After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the tim...After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.展开更多
The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiot...The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiota is crucial for several functions,including host metabolism,physiology,maintenance of the intestinal epithelial integrity,nutrition,and immune function,earning it the designation of a“vital organ”(Guinane and Cotter,2013).展开更多
Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,...Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,this may lead to permanent impairements resulting in a loss of quality of life and a high socioeconomic burden.展开更多
The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral bloo...The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.展开更多
Corrigendum:Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway https://doi.org/10.4103/NRR.NRR-D-25-00562 In the article titled“Epalrestat protect...Corrigendum:Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway https://doi.org/10.4103/NRR.NRR-D-25-00562 In the article titled“Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway,”published on pages 345-351 in Issue 2,Volume 11 of Neural Regeneration Research(Li et al.,2016),the Western blot bands in Figure 2A are incorrect.展开更多
Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practic...Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practice show poor targeting,rapid drug clearance from the circulatory system,and low therapeutic efficiency.Therefore,in this review,we have first described the mechanisms underlying nerve regeneration,characterized the biomaterials used for drug delivery to facilitate nerve regeneration,and highlighted the functionalization strategies used for such drug-delivery systems.These systems mainly use natural and synthetic polymers,inorganic materials,and hybrid systems with advanced drug-delivery abilities,including nanoparticles,hydrogels,and scaffoldbased systems.Then,we focused on comparing the types of drug-delivery systems for neural regeneration as well as the mechanisms and challenges associated with targeted delivery of drugs to facilitate neural regeneration.Finally,we have summarized the clinical application research and limitations of targeted delivery of these drugs.These biomaterials and drug-delivery systems can provide mechanical support,sustained release of bioactive molecules,and enhanced intercellular contact,ultimately reducing cell apoptosis and enhancing functional recovery.Nevertheless,immune reactions,degradation regulation,and clinical translations remain major unresolved challenges.Future studies should focus on optimizing biomaterial properties,refining delivery precision,and overcoming translational barriers to advance these technologies toward clinical applications.展开更多
Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological prop...Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.展开更多
Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography...Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).展开更多
Background:Inflammation,caused by prolonged hyperglycemia,plays a substantially more important part in the progression of diabetic peripheral neuropathy(DPN).Notably,the MAPK pathway that mediates the Nuclear Factor-k...Background:Inflammation,caused by prolonged hyperglycemia,plays a substantially more important part in the progression of diabetic peripheral neuropathy(DPN).Notably,the MAPK pathway that mediates the Nuclear Factor-kappa B(NF-κB)pathway contributes to inflammation-induced peripheral nerve damage,affecting cell survival.Juan Bi Tong Luo(JBTL),a traditional Chinese medicine(TCM),has demonstrated favorable results in alleviating pain and numbness in patients with DPN;however,whether JBTL exerts its effect through the MAPK mediating NF-κB pathway remains unclear.Methods:This study investigated whether JBTL modulates apoptosis in DPN models and Schwann cells cultured in 100 mM of glucose by MAPK/NF-κB.Results:The JBTL altered inflammation,reduced peripheral nerve tissue damage,and improved cell survival rates by down-regulating MAPK/NF-κB.Conclusion:Our findings demonstrate that the effect of JBTL on DPN is likely mediated by suppressing inflammation induced by the MAPK/NF-κB pathway,thus providing evidence for the clinical efficacy of JBTL in treating DPN.展开更多
Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kines...Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.展开更多
Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are...Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are incomplete and spare supraspinal pathways,especially those located within the peripheral white matter of the spinal cord,which includes reticulospinal pathways originating from the medullary reticular formation.Whereas there is abundant literature about the motor cortex,its corticospinal pathway,and its capacity to modulate functional recovery after SCI,less is known about the medullary reticular formation and its reticulospinal pathway.展开更多
Central nervous system(CNS) axons fail to regenerate following brain or spinal cord injury(SCI),which typically leads to permanent neurological deficits.Peripheral nervous system axons,howeve r,can regenerate followin...Central nervous system(CNS) axons fail to regenerate following brain or spinal cord injury(SCI),which typically leads to permanent neurological deficits.Peripheral nervous system axons,howeve r,can regenerate following injury.Understanding the mechanisms that underlie this difference is key to developing treatments for CNS neurological diseases and injuries characterized by axonal damage.To initiate repair after peripheral nerve injury,dorsal root ganglion(DRG) neurons mobilize a pro-regenerative gene expression program,which facilitates axon outgrowth.展开更多
Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells en...Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells encounter various obstacles,including limited tissue sources,invasive acquisition methods,cellular heterogeneity,purification challenges,cellular senescence,and diminished pluripotency and proliferation over successive passages.In this study,we used induced pluripotent stem cell-derived mesenchymal stem cells,known for their self-renewal capacity,multilineage differentiation potential,and immunomodulatory characteristics.We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury.Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation.Furthermore,the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats.Additionally,our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization.Collectively,our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats,offering promising therapeutic strategies for clinical translation.展开更多
