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Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord 被引量:1
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作者 Emily A.Hibbard Liwen Zhou +5 位作者 Cathy Z.Yang Karthik Venkudusamy Yessenia Montoya Alexa Olivarez George D.Bittner Dale R.Sengelaub 《Neural Regeneration Research》 SCIE CAS 2025年第7期2095-2107,共13页
Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically poor.We used a plasmalemmal fusogen,polyethylene g... Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically poor.We used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic nerves.We have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor recovery.Furthermore,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target muscles.In this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic nerve.Young adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of PEG.Compound action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury site.The success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days postoperatively.At 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish peroxidase.PEG-fusion repair reestablished axonal continuity.Compared to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal areas.Unexpectedly,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repair.This central reorganization may contribute to the improved behavioral recovery seen after PEG-fusion repair,supporting the use of this novel repair methodology over currently available treatments. 展开更多
关键词 AXOTOMY dorsal horn peripheral nerve injury PLASTICITY polyethylene glycol(PEG) sciatic nerve sensory terminals wheat germ agglutinin horseradish peroxidase
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EZH2-dependent myelination following sciatic nerve injury
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作者 Hui Zhu Li Mu +8 位作者 Xi Xu Tianyi Huang Ying Wang Siyuan Xu Yiting Wang Wencong Wang Zhiping Wang Hongkui Wang Chengbin Xue 《Neural Regeneration Research》 SCIE CAS 2025年第8期2382-2394,共13页
Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that ... Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that of native myelin.Silencing of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in vitro.To further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were generated.Our results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain unmyelinated.This highlights the crucial role of Ezh2 in initiating Schwann cell myelination.Furthermore,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type littermates.This suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and remyelination.In conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve injury.Modulating EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries. 展开更多
关键词 DEMYELINATION EZH2 MYELINATION peripheral nerve injury PRC2 REMYELINATION Schwann cells sciatic nerve crush sciatic nerve transection
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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve
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作者 Carina Hromada Patrick Heimel +10 位作者 Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher 《Neural Regeneration Research》 SCIE CAS 2025年第6期1789-1800,共12页
Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the ... Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use. 展开更多
关键词 axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit VASCULARIZATION
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Concomitant treatment of ureteral calculi and ipsilateral pelvic sciatic nerve schwannoma with transperitoneal laparoscopic approach: A case report
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作者 Yang Xiong Jin Li Han-Jie Yang 《World Journal of Clinical Cases》 SCIE 2024年第11期1947-1953,共7页
BACKGROUND Schwannomas are rare peripheral neural myelin sheath tumors that originate from Schwann cells.Of the different types of schwannomas,pelvic sciatic nerve schwannoma is extremely rare.Definite preoperative di... BACKGROUND Schwannomas are rare peripheral neural myelin sheath tumors that originate from Schwann cells.Of the different types of schwannomas,pelvic sciatic nerve schwannoma is extremely rare.Definite preoperative diagnosis of pelvic schwannomas is difficult,and surgical resection is the gold standard for its definite diagnosis and treatment.CASE SUMMARY We present a case of pelvic schwannoma arising from the sciatic nerve that was detected in a 40-year-old man who underwent computed tomography for intermittent right lower back pain caused exclusively by a right ureteral calculus.Subsequently,successful transperitoneal laparoscopic surgery was performed for the intact removal of the stone and en bloc resection of the schwannoma.The total operative time was 125 min,and the estimated blood loss was inconspicuous.The surgical procedure was uneventful.The patient was discharged on postoperative day 5 with the simultaneous removal of the urinary catheter.However,the patient presented with motor and sensory disorders of the right lower limb,caused by partial damage to the right sciatic nerve.No tumor recurrence was observed at the postoperative appointment.CONCLUSION Histopathological examination of the specimen confirmed the diagnosis of a schwannoma.Thus,laparoscopic surgery is safe and feasible for concomitant extirpation of pelvic schwannomas and other pelvic and abdominal diseases that require surgical treatment. 展开更多
