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
Objective Peripheral nerve injury leads to various degrees of functional defects.Nerve guidance conduits are considered as a new promising scaffold for peripheral nerve repair.However,conventional single-material nerv...Objective Peripheral nerve injury leads to various degrees of functional defects.Nerve guidance conduits are considered as a new promising scaffold for peripheral nerve repair.However,conventional single-material nerve conduits have shown limited efficacy in protecting cells from posttraumatic inflammation.This study aims to develop a single-process PLGA-based nerve conduit loaded with melatonin to enhance the biological performance of pure PLGA materials by suppressing oxidative stress and inflammatory responses.Methods The PLGA conduit is prepared with dry-jet wet spinning methods.The melatonin is integrated into PLGA conduits directly with the single-step process.Scanning electrical microscope observation,FTIR test,degradation test and drug releasing test were performed to characterize the morphology and physical properties of the nerve conduits.Schwann cells were cultured to test the biocompatibility of the prepared nerve conduits.Oxidative stress was applied on Schwann cell using hydrogen peroxide.Then the protecting effects of the nerve conduits were tested on the hydrogen peroxide-treated cells.SD rat sciatic model was applied to test the conduit in vivo.Results The melatonin is successfully integrated into the nerve conduit with the dry-jet wet spinning method.Cell adhesion and proliferation test of the Schwann cell indicated that the nerve conduits exhibit excellent biocompatibility.While the mitochondrial morphology observation and JC-1 potential detection also showed protecting effects on Mitochondria.The q-PCR analysis showed nerve conduits reduced cellular oxidative stress and inflammatory responses while enhancing cellular proliferation.A marked enhancement on SD rat sciatic nerve regeneration was also observed on melatonin loaded conduits.Conclusions By integrating melatonin into PLGA using the dryjet wet-spinning technique,the conduit is endowed with multiple functional advantages,including antiinflammatory,antioxidant,and neuroprotective properties.This approach is expected to create a favorable microenvironment for nerve tissue regeneration and provide a new perspective for the treatment of peripheral nerve injuries.展开更多
We have previously shown the success of polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries in rats using freshly harvested,viable peripheral nerve allografts that can conduct action potentia...We have previously shown the success of polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries in rats using freshly harvested,viable peripheral nerve allografts that can conduct action potentials.Because clinical application of polyethylene glycol fusion with viable peripheral nerve allografts demands pre-transplant donor tissue storage,we developed a protocol for ex vivo storage of rat sciatic nerves as viable peripheral nerve allografts,preserving many axons for up to 5 days.The current study evaluated the in vivo use of these stored viable peripheral nerve allografts.We hypothesized that stored viable peripheral nerve allografts with viable axons would enable successful in vivo repair of segmental-loss peripheral nerve injuries via polyethylene glycol-fusion.Polyethylene glycol-fused viable peripheral nerve allografts were classified as successful if they produced significantly improved locomotor recovery,as evaluated by the sciatic functional index,within 8 weeks post-repair.Many Sprague-Dawley and Lewis rats with successfully polyethylene glycol-fused viable peripheral nerve allografts had significantly improved sciatic functional index scores beginning at 5 weeks post-operatively.There was no significant difference in the efficiency and extent of successful polyethylene glycol fusion between stored and freshly harvested viable peripheral nerve allografts.In contrast,rats with non-fused negative control viable peripheral nerve allografts showed no recovery by 8 weeks post-operatively.Additional confirmatory outcome measures included in vivo compound action potentials and assessments of axon morphometry.These results suggest that viable peripheral nerve allografts can be stored and later used for successful polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries.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
Peripheral sensory neurons perceive external signals and convey signals to the central nervous system(CNS).Information transmission occurs via often extremely long axons and timely reactions of the animal require a fa...Peripheral sensory neurons perceive external signals and convey signals to the central nervous system(CNS).Information transmission occurs via often extremely long axons and timely reactions of the animal require a fast conductance velocity.This not only depends on axonal diameter and insulation by glial processes,but it requires the structural integrity of the axon.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
