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Platelet-rich plasma promotes peripheral nerve regeneration after sciatic nerve injury

Neural Regeneration Research 2023年第2期18卷 375-381页

作者： Su-Long Wang Xi-Lin Liu Zhi-Chen Kang Yue-Shu Wang Department of Hand Surgery China-Japan Union Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Rehabilitation The Second Hospital of Jilin UniversityChangchunJilin ProvinceChina

The effect of platelet-rich plasma on nerve regeneration remains controversial.In this study,we established a rabbit model of sciatic nerve small-gap defects with preserved epineurium and then filled the gaps with platelet-rich plasma.Twenty-eight rabbits were divided into the following groups(7 rabbits/group):model,low-concentrati on PRP(2.5-3.5-fold concentration of whole blood platelets),medium-concentration PRP(4.5-6.5-fold concentration of whole blood platelets),and high-concentration PRP(7.5-8.5-fold concentration of whole blood platelets).Electrophysiological and histomorphometrical assessments and proteomics analysis we re used to evaluate regeneration of the sciatic nerve.Our results showed that platelet-rich plasma containing 4.5-6.5-and 7.5-8.5-fold concentrations of whole blood platelets promoted repair of sciatic nerve injury.Proteomics analysis was performed to investigate the possible mechanism by which platelet-rich plasma promoted nerve regeneration.Proteomics analysis showed that after sciatic nerve injury,platelet-rich plasma increased the expression of integrin subunitβ-8(ITGB8),which participates in angiogenesis,and differentially expressed proteins were mainly enriched in focal adhesion pathways.Additionally,two key proteins,ribosomal protein S27 a(RSP27 a)and ubiquilin 1(UBQLN1),which were selected after protein-protein interaction analysis,are involved in the regulation of ubiquitin levels in vivo.These data suggest that platelet-rich plasma promotes peripheral nerve regeneration after sciatic nerve injury by affecting angiogenesis and intracellular ubiquitin levels.

关键词： bioinformatic analysis ITGB8 leukocyte-platelet rich plasma nerve regeneration peripheral nerve injury platelet-rich plasma proteomic analysis sciatic nerve injury

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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 regeneration.Schwann cells play a crucial role in the cellular and molecular events of Wallerian degeneration of the peripheral nervous system.However,Wallerian degeneration regulating nerve injury and repair remains largely unknown,especially the early response.We have previously reported some key regulators of Wallerian degeneration after sciatic nerve injury.Baculoviral inhibitor of apoptosis protein repeat-containing protein 3(BIRC3)is an important factor that regulates apoptosis-inhibiting protein.In this study,we established rat models of right sciatic nerve injury.In vitro Schwann cell models were also established and subjected to gene transfection to inhibit and overexpress BIRC3.The data indicated that BIRC3 expression was significantly up-regulated after sciatic nerve injury.Both 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 pathway.Inhibition of BIRC3 delayed early Wallerian degeneration through inhibiting the apoptosis of Schwann cells after sciatic nerve injury.These findings suggest that BIRC3 plays an important role in peripheral nerve injury repair and regeneration.The 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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Local vibration therapy promotes the recovery of nerve function in rats with sciatic nerve injury

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Journal of Integrative Medicine 2022年第3期20卷 265-273页

作者： Lu Yin Yun An Xiao Chen Hui-xin Yan Tao Zhang Xin-gang Lu Jun-tao Yan Department of Rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China Department of Tuina Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China Department of Rehabilitation Medicine The Second Rehabilitation Hospital of ShanghaiShanghai 200441China Shanghai Key Laboratory of Clinical Geriatric Medicine Huadong HospitalFudan UniversityShanghai 200040China