关键词 SCHWANNOMA sciatic nerve Laparoscopy Ureteral calculi Pelvic neoplasms Case report
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Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury 被引量:2
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作者 Yuhui Kou Yusong Yuan +3 位作者 Qicheng Li Wenyong Xie Hailin Xu Na Han 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第8期1822-1827,共6页
Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide ... Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The 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 assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The 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 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,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. 展开更多
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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Chemokine platelet factor 4 accelerates peripheral nerve regeneration by regulating Schwann cell activation and axon elongation 被引量:1
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作者 Miao Gu Xiao Cheng +3 位作者 Di Zhang Weiyan Wu Yi Cao Jianghong He 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期190-195,共6页
Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and foun... Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury. 展开更多
关键词 axon elongation bioinformatic analysis cell migration cell proliferation dorsal root ganglia peripheral nerve regeneration peripheral nerve trauma platelet factor 4 rat sciatic nerve Schwann cells
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A hyaluronic acid granular hydrogel nerve guidance conduit promotes regeneration and functional recovery of injured sciatic nerves in rats 被引量:4
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作者 Jie Yang Chia-Chen Hsu +3 位作者 Ting-Ting Cao Hua Ye Jing Chen Yun-Qing Li 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第3期657-663,共7页
A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regen... A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration.However,in vivo experiments have not been conducted.In this study,we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap.The Basso,Beattie,and Bresnahan locomotor rating scale,sciatic nerve compound muscle action potential recording,Fluoro-Gold retrograde tracing,growth related protein 43/S100 immunofluorescence staining,transmission electron microscopy,gastrocnemius muscle dry/wet weight ratio,and Masson’s trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath,and recovery of the electrophysiological function and motor function as autologous nerve transplantation.The conduit results were superior to those of a bulk hydrogel or silicone tube transplant.These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve.The nerve conduits have the potential as a material for repairing peripheral nerve defects. 展开更多
关键词 functional recovery granular hydrogel hyaluronic acid myelin sheath nerve conduit nerve regeneration peripheral nerve regeneration sciatic nerve injury tissue engineering transection injury
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Platelet-rich plasma promotes peripheral nerve regeneration after sciatic nerve injury 被引量:3
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作者 Su-Long Wang Xi-Lin Liu +1 位作者 Zhi-Chen Kang Yue-Shu Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第2期375-381,共7页
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 pla... 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. 展开更多
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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Autophagy-targeting modulation to promote peripheral nerve regeneration
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作者 Yan Chen Hongxia Deng Nannan Zhang 《Neural Regeneration Research》 SCIE CAS 2025年第7期1864-1882,共19页
Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulat... Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies. 展开更多
关键词 AUTOPHAGY autophagy related genes Charcot–Marie–Tooth diseases diabetic peripheral neuropathy METFORMIN MYELINATION peripheral nerve injury Schwann cells sciatic nerve Wallerian degeneration
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Chitosan conduits enriched with fibrin-collagen hydrogel with or without adipose-derived mesenchymal stem cells for the repair of 15-mm-long sciatic nerve defect 被引量:1