AIM:To evaluate the clinical features,diagnosis,treatment,and outcome of peripheral exudative hemorrhagic chorioretinopathy(PEHCR),a variant of polypoidal choroidal vasculopathy(PCV),in a case series of Chinese patien...AIM:To evaluate the clinical features,diagnosis,treatment,and outcome of peripheral exudative hemorrhagic chorioretinopathy(PEHCR),a variant of polypoidal choroidal vasculopathy(PCV),in a case series of Chinese patients.METHODS:This study was retrospectively conducted from September 2018 to March 2025.Clinical examinations included color fundus photography,B-scan ultrasonography,fluorescein angiography(FA),indocyanine green angiography(ICGA),swept-source optical coherence tomography(SS-OCT),and optical coherence tomography angiography(OCTA),and two active or inactive subgroups and misdiagnosed cases were analyzed.RESULTS:Totally 19 patients(21 eyes)with a mean age of 54.3±9.4(range,36–68)y were included,with a majority of women(n=13,68.4%).The mean follow-up period was 13±1.4(range:1–57)mo.Decreased visual acuity was the most frequent initial manifestation(17 eyes,84.2%),and lesions were mainly distributed in the inferotemporal or temporal quadrant(14 eyes,66.7%),with choroidal polyps and branching neovascular networks revealed by OCTA and ICGA.Nine patients had been previously misdiagnosed with choroidal melanoma,and 6 of them had massive vitreous hemorrhage(VH).PEHCR manifested along a spectrum ranging from active or inactive subretinal hemorrhagic forms to chronic fibrotic or atrophic forms.One patient experienced natural regression.Ten eyes received a mean of 4.7±1.1(range:3–7)intravitreal anti-vascular endothelial growth factor(VEGF)injections,two eyes underwent vitrectomy,and six eyes were treated with vitrectomy combined with anti-VEGF therapy.Best-corrected visual acuity(logMAR)in treated eyes(18 eyes)improved to 0.31±0.25 from the baseline of 1.50±0.75(P<0.001).CONCLUSION:PEHCR is a variant of PCV.Chinese patients with PEHCR have a relatively younger age of onset.Anti-VEGF injections and/or vitrectomy are treatment options for lesion regression or dense VH to gain better visual outcomes.展开更多
Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms...Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms are often overlooked.Recent evidence suggests that monocyte phenotypic plasticity plays a central role in PAD development,affecting atherogenesis,plaque progression,ischemia-reperfusion injury,and chronic ischemic remodeling.This narrative review aims to summarize the latest advances(2023-2025)in understanding monocyte diversity,functional states,and their changes throughout different stages of PAD.We discuss both established and emerging biomarkers,such as circulating monocyte subset proportions,functional assays,immune checkpoint expression,and multi-omics signatures,highlighting their potential for prognosis and the challenges in translating them to clinical practice.We also present a stage-specific approach to mapping out potential therapies,linking monocyte phenotypes to molecular targets and possible interventions.Additionally,we address regulatory,economic,and implementation considerations for applying these findings in a clinical setting.The goal of this review is to facilitate the development of targeted immunomodulatory strategies to improve limb and cardiovascular outcomes in PAD by combining mechanistic understanding with therapeutic innovation.展开更多
Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and ...Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and osteoclast activity.However,the majority of research to date has focused on the direct effects of peripheral nerves and their neurotransmitters on bone regeneration.Emerging studies have begun to reveal a more intricate role of nerves in regulating the immune microenvironment,which is crucial for bone regeneration.This review summarizes how nerves influence bone regeneration through modulation of the immune microenvironment.We first discuss the changes in peripheral nerves during the regenerative process.We then describe conduction and paracrine pathways through which nerves affect the osteogenic immune microenvironment,emphasizing nerves,neural factors,and their impacts.Our goal is to deepen the understanding of the nerve-immune axis in bone regeneration.A better grasp of how nerves influence the osteogenic immune microenvironment may lead to new strategies that integrate the nervous,immune,and skeletal systems to promote bone regeneration.展开更多
