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
FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways ...FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.展开更多
Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies a...Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies available to promote nerve regeneration.Tacrolimus accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery.The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure.Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days.Size and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible byproducts.Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic delivery.Given its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.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
Pericytes are multifunctional mural cells that surround the abluminal wall of endothelial cells and are associated with vascular development,vascular permeability,and angiogenesis.Additionally,pericytes demonstrate st...Pericytes are multifunctional mural cells that surround the abluminal wall of endothelial cells and are associated with vascular development,vascular permeability,and angiogenesis.Additionally,pericytes demonstrate stem cell-like properties and contribute to neuroinflammatory processes.Pericytes have been extensively studied in the central nervous system.However,specific mechanisms underlying its involvement in various physiological and pathological conditions,especially in erectile dysfunction(ED),remain poorly understood.Advancements in in vitro and in vitro techniques,such as single-cell RNA sequencing,are expanding our understanding of pericytes.Recent studies have shown that pericyte dysfunction is considered an important factor in the pathogenesis of vascular and neurological ED.Therefore,this study aims to analyze the specific role of pericytes in ED,focusing on diabetic and neurogenic ED.This article provides a comprehensive review of research findings on PubMed from 2000 to 2023,concerning pericyte dysfunction in the process of ED,offering valuable insights,and suggesting directions for further research.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
Background: Peripheral nerve regeneration is a critical research area with significant implications for neurology,neurosurgery,and regenerative medicine.A bibliometric analysis was conducted to provide a structured ov...Background: Peripheral nerve regeneration is a critical research area with significant implications for neurology,neurosurgery,and regenerative medicine.A bibliometric analysis was conducted to provide a structured overview of research trends,intellectual impact,and evolving themes in peripheral nerve regeneration.This study aimed to identify the most influential research articles on peripheral nerve regeneration;analyze keyword trends,thematic evolution,and co-word structures;assess the contributions of top authors,universities,and countries;and examine collaboration networks and research dynamics.Methods: A systematic bibliometric approach was employed using two search strategies.The first strategy involved searching within the title,abstract,and keyword fields,yielding 15 317 papers,whereas the second strategy was restricted to searching titles only,retrieving 3 531 papers.From these,the 100 most cited papers were selected for analysis.A thematic analysis was conducted using co-word clustering.The leading contributors were ranked according to the number of publications,citations,h-index,g-index,and m-index.Results: The bibliometric analysis provided several key insights.Keyword analysis using bi-and tri-gram techniques revealed the dominant research themes within the field.The top contributors,including authors,universities,and countries,were ranked based on their productivity and citation impact.Collaboration networks were mapped at the author,institutional,and country levels,highlighting key partnerships and global research interactions.Thematic analysis classified research into seven major domains: neural regeneration and repair;cellular and molecular biology;biomaterials and tissue engineering;experimental studies and statistical analyses;functional and therapeutic aspects;neuropathic pain and peripheral nerve disorders;and Schwann cell and cellular responses.Additionally,the ten most influential papers were reviewed in detail to understand their contributions to the field.Conclusion: This study provides a comprehensive and structured overview of peripheral nerve regeneration research.These findings offer valuable insights into the intellectual foundation of the field by identifying key contributors,research trends,and collaboration patterns.The results serve as a guide for future research,helping researchers to navigate the evolving landscape of peripheral nerve regeneration.展开更多