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作者 Marwa El Soury óscar Darío García-García +6 位作者 Isabella Tarulli Jesús Chato-Astrain Isabelle Perroteau Stefano Geuna Stefania Raimondo Giovanna Gambarotia Víctor Carriel 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第6期1378-1385,共8页
Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Holl... Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair.Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance.In this study,we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model.Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks.Nevertheless,the molecular assessment in the early regeneration phase(7,14,and 28 days)has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones.Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1,a growth factor that plays an important role in Schwann cell transdifferentiation.The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2,VEGF-A,BDNF,c-Jun,and ATF3. 展开更多
关键词 adipose-derived stem cells chitosan conduit fibrin and collagen hydrogel nerve regeneration nerve repair neuregulin 1 peripheral nerve sciatic nerve
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Application Research of PETD Combined with MRI Nerve Root Water Imaging in the Minimally Invasive Treatment of LDH
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作者 Guanhua Wang Zhe Shen +4 位作者 Jinben Yu Shengjie Xu Weinan Xu Bing Xu Xiaoyu Ye 《International Journal of Clinical Medicine》 CAS 2024年第4期167-176,共10页
Objective: This study aims to evaluate the safety and efficacy of PETD combined with nerve root water imaging of MRI for the treatment of lumbar disc herniation. Methods: A retrospective review was performed on 62 pat... Objective: This study aims to evaluate the safety and efficacy of PETD combined with nerve root water imaging of MRI for the treatment of lumbar disc herniation. Methods: A retrospective review was performed on 62 patients with lumbar disc herniation from March 2019 to March 2021. The study included an experimental group of 30 patients and a control group of 32 patients. The experimental group underwent PETD combined with nerve root water imaging of MRI, while the control group received traditional PETD treatment. The visual analogue scoring method (VAS score), and JOA lumbar spine function score before and after surgery were compared between the two groups, and efficacy was assessed and compared using the MacNab score. Results: The mean operation time was significantly reduced in the experimental group (56.43 &#177;10.40 minutes) compared to the control group (65.69 &#177;14.12 minutes). The VAS score was compared between the two groups with preoperative (p = 0.624), one month after surgery (p = 0.325), three months after surgery (p = 0.676), one year after surgery (p = 0.341);The JOA score was compared between the two groups with preoperative (p = 0.961), one month after the surgery (p = 0.266), three months after surgery (p = 0.185), one year after surgery (p = 0.870), they were no significant statistical difference;The efficacy evaluation of the last follow-up Macnab showed that all the 30 patients in the experimental group were excellent, 31 of 32 patients in the control group were excellent, 1 case was good;There was no statistical difference in the comparison between the two groups (p > 0.05). Conclusion: The study concludes that the combined approach of PETD with nerve root water imaging of MRI is a safe, effective, and more efficient alternative to conventional PETD for treating lumbar disc herniation. 展开更多
关键词 Lumbar Disc Herniation nerve Root Water Imaging Percutaneous Interforaminal Endoscopy Minimally Invasive Spine surgery DISCECTOMY
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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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作者 WANG Bin Bin GUO Chao +6 位作者 SUN Sheng Qiao ZHANG Xing Nan LI Zhen LI Wei Jie LI De Zhi SCHUMACHER Michael LIU Song 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2023年第2期160-173,共14页
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 an... 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. 展开更多
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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作者 YANG GU MINGGUANG BI +2 位作者 DEHUI CHEN NING NI JIANMING CHEN 《BIOCELL》 SCIE 2023年第9期2069-2080,共12页
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 compres... 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 theoretical basis for the development of therapeutic targets for SNI. 展开更多
关键词 Oxygen glucose deprivation PROTEOMICS sciatic nerve injury Peripheral nerve injury
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Charcot-Marie-Tooth-1A and sciatic nerve crush rat models:insights from proteomics