AIM:To compare the efficacy of goniosynechialysis(GSL)under a microscope alone(GM)and under direct gonioscopy(GG)for chronic angle-closure glaucoma(CACG)coexisted with cataract.METHODS:A prospective,single-center,and ...AIM:To compare the efficacy of goniosynechialysis(GSL)under a microscope alone(GM)and under direct gonioscopy(GG)for chronic angle-closure glaucoma(CACG)coexisted with cataract.METHODS:A prospective,single-center,and randomized controlled trial was conducted.Patients diagnosed as CACG and cataract were randomly allocated into either GM group or GG group.In GM group,the range of peripheral anterior synechiae(PAS)was confirmed through gonio-lens after phacoemulsification with intraocular lens implantation(PEI).PAS was separated only under a microscope.After separating the closed angle of 360°by this method,we used a surgical gonioscope to confirm the PAS range.If any remaining PAS was present,we would separate them with an iris repositor under the direct gonio-lens until angle of 360°was reopened.In GG group,PAS was separated under direct gonioscopy after PEI until angle of 360°was reopened.The range of residual PAS after GSLs was the primary outcome.Intraoperative complications(hyphema),intraocular pressure(IOP)and anti-glaucoma medication usage after operation were the secondary outcomes.RESULTS:Sixty eyes were included,each group comprising 30 eyes.The average age[GM group:66.3±6.8y(12 males),GG group:67.6±8.9y(7 males),P=0.550],the baseline IOP(GM group:29.6±11.5 mm Hg,GG group:32.4±12.2 mm Hg,P=0.366)and the average initial PAS extent(GM group:8.9±2.6h,GG group:9.4±2.5h,P=0.425)were similar in the two groups.In GM group,the PAS range reduced from 8.9±2.6h before operation to 7.2±2.9h after PEI and 3.3±2.2h after GSL.In GG group,the PAS range reduced from 9.4±2.5h before operation to 7.5±2.9h after PEI and 0.1±0.3h after GSL.The PAS after PEI was significantly reduced compared to the preoperative PAS in both groups(all P<0.001).The extent of residual PAS after GSL in GM group was larger than that in GG group with significant statistical difference(P<0.001).Patients who underwent GSL without a gonioscope were more likely to develop hyphema than those who underwent GSL under direct gonioscopy.The difference of hyphema grade between the two groups was statistically significant(P=0.019).CONCLUSION:PEI alone can not open 360°of angle completely.PEI+GSL significantly reduced PAS range.But for patients with CACG,GSL under a microscope alone is more difficult to separate stable PAS completely and adequately than GSL under direct gonioscopy.展开更多
The spinal cord links the brain and the peripheral nervous system and has important sensory and motor functions.Impairments in the spinal cord occur in different diseases,such as spinal cord injury,multiple sclerosis,...The spinal cord links the brain and the peripheral nervous system and has important sensory and motor functions.Impairments in the spinal cord occur in different diseases,such as spinal cord injury,multiple sclerosis,pain,motor neuron diseases,and neurodegenerative diseases.Imaging of the spinal cord has been challenging,partly due to its small size and deep anatomical location.Additionally,in an animal model,motion artifacts further influence the in vivo imaging quality of the spinal cord.Recent advances have pushed boundaries for in vivo imaging in living animals(even behaving animals).展开更多
Peripheral nerve injury is a complex condition presenting significant clinical treatment challenges due to the limited regenerative capacity of peripheral nerves.Nerve conduits have been seen as a promising strategy t...Peripheral nerve injury is a complex condition presenting significant clinical treatment challenges due to the limited regenerative capacity of peripheral nerves.Nerve conduits have been seen as a promising strategy to overcome the shortage of other treatment options(e.g.,nerve graft).However,nerve regeneration occurs within a complex environment,and elaborate modulation is needed to meet repair requirements.The aim of this study was to investigate and explore a multifunctional nerve conduit with reactive oxygen species clearing,immune modulation to reshape the regenerative environment,and topographic cues and electrical signals to guide nerve growth.We developed an electroactive nerve guidance conduit composed of polylactic-glycolic acid and carbon nanotubes with an oriented structure using electrospinning and modified it with mussel-inspired polydopamine combining neurotrophin-3.The resulting nerve scaffold exhibited favorable orientation,electrical conductivity,and mechanical properties.Continuous release of neurotrophin-3 from the nerve conduit supported nerve regeneration throughout the repair process.In vitro assessments confirmed the cytocompatibility,reactive oxygen species scavenging,and immune regulation capabilities of the nerve scaffolds.In a rat sciatic nerve defect model,the nerve scaffolds effectively prevented muscle atrophy and promoted nerve regeneration and functional recovery over a 12-week period.These findings suggest that polydopamine-modified,electroactive,oriented nerve guidance conduits with multiple bioactive functions hold great promise for the repair of peripheral nerve injuries.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