Nerve guidance conduits(NGCs)effectively support and guide the regeneration of injured nerves.However,traditional NGCs often lack essential growth factors and fail to create a biomimetic microenvironment conducive to ...Nerve guidance conduits(NGCs)effectively support and guide the regeneration of injured nerves.However,traditional NGCs often lack essential growth factors and fail to create a biomimetic microenvironment conducive to nerve regrowth.This study develops a highly bionic nerve guidance conduit(HB-NGC)using hybrid high-voltage electrotechnologies that integrate electrospinning with electrohydrodynamic(EHD)printing.The outer layer consists of electrospun polycaprolactone fibers loaded with carboxyl-multi-walled carbon nanotubes,while the inner layer is composed of highly aligned polycaprolactone fibers created by EHD printing.The tubular core of the HB-NGC is filled with hyaluronic acid methacryloyl(HAMA)hydrogel encapsulating bone marrow mesenchymal stem cells(BMSCs).This highly biomimetic NGC is conductive,capable of guiding axon growth,and sustainably releases growth factors,effectively mimicking the structure,function,and characteristics of natural peripheral nerves.Its distinctive architectural layers provide an exceptional bionic microenvironment by restoring physical pathways,facilitating electrical signal conduction,and supplying an extracellular matrix(ECM)environment enriched with essential growth factors.Additionally,the HB-NGC’s morphology,along with its physicochemical and mechanical properties,effectively bridges the gap between severed nerve ends.In vivo animal studies validate the HB-NGC’s effectiveness,highlighting its significant potential to enhance peripheral nerve regeneration.展开更多
Objective To observe the effects of moxibustion at Huantiao(GB30)acupoint on nerve repair,regeneration,and function in rats with sciatic nerve injury(SNI),and explore the possible mechanism of SNI improvement via moxi...Objective To observe the effects of moxibustion at Huantiao(GB30)acupoint on nerve repair,regeneration,and function in rats with sciatic nerve injury(SNI),and explore the possible mechanism of SNI improvement via moxibustion.Methods A total of 70 specific pathogen-free(SPF)grade male Sprague-Dawley(SD)rats were randomly assigned to control group(n=10)and model group(n=60).Following replication of SNI to model group rats,60 SNI model rats were randomly allocated to SNI groups of 1 d,3 d,and 7 d and moxibustion groups of 1 d,3 d,and 7 d with 10 rats in each group.Moxibustion groups were given moxibustion at the Huantiao(GB30)acupoint on the affected side with a 5 cm distance from the skin under isoflurane respiratory anesthesia and treated once a day for 20 min for 1 d,3 d,and 7 d,respectively.Control and SNI groups were anesthetized with isoflurane daily for 20 min.Open field tests and thermal pain threshold tests were conducted,and the general condition of rats was observed in each group pre-modeling and on treatment day 1,3,and 7.At the end of the treatment,immunofluorescence was used to detect the axonal growth rate,axonal growth density,and Schwann cells(SCs)proliferation in the middle 1-mm cross-section of the crush injury segment in rats.The gastrocnemius muscles on both sides of the rats were taken and weighed to calculate the wet weight ratio of the gastrocnemius muscles on both sides to observe the muscle atrophy of the rats,and hematoxylin-eosin(HE)staining was used to observe the pathomorphological changes of the gastrocnemius muscles on the affected side.Quantitative real-time polymerase chain reaction(qPCR)was used to detect the expression levels of nerve growth factor(NGF),interferon(IFN),macrophage migration inhibitory factor(MIF),interleukin(IL)-4,and transforming growth factor(TGF)-βin the sciatic nerve tissue of the rats.Results After modeling,rats in both moxibustion and SNI groups showed typical signs of pain behaviors(bending and curling of the hind soles of the affected side,licking claws,and lameness)and decreased activity compared with control group.The main benefits of moxibustion were evident from day 3:compared with SNI group,rats in moxibustion group had marked relief of pain behavior,increased activity levels and movement,and a lower response to thermal pain.At the same time,moxibustion significantly promoted the repair of SNI,as evidenced by the significantly better axonal growth rate,growth density,and SCs proliferation density in the crush injury segment compared with SNI group(P<0.01).Moxibustion also regulated the local microenvironment of the injury,up-regulated the pro-nerve repair factors NGF,IL-4,and TGF-β(P<0.05),and down-regulated the pro-inflammatory factors IFN-γ(P<0.01)and MIF(P<0.05).By day 7,the histomorphology of the gastrocnemius muscle in moxibustion group was improved,as indicated by enlarged muscle fibers,elevated regular myocyte morphology and wet weight ratio of the affected and unaffected sides(P<0.05),as well as a sustained high expression levels of NGF,IL-4,and TGF-β(P<0.05,P<0.05,and P<0.01,respectively),and a maintenance of low level of IFN-γ(P<0.01).Concurrently,the MIF level was not significantly different from SNI group(P>0.05).Conclusion Moxibustion at the Huantiao(GB30)acupoint effectively improves motor function and promotes recovery of sensory function and nerve regeneration in SNI rats,which may be related to the regulation of local inflammatory response,the promotion of nerve growth factor expression,the improvement of regenerative microenvironment,and the acceleration of SCs proliferation and axonal growth rate in damaged nerves.展开更多
Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and foun...Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.展开更多