Objective:It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury,but the optimized parameters and effective mechanism were unclear.In the present study,we investigated the effect of local vibration therapy of different amplitudes on the recovery of nerve function in rats with sciatic nerve injury(SNI).Methods:Adult male Sprague-Dawley rats were subjected to SNI and then randomly divided into 5 groups:sham group,SNI group,SNI+A-1 mm group,SNI+A-2 mm group,and SNI+A-4 mm group(A refers to the amplitude;n=10 per group).Starting on the 7th day after model initiation,local vibration therapy was given for 21 consecutive days with a frequency of 10 Hz and an amplitude of 1,2 or 4 mm for 5 min.The sciatic function index(SFI)was assessed before surgery and on the 7th,14th,21st and 28th days after surgery.Tissues were harvested on the 28th day after surgery for morphological,immunofluorescence and Western blot analysis.Results:Compared with the SNI group,on the 28th day after surgery,the SFIs of the treatment groups were increased;the difference in the SNI+A-2 mm group was the most obvious(95%confidence interval[CI]:[5.86,27.09],Pnerve growth factor proteins in the treatment groups were increased;the phosphorylation expressions of ERK1/2 protein in the SNI+A-2 mm group and SNI+A-4 mm group were upregulated(95%CI:[0.03,0.96],P=0.038;95%CI:[0.01,0.94],P=0.047,respectively),and the phosphorylation expression of Akt in the SNI+A-1 mm group was upregulated(95%CI:[0.11,2.07],P=0.031).Conclusion:Local vibration therapy,especially with medium amplitude,was able to promote the recovery of nerve function in rats with SNI;this result was linked to the proliferation of Schwann cells and the activation of the ERK1/2 an

关键词： sciatic nerve injury Local vibration therapy nerve function Myelination

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Comparison of the nerve Regeneration Capacity and Characteristics between sciatic nerve Crush and Transection injury Models in Rats

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Biomedical and Environmental Sciences 2023年第2期36卷 160-173页

作者： WANG Bin Bin GUO Chao SUN Sheng Qiao ZHANG Xing Nan LI Zhen LI Wei Jie LI De Zhi SCHUMACHER Michael LIU Song Beijing Neurosurgical Institute Capital Medical UniversityBeijing 100070China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China U1195 Inserm et Universite Paris-SaclayLe Kremlin-Bicetre 94276France

Objective To provide useful information for selecting the most appropriate peripheral nerve injury model for different research purposes in nerve injury and repair studies,and to compare nerve regeneration capacity and characteristics between them.Methods Sixty adult SD rats were randomly divided into two groups and underwent crush injury alone(group A,n=30)or transection injury followed by surgical repair(group B,n=30)of the right hind paw.Each group was subjected to the CatWalk test,gastrocnemius muscle evaluation,pain threshold measurement,electrophysiological examination,retrograde neuronal labeling,and quantification of nerve regeneration before and 7,14,21,and 28 days after injury.Results Gait analysis showed that the recovery speed in group A was significantly faster than that in group B at 14 days.At 21 days,the compound muscle action potential of the gastrocnemius muscle in group A was significantly higher than that in group B,and the number of labeled motor neurons in group B was lower than that in group A.The number of new myelin sheaths and the g-ratio were higher in group A than in group B.There was a 7-day time difference in the regeneration rate between the two injury groups.Conclusion The regeneration of nerve fibers was rapid after crush nerve injury,whereas the transection injury was relatively slow,which provides some ideas for the selection of clinical research models.

关键词： sciatic nerve injury Degeneration Regeneration Myelination

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Label-free quantitative proteomics analysis models in vivo and in vitro reveal key proteins and potential roles in sciatic nerve injury

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生物细胞(英文) 2023年第9期47卷 2069-2080页

作者： YANG GU MINGGUANG BI DEHUI CHEN NING NI JIANMING CHEN Department of Trauma Orthopedics Surgery Ningbo No.6 HospitalNingbo University School of MedicineNingbo315000China Department of Orthopedics Ningbo Medical CenterLihuili HospitalNingbo University School of MedicineNingbo315000China Department of Orthopedic Surgery Fujian Medical University Union HospitalFuzhou350001China School of Medicine Ningbo UniversityNingbo315000China

Background:The underlying mechanism of sciatic nerve injury(SNI)is a common motor functional disorder,necessitates further research.Methods:A rat model of SNI was established,with the injury group subjected to compressive injury of the right sciatic nerve exposed at the midpoint of the thigh and the sham surgery group undergoing the same surgical procedure.An oxygen-glucose deprivation model was employed to simulate in vitro SNI in PC12 cells.Following data acquisition and quality control,differentially expressed proteins(DEPs)in each model were identified through differential analysis,and enrichment analysis was used to explore the potential functions and pathways of the DEPs.Venn diagrams were drawn,and DEPs from both in vivo and in vitro SNI models were imported into the STRING database to construct a protein-protein interaction network and screen for hub proteins.Results:After the peptide segments obtained from rat nerve blockade and PC12 cells met quality requirements,258 DEPs were identified in rat nerve samples,and 119 DEPs were screened in PC12 cells.Enrichment analysis revealed that DEPs in the rat model were predominantly concentrated in biological functions such as myogenic cell proliferation and signaling related to lipid and energy metabolism.DEPs in the in vitro model were mainly enriched in biological processes such as phagocytosis and were associated with lipid transport and metabolism.Two hub proteins,amyloid precursor protein(APP)and fibronectin 1(FN1),were identified through MCC,MCODE,and Degree scoring.Both PC12 cells and external validation sets showed relatively higher expression of APP and FN1 in injured samples.Results of gene set enrichment analysis indicated that these two proteins were associated with metabolic pathways,such as biosynthesis of glycosaminoglycan chondroitin sulfate and biosynthesis of unsaturated fatty acids.Conclusion:APP and FN1 are potential key molecules involved in SNI and are associated with various metabolic pathways in nerve repair.These findings provide a theore

