration Co-innovation Center of Neuroregeneration Key Laboratory of People’s Liberation Army Institute of Orthopedics Chinese PLA General Hospital School of Life Sciences Nantong University

Claudin 14 has been shown to promote nerve repair and regeneration in the early stages of wallerian degeneration （0-4 days） in rats with sciatic nerve injury, but the mechanism underlying this process remains poorly understood. This study reported the effects of claudin 14 on nerve degeneration and regeneration during early wallerian degeneration. Claudin 14 expression was up-regulated in sciatic nerve 4 days after wallerian degeneration. The altered expression of claudin 14 in Schwann cells resulted in expression changes of cytokines in vitro. Expression of claudin 14 affected c-Jun, but not Akt anal ERK1/2 patl^ways, l^urther studies reve^ed that enhanced expression of claudin 14 could promote Schwann cell proliferation and migration. Silencing of claudin 14 expression resulted in Schwann cell apoptosis and reduction in Schwann cell proliferation. Our data revealed the role of claudin 14 in early wallerian degeneration, which may provide new insights into the molecular mechanisms of wallerian degeneration.

关键词： nerve regeneration peripheral nerve injury wallerian degeneration sciatic nerve injury Claudin 14 rat Schwann cell Signal pathways c-Jun Akt ERK1/2 NSFC grant neural regeneration

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