Neural machine interface technology is a pioneering approach that aims to address the complex challenges of neurological dysfunctions and disabilities resulting from conditions such as congenital disorders,traumatic i...Neural machine interface technology is a pioneering approach that aims to address the complex challenges of neurological dysfunctions and disabilities resulting from conditions such as congenital disorders,traumatic injuries,and neurological diseases.Neural machine interface technology establishes direct connections with the brain or peripheral nervous system to restore impaired motor,sensory,and cognitive functions,significantly improving patients'quality of life.This review analyzes the chronological development and integration of various neural machine interface technologies,including regenerative peripheral nerve interfaces,targeted muscle and sensory reinnervation,agonist–antagonist myoneural interfaces,and brain–machine interfaces.Recent advancements in flexible electronics and bioengineering have led to the development of more biocompatible and highresolution electrodes,which enhance the performance and longevity of neural machine interface technology.However,significant challenges remain,such as signal interference,fibrous tissue encapsulation,and the need for precise anatomical localization and reconstruction.The integration of advanced signal processing algorithms,particularly those utilizing artificial intelligence and machine learning,has the potential to improve the accuracy and reliability of neural signal interpretation,which will make neural machine interface technologies more intuitive and effective.These technologies have broad,impactful clinical applications,ranging from motor restoration and sensory feedback in prosthetics to neurological disorder treatment and neurorehabilitation.This review suggests that multidisciplinary collaboration will play a critical role in advancing neural machine interface technologies by combining insights from biomedical engineering,clinical surgery,and neuroengineering to develop more sophisticated and reliable interfaces.By addressing existing limitations and exploring new technological frontiers,neural machine interface technologies have the potential to revolutionize neuroprosthetics and neurorehabilitation,promising enhanced mobility,independence,and quality of life for individuals with neurological impairments.By leveraging detailed anatomical knowledge and integrating cutting-edge neuroengineering principles,researchers and clinicians can push the boundaries of what is possible and create increasingly sophisticated and long-lasting prosthetic devices that provide sustained benefits for users.展开更多
Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration vi...Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.展开更多
“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal cord.Peripheral nerve injury results in movements or sensation impairments,and represents a serious public health pro...“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal cord.Peripheral nerve injury results in movements or sensation impairments,and represents a serious public health problem.Although severed peripheral nerves have been effectively joined and various therapies have been offered,recovery of sensory or motor functions remains limited,and efficacious therapies for complete repair of a nerve injury remain elusive.The emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and function.Mesenchymal stem cells,as large living cells responsive to the environment,secrete various factors and exosomes.The latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins,microRNA,and messenger RNA derived from parent mesenchymal stem cells.Exosomes have pivotal roles in cell-to-cell communication and nervous tissue function,offering solutions to changes associated with cell-based therapies.Despite ongoing investigations,mesenchymal stem cells and mesenchymal stem cell-derived exosome-based therapies are in the exploratory stage.A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical translation.This review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in peripheral nerve injury,exploring the underlying mechanisms.Subsequently,it provides an overview of the current status of mesenchymal stem cell and exosomebased therapies in clinical trials,followed by a comparative analysis of therapies utilizing mesenchymal stem cells and exosomes.Finally,the review addresses the limitations and challenges associated with use of mesenchymal stem cell-derived exosomes,offering potential solutions and guiding future directions.展开更多
Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes...Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.展开更多
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
Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduit...Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.展开更多
Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve rep...Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.展开更多
基金supported by the National Key Research and Development Program of China,No.2023YFC3603705(to DX)the National Natural Science Foundation of China,No.82302866(to YZ).
文摘After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.
基金supported by the European Union-Next Generation EU,Mission 4 Component 1,Project Title:“Gut and Neuro Muscular system:investigating the impact of microbiota on nerve regeneration and muscle reinnervation after peripheral nerve injury”,CUP D53D23007770006,MUR:20227YB93W,to GR。
文摘The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiota is crucial for several functions,including host metabolism,physiology,maintenance of the intestinal epithelial integrity,nutrition,and immune function,earning it the designation of a“vital organ”(Guinane and Cotter,2013).
文摘Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,this may lead to permanent impairements resulting in a loss of quality of life and a high socioeconomic burden.