关键词： Oxygen glucose deprivation Proteomics sciatic nerve injury Peripheral nerve injury

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sciatic nerve injury repair: a visualized analysis of research fronts and development trends

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Neural Regeneration Research 2014年第18期9卷 1716-1722页

作者： Guangyao Liu Rui Jiang Yan Jin Department of Orthopedics China-Japan Union HospitalJilin University Department of Ophthalmology Second Hospital of Jilin University

A total of 3,446 publications regarding sciatic nerve injury repair and protection indexed by Web of Science during 2000-2004 were used for a detailed analysis of temporal-spatial distribu- tion characteristics. Reference co-citation networks of the 100 top-cited publications as per the number of total citations were created using the Web of Science database and the information visualization tool, CiteSpaceIIL The key words that showed high frequency in these publications were included for analyzing the research fronts and development trends for sciatic nerve injury repair and protection. Through word frequency trend analysis, studies on bone marrow mesen- chymal stem cells, adipose-derived stem cells, and skeletal muscle-derived multipotent stem cells combined with tissue-engineered scaffold material will become the forefronts in the field of sci- atic nerve injury repair and protection in the near future.

关键词： nerve regeneration sciatic nerve injury nerve repair neuroprotection referenceco-citation networks Web of Science CiteSpace neural regeneration

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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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Saikosaponin a increases interleukin-10 expression and inhibits scar formation after sciatic nerve injury

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Neural Regeneration Research 2018年第9期13卷 1650-1656页

作者： Meng-Qiang Huang Xiao-Yu Cao Xu-Yi Chen Ying-Fu Liu Shuang-Long Zhu Zhong-Lei Sun Xian-Bin Kong Jing-Rui Huo Sai Zhang Yun-Qiang Xu Graduate School Tianjin Medical University Department of Orthopedics Tianjin Medical University General Hospital Department of Rehabilitation Medicine First Affiliated Hospital of Anhui Medical University Tianjin Key Laboratory of Neurotrauma Repair Institute of Traumatic Brain Injury and NeuroscienceCenter for Neurology and Neurosurgery of Affiliated HospitalLogistics University of Chinese People's Armed Police Force Science and Technology Experiment Center Cangzhou Medical College Graduate School Jinzhou Medical University Graduate School Tianjin University of Traditional Chinese Medicine

nerve scarring after peripheral nerve injury can severely hamper nerve regeneration and functional recovery.Further,the anti-inflammatory cytokine,interleukin-10,can inhibit nerve scar formation.Saikosaponin a（SSa） is a monomer molecule extracted from the Chinese medicine,Bupleurum.SSa can exert anti-inflammatory effects in spinal cord injury and traumatic brain injury.However,it has not been shown whether SSa can play a role in peripheral nerve injury.In this study,rats were randomly assigned to three groups.In the sham group,the left sciatic nerve was directly sutured after exposure.In the sciatic nerve injury（SNI）＋ SSa and SNI groups,the left sciatic nerve was sutured and continuously injected daily with SSa（10 mg/kg） or an equivalent volume of saline for 7 days.Enzyme linked immunosorbent assay results demonstrated that at 7 days after injury,interleukin-10 level was considerably higher in the SNI ＋ SSa group than in the SNI group.Masson staining and western blot assay demonstrated that at 8 weeks after injury,type I and III collagen content was lower and nerve scar formation was visibly less in the SNI ＋ SSa group compared with the SNI group.Simultaneously,sciatic functional index and nerve conduction velocity were improved in the SNI ＋ SSa group compared with the SNI group.These results confirm that SSa can increase the expression of the anti-inflammatory factor,interleukin-10,and reduce nerve scar formation to promote functional recovery of injured sciatic nerve.