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作者 Zeina Msheik Stephanie Durand +5 位作者 Emilie Pinault Martial Caillaud Laetitia Vignaud Fabrice Billet Mohamed El Massry Alexis Desmoulière 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第6期1354-1363,共10页
The sensorimotor and histological aspects of peripheral neuropathies were already studied by our team in two rat models:the sciatic nerve crush and the Charcot-Marie-Tooth-1A disease.In this study,we sought to highlig... The sensorimotor and histological aspects of peripheral neuropathies were already studied by our team in two rat models:the sciatic nerve crush and the Charcot-Marie-Tooth-1A disease.In this study,we sought to highlight and compare the protein signature of these two pathological situations.Indeed,the identification of protein profiles in diseases can play an important role in the development of pharmacological targets.In fact,Charcot-Marie-Tooth-1A rats develop motor impairments that are more severe in the hind limbs.Therefore,for the first time,protein expression in sciatic nerve of Charcot-Marie-Tooth-1A rats was examined.First,distal sciatic nerves were collected from Charcot-Marie-Tooth-1A and uninjured wild-type rats aged 3 months.After protein extraction,sequential window acquisition of all theoretical fragment ion spectra liquid chromatography and mass spectrometry was employed.445 proteins mapped to Swiss-Prot or trEMBL Uniprot databases were identified and quantified.Of these,153 proteins showed statistically significant differences between Charcot-Marie-Tooth-1A and wild-type groups.The majority of these proteins were overexpressed in Charcot-Marie-Tooth-1A.Hierarchical clustering and functional enrichment using Gene Ontology were used to group these proteins based on their biological effects concerning Charcot-Marie-Tooth-1A pathophysiology.Second,proteomic characterization of wild-type rats subjected to sciatic nerve crush was performed sequential window acquisition of all theoretical fragment ion spectra liquid chromatography and mass spectrometry.One month after injury,distal sciatic nerves were collected and analyzed as described above.Out of 459 identified proteins,92 showed significant differences between sciatic nerve crush and the uninjured wild-type rats used in the first study.The results suggest that young adult Charcot-Marie-Tooth-1A rats(3 months old)develop compensatory mechanisms at the level of redox balance,protein folding,myelination,and axonogenesis.These mechanisms seem insufficient to hurdle the progress of the disease.Notably,response to oxidative stress appears to be a significant feature of Charcot-Marie-Tooth-1A,potentially playing a role in the pathological process.In contrast to the first experiment,the majority of the proteins that differed from wild-type were downregulated in the sciatic nerve crush group.Functional enrichment suggested that neurogenesis,response to axon injury,and oxidative stress were important biological processes.Protein analysis revealed an imperfect repair at this time point after injury and identified several distinguishable proteins.In conclusion,we suggest that peripheral neuropathies,whether of a genetic or traumatic cause,share some common pathological pathways.This study may provide directions for better characterization of these models and/or identifying new specific therapeutic targets. 展开更多
关键词 Charcot-Marie-Tooth-1A endoplasmic reticulum Gene Ontology NEUROGENESIS oxidative stress PROTEOMICS rat repair sciatic nerve crush SWATH-MS
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Combined Sciatic, Femoral, and Obturator Nerve Blocks for Ankle Surgery in a Patient with Severe Pulmonary Hypertension—A Case Report 被引量:1
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作者 Ju Hyun Lee Hyun Su Shin +2 位作者 Ki Yoon Kim Ji Seon Jeong Justin Sangwook Ko 《Open Journal of Anesthesiology》 2017年第8期203-209,共7页
We report a patient with severe pulmonary arterial hypertension (PAH) undergoing tibio-talo-calcaneal fusion due to Charcot joint. Despite the advancement in the management of PAH, the risks of anesthesia, surgery, an... We report a patient with severe pulmonary arterial hypertension (PAH) undergoing tibio-talo-calcaneal fusion due to Charcot joint. Despite the advancement in the management of PAH, the risks of anesthesia, surgery, and postoperative morbidity and mortality still remain high. A 46-year-old female was presented with severe PAH and end stage renal disease requiring hemodialysis three times a week. Ultrasound-guided sciatic, femoral, and obturator nerve blocks were performed with 0.5% levobupivacaine 15 ml, 10 ml, and 5 ml, respectively. All the blocks were successful, and the patient underwent uneventful anesthesia and surgery. In addition, the postoperative pain control lasted for 15 h and the patient was discharged on POD 5 without any complications. Therefore, ultrasound-guided sciatic, femoral, and obturator nerve blocks are valuable alternative to the general or neuraxial anesthesia in patients with severe pulmonary hypertension. 展开更多