Autologous nerve transplantation is currently recognized as the gold standard for treating seve re peripheral nerve injuries in clinical practice.Howeve r,challenges such as a limited supply of donors,complications in...Autologous nerve transplantation is currently recognized as the gold standard for treating seve re peripheral nerve injuries in clinical practice.Howeve r,challenges such as a limited supply of donors,complications in the donor area,and the formation of neuromas necessitate the optimization of existing transplantation strategies.Additionally,the development of new and promising repair methods is a critical issue in the field of peripheral nerve research.The purpose of this article is to compare the advantages and disadvantages of autologous,allogeneic,decellularized nerve grafts,and cell-composite graft,as well as to summarize the diffe rences in their prognostic factors and associated adve rse events.The length,diamete r,polarity,and sensory or motor origin of autografts all influence axonal regeneration.While pre-denaturation treatment can accele rate early regeneration,long-term functional outcomes of autografts do not show significant differences compared with fresh autologous grafts.For decellularized nerve grafts,defect length is identified as an independent risk factor,and the internal microenvironment(delayed angiogenesis,Schwann cell senescence,and reduced T-cell infiltration)is considered a key factor limiting long-segment regeneration.Additionally,the decellula rization process(whether chemical,physical,or supercritical CO_(2))affects the integrity of the extracellular matrix and the presence of immune residuals,which directly impacts axonal guidance and host integration.Common adve rse events following autograft transplantation include donor site numbness,neuromas,and scarring.In contrast,adverse events associated with decellularized nerve graft transplantation may present as inflammatory reactions,excessive scar prolife ration,and misalignment or reconnection of regenerating axons,which can lead to sensory-m otor cross-innervation.To mitigate these issues,combining decellularized nerve grafts with autologous Schwann cells,mesenchymal stem cells,or induced pluripotent stem cellderived cells may help bridge the gap with autografts.However,the fact that structural recovery does not necessarily lead to functional recovery needs further clarification.Future research should establish la rge animal models to replicate the limits of human regenerative capacity,use gene editing to enhance the phenotype and microenvironment of transplanted cells,and develop a mild combined decellularization process that maximizes the preservation of natural nerve grafts.Through multidimensional optimization,decellularized nerve grafts have the potential to ultimately re place autograft transplantation,enabling precise repair of individualized,long-segment,and complex nerve defects.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
Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages.Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and m...Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages.Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and myelin during Wallerian degeneration,which is a prerequisite for nerve regeneration,we hypothesized that microRNA-301a regulates Wallerian degeneration and nerve regeneration via impacts on Schwann cell migration and phagocytosis.Herein,we found low expression of microRNA-301a in intact sciatic nerves,with no impact of the microRNA-301a knockout on nerve structure and function.By contrast,we found significant upregulation of microRNA-301a in injured sciatic nerves.We established a sciatic nerve crush model in microRNA-301a knockout mice,which exhibited attenua9ted morphological and functional regeneration following sciatic nerve crush injury.The microRNA-301a knockout also led to significantly inhibited Wallerian degeneration in an in vivo sciatic nerve-transection model and in an in vitro nerve explant block model.Schwann cells with the microRNA-301a knockout showed inhibition of phagocytosis and migration,which was reversible under transfection with microRNA-301a mimics.Rescue experiments involving transfection of microRNA-301a-knockout Schwann cells with microRNA-301a mimics or treatment with the C-X-C motif receptor 4 inhibitor WZ811 indicated the mechanistic involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway in the role of microRNA-301a.Combined with our previous findings in macrophages,we conclude that microRNA-301a plays a key role in peripheral nerve injury and repair by regulating the migratory and phagocytic capabilities of Schwann cells and macrophages via the Yin Yang 1/C-X-C motif receptor 4 pathway.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
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.