基金supported by Department of Defense grant HT9425-24-1-0030 a grant from the Stanley Medical Research Institute(to SS).
文摘The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.
文摘Corrigendum:Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway https://doi.org/10.4103/NRR.NRR-D-25-00562 In the article titled“Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway,”published on pages 345-351 in Issue 2,Volume 11 of Neural Regeneration Research(Li et al.,2016),the Western blot bands in Figure 2A are incorrect.
基金the support from Base for Interdisciplinary Innovative Talent Training,Shanghai Jiao Tong UniversityYouth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine。
文摘Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practice show poor targeting,rapid drug clearance from the circulatory system,and low therapeutic efficiency.Therefore,in this review,we have first described the mechanisms underlying nerve regeneration,characterized the biomaterials used for drug delivery to facilitate nerve regeneration,and highlighted the functionalization strategies used for such drug-delivery systems.These systems mainly use natural and synthetic polymers,inorganic materials,and hybrid systems with advanced drug-delivery abilities,including nanoparticles,hydrogels,and scaffoldbased systems.Then,we focused on comparing the types of drug-delivery systems for neural regeneration as well as the mechanisms and challenges associated with targeted delivery of drugs to facilitate neural regeneration.Finally,we have summarized the clinical application research and limitations of targeted delivery of these drugs.These biomaterials and drug-delivery systems can provide mechanical support,sustained release of bioactive molecules,and enhanced intercellular contact,ultimately reducing cell apoptosis and enhancing functional recovery.Nevertheless,immune reactions,degradation regulation,and clinical translations remain major unresolved challenges.Future studies should focus on optimizing biomaterial properties,refining delivery precision,and overcoming translational barriers to advance these technologies toward clinical applications.
基金supported by the Shenzhen Hong Kong Joint Funding Project,No.SGDX20230116093645007(to LY)the Shenzhen Science and Technology Innovation Committee International Cooperation Project,No.GJHZ20200731095608025(to LY)+7 种基金Shenzhen Development and Reform Commission’s Intelligent Diagnosis,Treatment and Prevention of Adolescent Spinal Health Public Service Platform,No.S2002Q84500835(to LY)Shenzhen Medical Research Fund,No.B2303005(to LY)Team-based Medical Science Research Program,No.2024YZZ02(to LY)Zhejiang Provincial Natural Science Foundation of China,No.LWQ20H170001(to RL)Basic Research Project of Shenzhen Science and Technology from Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324103010029(to BY)Shenzhen Second People’s Hospital Clinical Research Fund of Guangdong Province High-level Hospital Construction Project,Nos.2023yjlcyj029(to BY),2023yjlcyj021(to LL)Guangdong Basic and Applied Basic Research Foundation,No.2022A1515110679(to LL)China Postdoctoral Science Foundation,No.2022M722203(to GL).
文摘Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.
文摘Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).
基金funded by grants from the Suzhou Gusu Health Talents Project(grant No.GSWS2024050 to Liu W)Natural Science Foundation Project of Nanjing University of Chinese Medicine(grant No.XZR2021043 to Liu W and grant No.XZR2023021 to Huang F)+1 种基金Suzhou Science Education Health Youth Project(grant No.KJXW2021046 to Liu W)Suzhou Major Disease Multi-center Clinical Research Project(grant No.DZXYJ202410 to Huang F).
文摘Background:Inflammation,caused by prolonged hyperglycemia,plays a substantially more important part in the progression of diabetic peripheral neuropathy(DPN).Notably,the MAPK pathway that mediates the Nuclear Factor-kappa B(NF-κB)pathway contributes to inflammation-induced peripheral nerve damage,affecting cell survival.Juan Bi Tong Luo(JBTL),a traditional Chinese medicine(TCM),has demonstrated favorable results in alleviating pain and numbness in patients with DPN;however,whether JBTL exerts its effect through the MAPK mediating NF-κB pathway remains unclear.Methods:This study investigated whether JBTL modulates apoptosis in DPN models and Schwann cells cultured in 100 mM of glucose by MAPK/NF-κB.Results:The JBTL altered inflammation,reduced peripheral nerve tissue damage,and improved cell survival rates by down-regulating MAPK/NF-κB.Conclusion:Our findings demonstrate that the effect of JBTL on DPN is likely mediated by suppressing inflammation induced by the MAPK/NF-κB pathway,thus providing evidence for the clinical efficacy of JBTL in treating DPN.