关键词 FEMORAL nerve BLOCK OBTURATOR nerve BLOCK sciatic nerve BLOCK Severe Pulmonary Hypertension ULTRASOUND-GUIDED
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Nerve growth factor-basic fibroblast growth factor poly-lactide co-glycolid sustained-release microspheres and the small gap sleeve bridging technique to repair peripheral nerve injury 被引量:3
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作者 Ming Li Ting-Min Xu +7 位作者 Dian-Ying Zhang Xiao-Meng Zhang Feng Rao Si-Zheng Zhan Man Ma Chen Xiong Xiao-Feng Chen Yan-Hua Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第1期162-169,共8页
We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role... We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level. 展开更多
关键词 biomimetic microfluidic chip growth factor in vitro biomimetic microenvironment nerve function peripheral nerve injury sciatic nerve small gap sleeve bridging sustained-release microspheres
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Repair and regeneration of peripheral nerve injuries that ablate branch points 被引量:1
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作者 JuliAnne E.Allgood George D.Bittner Jared S.Bushman 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第12期2564-2568,共5页
The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS h... The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS have been extensively studied and routinely treated with autografts, acellular nerve allografts, conduits, wraps, and nerve transfers. In contrast, segmental-loss peripheral nerve injuries, in which one or more branch points are ablated so that there are three or more nerve endings, present additional complications that have not been rigorously studied or documented. This review discusses:(1) the branched anatomy of the peripheral nervous system,(2) case reports describing how peripheral nerve injuries with branched ablations have been surgically managed,(3) factors known to influence regeneration through branched nerve structures,(4) techniques and models of branched peripheral nerve injuries in animal models, and(5) conclusions regarding outcome measures and studies needed to improve understanding of regeneration through ablated branched structures of the peripheral nervous system. 展开更多
关键词 ALLOGRAFT animal model branched injuries femoral nerve peripheral nerve injury peripheral nervous system REGENERATION REPAIR sciatic nerve surgical repair
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Long noncoding RNA H19 regulates degeneration and regeneration of injured peripheral nerves 被引量:1
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作者 Yu-Mei Feng Jian Shao +6 位作者 Min Cai Yi-Yue Zhou Yi Yao Jia-Xi Qian Zi-Han Ding Mao-Rong Jiang Deng-Bing Yao 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第8期1847-1851,共5页
Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows... Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons.However,the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear.In this study,we established a Sprague-Dawley rat model of sciatic nerve transection injury.We performed in situ hybridization and found that at 4–7 days after sciatic nerve injury,lncRNA H19 was highly expressed.At 14 days before injury,adeno-associated virus was intrathecally injected into the L4–L5 foramina to disrupt or overexpress lncRNA H19.After overexpression of lncRNA H19,the growth of newly formed axons from the sciatic nerve was inhibited,whereas myelination was enhanced.Then,we performed gait analysis and thermal pain analysis to evaluate rat behavior.We found that lncRNA H19 overexpression delayed the recovery of rat behavior function,whereas interfering with lncRNA H19 expression improved functional recovery.Finally,we examined the expression of lncRNA H19 downstream target SEMA6D,and found that after lncRNA H19 overexpression,the SEMA6D protein level was increased.These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves.This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration. 展开更多
关键词 adeno-associated virus dorsal root ganglion lncRNA H19 nerve degeneration nerve regeneration peripheral nerve rat sciatic nerve injury semaphorin 6D Wallerian degeneration
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Electroacupuncture and moxibustion promote regeneration of injured sciatic nerve through Schwann cell proliferation and nerve growth factor secretion 被引量:24
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作者 Lin-na Hu Jin-xin Tian +7 位作者 Wei Gao Jing Zhu Fang-fang Mou Xiao-chun Ye Yu-pu Liu Ping-ping Lu Shui-jin Shao Hai-dong Guo 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第3期477-483,共7页