关键词： nerve regeneration saikosaponin a anti-inflammatory factor inflammation interleukin-l O nerve scar peripheral nerve injury sciatic nerve injury sciatic functional index nerve conduction velocity neuroelectrophysiological function neural regeneration

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Differential expression of microRNAs in dorsal root ganglia after sciatic nerve injury

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Neural Regeneration Research 2014年第10期9卷 1031-1040页

作者： Anjie Lu Zufa Huang Chaoyue Zhang Xianfang Zhang Jiuhong Zhao Haiying Zhang Quanpeng Zhang Song Wu Xinan Yi Department of Orthopedics the Third Xiangya HospitalCentral South University Neurosciences Research Department Hainan Medical University

This study investigated the possible involvement of microRNAs in the regulation of genes that participate in peripheral neural regeneration. A microRNA microarray analysis was conducted and 23 microRNAs were identiifed whose expression was signiifcantly changed in rat dorsal root ganglia after sciatic nerve transection. The expression of one of the downregulated microRNAs, microRNA-214, was validated using quantitative reverse transcriptase-PCR. MicroRNA-214 was predicted to target the 3′-untranslated region of Slit-Robo GTPase-activating protein 3. In situ hybridization veriifed that microRNA-214 was located in the cytoplasm of dorsal root ganglia primary neurons and was downregulated following sciatic nerve transection. Moreover, a com-bination of in situ hybridization and immunohistochemistry revealed that microRNA-214 and Slit-Robo GTPase-activating protein 3 were co-localized in dorsal root ganglion primary neu-rons. Western blot analysis suggested that Slit-Robo GTPase-activating protein 3 was upregulated in dorsal root ganglion neurons after sciatic nerve transection. These data demonstrate that mi-croRNA-214 is located and differentially expressed in dorsal root ganglion primary neurons and may participate in regulating the gene expression of Slit-Robo GTPase-activating protein 3 after sciatic nerve transection.

关键词： nerve regeneration peripheral nerve injury sciatic nerve injury Slit-Robo GTPase-activating protein 3 microRNA-214 dorsal root ganglia gene expression microarray bioinformatics NSFC grant neural regeneration

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Inhibitor of DNA binding 2 accelerates nerve regeneration after sciatic nerve injury in mice

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Neural Regeneration Research 2021年第12期16卷 2542-2548页

作者： Zhong-Hai Huang Ai-Ying Feng Jing Liu Libing Zhou Bing Zhou Panpan Yu Guangdong-Hong Kong-Macao Institute of Central Nervous System Regeneration Ministry of Education Joint International Research Laboratory of Central Nervous System RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina Interdisciplinary Innovation Institute of Medicine and Engineering Beijing Advanced Innovation Center for Big Data-Based Precision MedicineBeihang UniversityBeijingChina

Inhibitor of DNA binding 2(Id2)can promote axonal regeneration after injury of the central nervous system.However,whether Id2 can promote axonal regeneration and functional recovery after peripheral nerve injury is currently unknown.In this study,we established a mouse model of bilateral sciatic nerve crush injury.Two weeks before injury,AAV9-Id2-3×Flag-GFP was injected stereotaxically into the bilateral ventral horn of lumbar spinal cord.Our results showed that Id2 was successfully delivered into spinal cord motor neurons projecting to the sciatic nerve,and the number of regenerated motor axons in the sciatic nerve distal to the crush site was increased at 2 weeks after injury,arriving at the tibial nerve and reinnervating a few endplates in the gastrocnemius muscle.By 1 month after injury,extensive neuromuscular reinnervation occurred.In addition,the amplitude of compound muscle action potentials of the gastrocnemius muscle was markedly recovered,and their latency was shortened.These findings suggest that Id2 can accelerate axonal regeneration,promote neuromuscular reinnervation,and enhance functional improvement following sciatic nerve injury.Therefore,elevating the level of Id2 in adult neurons may present a promising strategy for peripheral nerve repair following injury.The study was approved by the Experimental Animal Ethics Committee of Jinan University(approval No.20160302003)on March 2,2016.

关键词： axonal regeneration functional recovery inhibitor of DNA binding 2 motor neuron neuromuscular junctions peripheral nerve reinnervation sciatic nerve injury

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