基金supported by the Portuguese Foundation for Science and Technology(FCT),Centro 2020 and Portugol2020 and the EU FEDER program,via the project GoBack to SIV(PTDC/CVT-CVT/32261/2017,CENTRO-01-0145-FEDER-032261)the doctoral grants of PDC(SFRH/BD/139974/2018)and BMS(2020.06525.BD and DOI 10.54499/2020.06525.BD)+5 种基金the post-doctoral grant to JPF(SFRH/BPD/113359/2015-program-contract described in paragraphs 4,5,6 of art.23 of Law no.100157/2016,of August 29,as amended by Law no.57/2017 of July 2019),the project PTDC/MED-NEU/1677/2021 to JBRthe Institute of Biomedicine iBiMED(UIDB/04501/2020 and DOI 10.54499/UIDB/04501/2020,UIDP/04501/2020 and DOI 10.54499/UIDP/04501/2020)its LiM Bioimaging Facility-a PPBI node(POCI-01-0145-FEDER-022122)supported by the Research Commission of the Medical Faculty of the Heinrich-Heine-University(HHU)Düsseldorf,of the Biologisch-Medizinisches Forschungszentrum(BMFZ)of HHUfinanced by the Spanish"Plan Nacional de Investigacion Cientifica,Desarrollo e Innovacion Tecnologica,Ministerio de Economia y Competitividad(Instituto de Salud CarlosⅢ)",co-financed by the European Union(FEDER program),(grant FIS P/20/00318 and FIS P23/00337 to VC)grant CPP2021-009070 to VC by the"Proyectos de colaboracion publico-privada,Plan de Investigacion Cientifica,Tecnica y de inovacion 2021-2023,Ministerio de Ciencia e Innovacion,Union Europea,Agencia Estatal de Investigacion,Espana"。
文摘Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.
基金supported by Craig H.Neilsen Foundation,Wings for Life Foundation,Canadian Institutes of Health Research,and Fonds de Recherche Québec-Santé(to FB).
文摘Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are incomplete and spare supraspinal pathways,especially those located within the peripheral white matter of the spinal cord,which includes reticulospinal pathways originating from the medullary reticular formation.Whereas there is abundant literature about the motor cortex,its corticospinal pathway,and its capacity to modulate functional recovery after SCI,less is known about the medullary reticular formation and its reticulospinal pathway.
基金supported by the Canada Foundation for Innovation (Project#44220)the Natural Sciences and Engineering Research Council of Canada (RGPIN-2024-03986)+3 种基金the Michael Smith Foundation for Health Research BCthe financial support of Health Canada,through the Canada Brain Research Fund,an innovative partnership between the Government of Canada (through Health Canada),Brain Canada Foundationthe Azrieli Foundationsupported by a Canadian Institutes of Health Research (CIHR) Canada Graduate Scholarship–Master’s Award。
文摘Central nervous system(CNS) axons fail to regenerate following brain or spinal cord injury(SCI),which typically leads to permanent neurological deficits.Peripheral nervous system axons,howeve r,can regenerate following injury.Understanding the mechanisms that underlie this difference is key to developing treatments for CNS neurological diseases and injuries characterized by axonal damage.To initiate repair after peripheral nerve injury,dorsal root ganglion(DRG) neurons mobilize a pro-regenerative gene expression program,which facilitates axon outgrowth.
基金supported by the National Natural Science Foundation of China,No.32171356(to YW)Self-Support Research Projects of Shihezi University,No.ZZZC2021105(to WJ)+1 种基金Capital Medical University Natural Science Cultivation Fund,No.PYZ23044(to FQM)Beijing Municipal Natural Science Foundation,No.7244410(to JHD)。
文摘Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells encounter various obstacles,including limited tissue sources,invasive acquisition methods,cellular heterogeneity,purification challenges,cellular senescence,and diminished pluripotency and proliferation over successive passages.In this study,we used induced pluripotent stem cell-derived mesenchymal stem cells,known for their self-renewal capacity,multilineage differentiation potential,and immunomodulatory characteristics.We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury.Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation.Furthermore,the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats.Additionally,our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization.Collectively,our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats,offering promising therapeutic strategies for clinical translation.