Using electroacupuncture and moxibustion to treat peripheral nerve injury is highly efficient with low side effects. However, the electroacupuncture-and moxibustion-based mechanisms underlying nerve repair are still u... Using electroacupuncture and moxibustion to treat peripheral nerve injury is highly efficient with low side effects. However, the electroacupuncture-and moxibustion-based mechanisms underlying nerve repair are still unclear. Here, in vivo and in vitro experiments uncovered one mechanism through which electroacupuncture and moxibustion affect regeneration after peripheral nerve injury. We first established rat models of sciatic nerve injury using neurotomy. Rats were treated with electroacupuncture or moxibustion at acupoints Huantiao (GB30) and Zusanli (ST36). Each treatment lasted 15 minutes, and treatments were given six times a week for 4 consecutive weeks. Behavioral testing was used to determine the sciatic functional index. We used electrophysiological detection to measure sciatic nerve conduction velocity and performed hematoxylin-eosin staining to determine any changes in the gastrocnemius muscle. We used immunohistochemistry to observe changes in the expression of S100—a specific marker for Schwann cells—and an enzyme-linked immunosorbent assay to detect serum level of nerve growth factor. Results showed that compared with the model-only group, sciatic functional index, recovery rate of conduction velocity, diameter recovery of the gastrocnemius muscle fibers, number of S100-immunoreactive cells,and level of nerve growth factor were greater in the electroacupuncture and moxibustion groups. The efficacy did not differ between treatment groups. The serum from treated rats was collected and used to stimulate Schwann cells cultured in vitro. Results showed that the viability of Schwann cells was much higher in the treatment groups than in the model group at 3 and 5 days after treatment. These findings indicate that electroacupuncture and moxibustion promoted nerve regeneration and functional recovery; its mechanism might be associated with the enhancement of Schwann cell proliferation and upregulation of nerve growth factor. 展开更多
关键词 nerve regeneration peripheral nerve injury electroacupuncture moxibustion acupuncture serum Schwann cells nerve growth factor PROLIFERATION REGENERATION sciatic functional index neural regeneration
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Combination of olfactory ensheathing cells and human umbilical cord mesenchymal stem cell-derived exosomes promotes sciatic nerve regeneration 被引量:15
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作者 Yang Zhang Wen-Tao Wang +2 位作者 Chun-Rong Gong Chao Li Mei Shi 《Neural Regeneration Research》 SCIE CAS CSCD 2020年第10期1903-1911,共9页
Olfactory ensheathing cells(OECs)are promising seed cells for nerve regeneration.However,their application is limited by the hypoxic environment usually present at the site of injury.Exosomes derived from human umbili... Olfactory ensheathing cells(OECs)are promising seed cells for nerve regeneration.However,their application is limited by the hypoxic environment usually present at the site of injury.Exosomes derived from human umbilical cord mesenchymal stem cells have the potential to regulate the pathological processes that occur in response to hypoxia.The ability of OECs to migrate is unknown,especially in hypoxic conditions,and the effect of OECs combined with exosomes on peripheral nerve repair is not clear.Better understanding of these issues will enable the potential of OECs for the treatment of nerve injury to be addressed.In this study,OECs were acquired from the olfactory bulb of Sprague Dawley rats.Human umbilical cord mesenchymal stem cell-derived exosomes(0–400μg/mL)were cultured with OECs for 12–48 hours.After culture with 400μg/mL exosomes for 24 hours,the viability and proliferation of OECs were significantly increased.We observed changes to OECs subjected to hypoxia for 24 hours and treatment with exosomes.Exosomes significantly promoted the survival and migration of OECs in hypoxic conditions,and effectively increased brain-derived neurotrophic factor gene expression,protein levels and secretion.Finally,using a 12 mm left sciatic nerve defect rat model,we confirmed that OECs and exosomes can synergistically promote motor and sensory function of the injured sciatic nerve.These findings show that application of OECs and exosomes can promote nerve regeneration and functional recovery.This study was approved by the Institutional Ethical Committee of the Air Force Medical University,China(approval No.IACUC-20181004)on October 7,2018;and collection and use of human umbilical cord specimens was approved by the Ethics Committee of the Linyi People’s Hospital,China(approval No.30054)on May 20,2019. 展开更多
关键词 brain-derived neurotrophic factor cell migration cell viability functional recovery HYPOXIA nerve regeneration sciatic functional index sciatic nerve injury
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