文摘Objective Peripheral nerve injury leads to various degrees of functional defects.Nerve guidance conduits are considered as a new promising scaffold for peripheral nerve repair.However,conventional single-material nerve conduits have shown limited efficacy in protecting cells from posttraumatic inflammation.This study aims to develop a single-process PLGA-based nerve conduit loaded with melatonin to enhance the biological performance of pure PLGA materials by suppressing oxidative stress and inflammatory responses.Methods The PLGA conduit is prepared with dry-jet wet spinning methods.The melatonin is integrated into PLGA conduits directly with the single-step process.Scanning electrical microscope observation,FTIR test,degradation test and drug releasing test were performed to characterize the morphology and physical properties of the nerve conduits.Schwann cells were cultured to test the biocompatibility of the prepared nerve conduits.Oxidative stress was applied on Schwann cell using hydrogen peroxide.Then the protecting effects of the nerve conduits were tested on the hydrogen peroxide-treated cells.SD rat sciatic model was applied to test the conduit in vivo.Results The melatonin is successfully integrated into the nerve conduit with the dry-jet wet spinning method.Cell adhesion and proliferation test of the Schwann cell indicated that the nerve conduits exhibit excellent biocompatibility.While the mitochondrial morphology observation and JC-1 potential detection also showed protecting effects on Mitochondria.The q-PCR analysis showed nerve conduits reduced cellular oxidative stress and inflammatory responses while enhancing cellular proliferation.A marked enhancement on SD rat sciatic nerve regeneration was also observed on melatonin loaded conduits.Conclusions By integrating melatonin into PLGA using the dryjet wet-spinning technique,the conduit is endowed with multiple functional advantages,including antiinflammatory,antioxidant,and neuroprotective properties.This approach is expected to create a favorable microenvironment for nerve tissue regeneration and provide a new perspective for the treatment of peripheral nerve injuries.
基金National Institutes of Health(NIH)R01-NS128086 grant(to GDB and JSB)Lone Star Paralysis Foundation(to GDB).
文摘We have previously shown the success of polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries in rats using freshly harvested,viable peripheral nerve allografts that can conduct action potentials.Because clinical application of polyethylene glycol fusion with viable peripheral nerve allografts demands pre-transplant donor tissue storage,we developed a protocol for ex vivo storage of rat sciatic nerves as viable peripheral nerve allografts,preserving many axons for up to 5 days.The current study evaluated the in vivo use of these stored viable peripheral nerve allografts.We hypothesized that stored viable peripheral nerve allografts with viable axons would enable successful in vivo repair of segmental-loss peripheral nerve injuries via polyethylene glycol-fusion.Polyethylene glycol-fused viable peripheral nerve allografts were classified as successful if they produced significantly improved locomotor recovery,as evaluated by the sciatic functional index,within 8 weeks post-repair.Many Sprague-Dawley and Lewis rats with successfully polyethylene glycol-fused viable peripheral nerve allografts had significantly improved sciatic functional index scores beginning at 5 weeks post-operatively.There was no significant difference in the efficiency and extent of successful polyethylene glycol fusion between stored and freshly harvested viable peripheral nerve allografts.In contrast,rats with non-fused negative control viable peripheral nerve allografts showed no recovery by 8 weeks post-operatively.Additional confirmatory outcome measures included in vivo compound action potentials and assessments of axon morphometry.These results suggest that viable peripheral nerve allografts can be stored and later used for successful polyethylene glycol fusion repair of segmental-loss peripheral nerve injuries.
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).
基金funded by a grant of the Deutsche Forschungsgemeinschaft(DFG)(SFB 1348,B5)to CK.
文摘Peripheral sensory neurons perceive external signals and convey signals to the central nervous system(CNS).Information transmission occurs via often extremely long axons and timely reactions of the animal require a fast conductance velocity.This not only depends on axonal diameter and insulation by glial processes,but it requires the structural integrity of the axon.
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.