基金supported in part by the National Natural Science Foundation of China,Nos.81927804(to GL),82260456(to LY),U21A20479(to LY)Science and Technology Planning Project of Shenzhen,No.JCYJ20230807140559047(to LY)+3 种基金Key-Area Research and Development Program of Guangdong Province,No.2020B0909020004(to GL)Guangdong Basic and Applied Research Foundation,No.2023A1515011478(to LY)the Science and Technology Program of Guangdong Province,No.2022A0505090007(to GL)Ministry of Science and Technology,Shenzhen,No.QN2022032013L(to LY)。
文摘Neural machine interface technology is a pioneering approach that aims to address the complex challenges of neurological dysfunctions and disabilities resulting from conditions such as congenital disorders,traumatic injuries,and neurological diseases.Neural machine interface technology establishes direct connections with the brain or peripheral nervous system to restore impaired motor,sensory,and cognitive functions,significantly improving patients'quality of life.This review analyzes the chronological development and integration of various neural machine interface technologies,including regenerative peripheral nerve interfaces,targeted muscle and sensory reinnervation,agonist–antagonist myoneural interfaces,and brain–machine interfaces.Recent advancements in flexible electronics and bioengineering have led to the development of more biocompatible and highresolution electrodes,which enhance the performance and longevity of neural machine interface technology.However,significant challenges remain,such as signal interference,fibrous tissue encapsulation,and the need for precise anatomical localization and reconstruction.The integration of advanced signal processing algorithms,particularly those utilizing artificial intelligence and machine learning,has the potential to improve the accuracy and reliability of neural signal interpretation,which will make neural machine interface technologies more intuitive and effective.These technologies have broad,impactful clinical applications,ranging from motor restoration and sensory feedback in prosthetics to neurological disorder treatment and neurorehabilitation.This review suggests that multidisciplinary collaboration will play a critical role in advancing neural machine interface technologies by combining insights from biomedical engineering,clinical surgery,and neuroengineering to develop more sophisticated and reliable interfaces.By addressing existing limitations and exploring new technological frontiers,neural machine interface technologies have the potential to revolutionize neuroprosthetics and neurorehabilitation,promising enhanced mobility,independence,and quality of life for individuals with neurological impairments.By leveraging detailed anatomical knowledge and integrating cutting-edge neuroengineering principles,researchers and clinicians can push the boundaries of what is possible and create increasingly sophisticated and long-lasting prosthetic devices that provide sustained benefits for users.
基金supported by the National Natural Science Foundation of China,No.81571211(to FL)the Natural Science Foundation of Shanghai,No.22ZR1476800(to CH)。
文摘Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.
基金supported by the Key Research and Development Project of Hubei Province of China,2022BCA028(to HC)。
文摘“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal cord.Peripheral nerve injury results in movements or sensation impairments,and represents a serious public health problem.Although severed peripheral nerves have been effectively joined and various therapies have been offered,recovery of sensory or motor functions remains limited,and efficacious therapies for complete repair of a nerve injury remain elusive.The emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and function.Mesenchymal stem cells,as large living cells responsive to the environment,secrete various factors and exosomes.The latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins,microRNA,and messenger RNA derived from parent mesenchymal stem cells.Exosomes have pivotal roles in cell-to-cell communication and nervous tissue function,offering solutions to changes associated with cell-based therapies.Despite ongoing investigations,mesenchymal stem cells and mesenchymal stem cell-derived exosome-based therapies are in the exploratory stage.A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical translation.This review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in peripheral nerve injury,exploring the underlying mechanisms.Subsequently,it provides an overview of the current status of mesenchymal stem cell and exosomebased therapies in clinical trials,followed by a comparative analysis of therapies utilizing mesenchymal stem cells and exosomes.Finally,the review addresses the limitations and challenges associated with use of mesenchymal stem cell-derived exosomes,offering potential solutions and guiding future directions.
基金supported by grants from the Natural Science Foundation of Tianjin(General Program),Nos.23JCYBJC01390(to RL),22JCYBJC00220(to XC),and 22JCYBJC00210(to QL).
文摘Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.
基金supported by the National Natural Science Foundation of China,Nos.82271411(to RG),51803072(to WLiu)grants from the Department of Finance of Jilin Province,Nos.2022SCZ25(to RG),2022SCZ10(to WLiu),2021SCZ07(to RG)+2 种基金Jilin Provincial Science and Technology Program,No.YDZJ202201ZYTS038(to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University,No.2022qnpy11(to WLuo)The Project of China-Japan Union Hospital of Jilin University,No.XHQMX20233(to RG)。
文摘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.
基金supported by the National Natural Science Foundation of China,No.82202718the Natural Science Foundation of Beijing,No.L212050the China Postdoctoral Science Foundation,Nos.2019M664007,2021T140793(all to ZL)。
文摘Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.
基金supported by the National Natural Science Foundation of China,No.31870977(to HYS)the National Key Technologies Research and Development Program of China,No.2017YFA0104700(to FD)+2 种基金2022 Jiangsu Funding Program for Excellent Postdoctoral Talent(to MC)Priority Academic Program Development of Jiangsu Higher Education Institutions[PAPD]the Major Project of Basic Science(Natural Science)Research in Higher Education Institutions of Jiangsu Province,No.22KJA180001(to QRH)。
文摘Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.