基金Supported by the National Natural Science Foundation of China(No.82220108017,No.82141128)The Capital Health Research and Development of Special(No.2024-1-2052)+1 种基金Science&Technology Project of Beijing Municipal Science&Technology Commission(No.Z201100005520045)Sanming Project of Medicine in Shenzhen(No.SZSM202311018)。
文摘AIM:To evaluate the clinical features,diagnosis,treatment,and outcome of peripheral exudative hemorrhagic chorioretinopathy(PEHCR),a variant of polypoidal choroidal vasculopathy(PCV),in a case series of Chinese patients.METHODS:This study was retrospectively conducted from September 2018 to March 2025.Clinical examinations included color fundus photography,B-scan ultrasonography,fluorescein angiography(FA),indocyanine green angiography(ICGA),swept-source optical coherence tomography(SS-OCT),and optical coherence tomography angiography(OCTA),and two active or inactive subgroups and misdiagnosed cases were analyzed.RESULTS:Totally 19 patients(21 eyes)with a mean age of 54.3±9.4(range,36–68)y were included,with a majority of women(n=13,68.4%).The mean follow-up period was 13±1.4(range:1–57)mo.Decreased visual acuity was the most frequent initial manifestation(17 eyes,84.2%),and lesions were mainly distributed in the inferotemporal or temporal quadrant(14 eyes,66.7%),with choroidal polyps and branching neovascular networks revealed by OCTA and ICGA.Nine patients had been previously misdiagnosed with choroidal melanoma,and 6 of them had massive vitreous hemorrhage(VH).PEHCR manifested along a spectrum ranging from active or inactive subretinal hemorrhagic forms to chronic fibrotic or atrophic forms.One patient experienced natural regression.Ten eyes received a mean of 4.7±1.1(range:3–7)intravitreal anti-vascular endothelial growth factor(VEGF)injections,two eyes underwent vitrectomy,and six eyes were treated with vitrectomy combined with anti-VEGF therapy.Best-corrected visual acuity(logMAR)in treated eyes(18 eyes)improved to 0.31±0.25 from the baseline of 1.50±0.75(P<0.001).CONCLUSION:PEHCR is a variant of PCV.Chinese patients with PEHCR have a relatively younger age of onset.Anti-VEGF injections and/or vitrectomy are treatment options for lesion regression or dense VH to gain better visual outcomes.
文摘Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms are often overlooked.Recent evidence suggests that monocyte phenotypic plasticity plays a central role in PAD development,affecting atherogenesis,plaque progression,ischemia-reperfusion injury,and chronic ischemic remodeling.This narrative review aims to summarize the latest advances(2023-2025)in understanding monocyte diversity,functional states,and their changes throughout different stages of PAD.We discuss both established and emerging biomarkers,such as circulating monocyte subset proportions,functional assays,immune checkpoint expression,and multi-omics signatures,highlighting their potential for prognosis and the challenges in translating them to clinical practice.We also present a stage-specific approach to mapping out potential therapies,linking monocyte phenotypes to molecular targets and possible interventions.Additionally,we address regulatory,economic,and implementation considerations for applying these findings in a clinical setting.The goal of this review is to facilitate the development of targeted immunomodulatory strategies to improve limb and cardiovascular outcomes in PAD by combining mechanistic understanding with therapeutic innovation.
基金supported by grants from the National Natural Science Foundation of China(No.82372382,82002333,32371412,and 32071349)the Central Guidance on Local Science and Technology Development Fund of Zhejiang Province(No.2024ZY01033)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(No.LY24C100001)the Key Research and Development Program of Zhejiang(No.2022C01076).
文摘Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and osteoclast activity.However,the majority of research to date has focused on the direct effects of peripheral nerves and their neurotransmitters on bone regeneration.Emerging studies have begun to reveal a more intricate role of nerves in regulating the immune microenvironment,which is crucial for bone regeneration.This review summarizes how nerves influence bone regeneration through modulation of the immune microenvironment.We first discuss the changes in peripheral nerves during the regenerative process.We then describe conduction and paracrine pathways through which nerves affect the osteogenic immune microenvironment,emphasizing nerves,neural factors,and their impacts.Our goal is to deepen the understanding of the nerve-immune axis in bone regeneration.A better grasp of how nerves influence the osteogenic immune microenvironment may lead to new strategies that integrate the nervous,immune,and skeletal systems to promote bone regeneration.
基金Supported by the Program for Zhejiang Leading Talent of S&T Innovation(No.2021R52012)Key Research and Development Projects of Zhejiang Province(No.2022C03112).
文摘AIM:To compare the efficacy of goniosynechialysis(GSL)under a microscope alone(GM)and under direct gonioscopy(GG)for chronic angle-closure glaucoma(CACG)coexisted with cataract.METHODS:A prospective,single-center,and randomized controlled trial was conducted.Patients diagnosed as CACG and cataract were randomly allocated into either GM group or GG group.In GM group,the range of peripheral anterior synechiae(PAS)was confirmed through gonio-lens after phacoemulsification with intraocular lens implantation(PEI).PAS was separated only under a microscope.After separating the closed angle of 360°by this method,we used a surgical gonioscope to confirm the PAS range.If any remaining PAS was present,we would separate them with an iris repositor under the direct gonio-lens until angle of 360°was reopened.In GG group,PAS was separated under direct gonioscopy after PEI until angle of 360°was reopened.The range of residual PAS after GSLs was the primary outcome.Intraoperative complications(hyphema),intraocular pressure(IOP)and anti-glaucoma medication usage after operation were the secondary outcomes.RESULTS:Sixty eyes were included,each group comprising 30 eyes.The average age[GM group:66.3±6.8y(12 males),GG group:67.6±8.9y(7 males),P=0.550],the baseline IOP(GM group:29.6±11.5 mm Hg,GG group:32.4±12.2 mm Hg,P=0.366)and the average initial PAS extent(GM group:8.9±2.6h,GG group:9.4±2.5h,P=0.425)were similar in the two groups.In GM group,the PAS range reduced from 8.9±2.6h before operation to 7.2±2.9h after PEI and 3.3±2.2h after GSL.In GG group,the PAS range reduced from 9.4±2.5h before operation to 7.5±2.9h after PEI and 0.1±0.3h after GSL.The PAS after PEI was significantly reduced compared to the preoperative PAS in both groups(all P<0.001).The extent of residual PAS after GSL in GM group was larger than that in GG group with significant statistical difference(P<0.001).Patients who underwent GSL without a gonioscope were more likely to develop hyphema than those who underwent GSL under direct gonioscopy.The difference of hyphema grade between the two groups was statistically significant(P=0.019).CONCLUSION:PEI alone can not open 360°of angle completely.PEI+GSL significantly reduced PAS range.But for patients with CACG,GSL under a microscope alone is more difficult to separate stable PAS completely and adequately than GSL under direct gonioscopy.
文摘The spinal cord links the brain and the peripheral nervous system and has important sensory and motor functions.Impairments in the spinal cord occur in different diseases,such as spinal cord injury,multiple sclerosis,pain,motor neuron diseases,and neurodegenerative diseases.Imaging of the spinal cord has been challenging,partly due to its small size and deep anatomical location.Additionally,in an animal model,motion artifacts further influence the in vivo imaging quality of the spinal cord.Recent advances have pushed boundaries for in vivo imaging in living animals(even behaving animals).
基金supported by the National Key R&D Program of China,No.2022YFC3006200(to YW)the Natural Science Foundation of Beijing,No.7232190(to YW)+1 种基金Zhejiang Province Medical and Health Technology Plan Project,Nos.2022020506(to XW),2024KY1612(to JX),2024KY1615(to MY)Ningbo Clinical Research Center for Orthopedics and Sports Rehabilitation,No.2024L004(to XW).
文摘Peripheral nerve injury is a complex condition presenting significant clinical treatment challenges due to the limited regenerative capacity of peripheral nerves.Nerve conduits have been seen as a promising strategy to overcome the shortage of other treatment options(e.g.,nerve graft).However,nerve regeneration occurs within a complex environment,and elaborate modulation is needed to meet repair requirements.The aim of this study was to investigate and explore a multifunctional nerve conduit with reactive oxygen species clearing,immune modulation to reshape the regenerative environment,and topographic cues and electrical signals to guide nerve growth.We developed an electroactive nerve guidance conduit composed of polylactic-glycolic acid and carbon nanotubes with an oriented structure using electrospinning and modified it with mussel-inspired polydopamine combining neurotrophin-3.The resulting nerve scaffold exhibited favorable orientation,electrical conductivity,and mechanical properties.Continuous release of neurotrophin-3 from the nerve conduit supported nerve regeneration throughout the repair process.In vitro assessments confirmed the cytocompatibility,reactive oxygen species scavenging,and immune regulation capabilities of the nerve scaffolds.In a rat sciatic nerve defect model,the nerve scaffolds effectively prevented muscle atrophy and promoted nerve regeneration and functional recovery over a 12-week period.These findings suggest that polydopamine-modified,electroactive,oriented nerve guidance conduits with multiple bioactive functions hold great promise for the repair of peripheral nerve injuries.
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National Natural Science Foundation of China,No.82471412Science&Technology Innovation Talents Project of Henan Educational Committee,No.25HASTIT059+2 种基金Henan Academy of Medical Sciences Clinical Scientist Program,No.S20240069Young and Middle-aged Health Science and Technology Innovation Talent of Henan Province,No.JQRC2024014Henan Provincial Science&Technology Research and Development Program Joint Fund,No.232301420063(all to NZ)。
文摘Autologous nerve transplantation is currently recognized as the gold standard for treating seve re peripheral nerve injuries in clinical practice.Howeve r,challenges such as a limited supply of donors,complications in the donor area,and the formation of neuromas necessitate the optimization of existing transplantation strategies.Additionally,the development of new and promising repair methods is a critical issue in the field of peripheral nerve research.The purpose of this article is to compare the advantages and disadvantages of autologous,allogeneic,decellularized nerve grafts,and cell-composite graft,as well as to summarize the diffe rences in their prognostic factors and associated adve rse events.The length,diamete r,polarity,and sensory or motor origin of autografts all influence axonal regeneration.While pre-denaturation treatment can accele rate early regeneration,long-term functional outcomes of autografts do not show significant differences compared with fresh autologous grafts.For decellularized nerve grafts,defect length is identified as an independent risk factor,and the internal microenvironment(delayed angiogenesis,Schwann cell senescence,and reduced T-cell infiltration)is considered a key factor limiting long-segment regeneration.Additionally,the decellula rization process(whether chemical,physical,or supercritical CO_(2))affects the integrity of the extracellular matrix and the presence of immune residuals,which directly impacts axonal guidance and host integration.Common adve rse events following autograft transplantation include donor site numbness,neuromas,and scarring.In contrast,adverse events associated with decellularized nerve graft transplantation may present as inflammatory reactions,excessive scar prolife ration,and misalignment or reconnection of regenerating axons,which can lead to sensory-m otor cross-innervation.To mitigate these issues,combining decellularized nerve grafts with autologous Schwann cells,mesenchymal stem cells,or induced pluripotent stem cellderived cells may help bridge the gap with autografts.However,the fact that structural recovery does not necessarily lead to functional recovery needs further clarification.Future research should establish la rge animal models to replicate the limits of human regenerative capacity,use gene editing to enhance the phenotype and microenvironment of transplanted cells,and develop a mild combined decellularization process that maximizes the preservation of natural nerve grafts.Through multidimensional optimization,decellularized nerve grafts have the potential to ultimately re place autograft transplantation,enabling precise repair of individualized,long-segment,and complex nerve defects.
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.
基金supported by the National Natural Science Foundation of China,No.82071386(to JG).
文摘Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages.Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and myelin during Wallerian degeneration,which is a prerequisite for nerve regeneration,we hypothesized that microRNA-301a regulates Wallerian degeneration and nerve regeneration via impacts on Schwann cell migration and phagocytosis.Herein,we found low expression of microRNA-301a in intact sciatic nerves,with no impact of the microRNA-301a knockout on nerve structure and function.By contrast,we found significant upregulation of microRNA-301a in injured sciatic nerves.We established a sciatic nerve crush model in microRNA-301a knockout mice,which exhibited attenua9ted morphological and functional regeneration following sciatic nerve crush injury.The microRNA-301a knockout also led to significantly inhibited Wallerian degeneration in an in vivo sciatic nerve-transection model and in an in vitro nerve explant block model.Schwann cells with the microRNA-301a knockout showed inhibition of phagocytosis and migration,which was reversible under transfection with microRNA-301a mimics.Rescue experiments involving transfection of microRNA-301a-knockout Schwann cells with microRNA-301a mimics or treatment with the C-X-C motif receptor 4 inhibitor WZ811 indicated the mechanistic involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway in the role of microRNA-301a.Combined with our previous findings in macrophages,we conclude that microRNA-301a plays a key role in peripheral nerve injury and repair by regulating the migratory and phagocytic capabilities of Schwann cells and macrophages via the Yin Yang 1/C-X-C motif receptor 4 pathway.
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.