Retinal ganglion cells(RGCs)extend through the optic nerve,connecting with neurons in visually related nuclei.Similar to most mature neurons in the central nervous system,once damaged,RGCs are unable to regenerate the...Retinal ganglion cells(RGCs)extend through the optic nerve,connecting with neurons in visually related nuclei.Similar to most mature neurons in the central nervous system,once damaged,RGCs are unable to regenerate their axons and swiftly progress to cell death.In addition to cell-intrinsic mechanisms,extrinsic factors within the extracellular environment,notably glial and inflammatory cells,exert a pivotal role in modulating RGC neurodegeneration and regeneration.Moreover,burgeoning evidence suggests that retinal interneurons,specifically amacrine cells,exert a substantial influence on RGC survival and axon regeneration.In this review,we consolidate the present understanding of extrinsic factors implicated in RGC survival and axon regeneration,and deliberate on potential therapeutic strategies aimed at fostering optic nerve regeneration and restoring vision.展开更多
Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to...Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells.However,axon regeneration and repair do not automatically result in the restoration of function,which is the ultimate therapeutic goal but also a major clinical challenge.Transforming growth factor(TGF)is a multifunctional cytokine that regulates various biological processes including tissue repair,embryo development,and cell growth and differentiation.There is accumulating evidence that TGF-βfamily proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells;recruiting specific immune cells;controlling the permeability of the blood-nerve barrier,thereby stimulating axon growth;and inhibiting remyelination of regenerated axons.TGF-βhas been applied to the treatment of peripheral nerve injury in animal models.In this context,we review the functions of TGF-βin peripheral nerve regeneration and potential clinical applications.展开更多
We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To ide...We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We obtained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function restoration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP.展开更多
Exogenous discharge can positively promote nerve repair. We, therefore, hypothesized that endogenous discharges may have similar effects. The phrenic nerve and intercostal nerve, controlled by the respiratory center, ...Exogenous discharge can positively promote nerve repair. We, therefore, hypothesized that endogenous discharges may have similar effects. The phrenic nerve and intercostal nerve, controlled by the respiratory center, can emit regular nerve impulses; therefore these endogenous automatically discharging nerves might promote nerve regeneration. Action potential discharge patterns were examined in the diaphragm, external intercostal and latissimus dorsi muscles of rats. The phrenic and intercostal nerves showed rhythmic clusters of discharge, which were consistent with breathing frequency. From the first to the third intercostal nerves, spontaneous discharge amplitude was gradually increased. There was no obvious rhythmic discharge in the thoracodorsal nerve. Four animal groups were performed in rats as the musculocutaneous nerve cut and repaired was bland control. The other three groups were followed by a side-to-side anastomosis with the phrenic nerve, intercostal nerve and thoracodorsal nerve. Compound muscle action potentials in the biceps muscle innervated by the musculocutaneous nerve were recorded with electrodes. The tetanic forces of ipsilateral and contralateral biceps muscles were detected by a force displacement transducer. Wet muscle weight recovery rate was measured and pathological changes were observed using hematoxylin-eosin staining. The number of nerve fibers was observed using toluidine blue staining and changes in nerve ultrastructure were observed using transmission electron microscopy. The compound muscle action potential amplitude was significantly higher at 1 month after surgery in phrenic and intercostal nerve groups compared with the thoracodorsal nerve and blank control groups. The recovery rate of tetanic tension and wet weight of the right biceps were significantly lower at 2 months after surgery in the phrenic nerve, intercostal nerve, and thoracodorsal nerve groups compared with the negative control group. The number of myelinated axons distal to the coaptation site of the musculocutaneous nerve at 1 month after surgery was significantly higher in phrenic and intercostal nerve groups than in thoracodorsal nerve and negative control groups. These results indicate that endogenous autonomic discharge from phrenic and intercostal nerves can promote nerve regeneration in early stages after brachial plexus injury.展开更多
Olfactory ensheathing cells(OECs)are promising seed cells for nerve regeneration.However,their application is limited by the hypoxic environment usually present at the site of injury.Exosomes derived from human umbili...Olfactory ensheathing cells(OECs)are promising seed cells for nerve regeneration.However,their application is limited by the hypoxic environment usually present at the site of injury.Exosomes derived from human umbilical cord mesenchymal stem cells have the potential to regulate the pathological processes that occur in response to hypoxia.The ability of OECs to migrate is unknown,especially in hypoxic conditions,and the effect of OECs combined with exosomes on peripheral nerve repair is not clear.Better understanding of these issues will enable the potential of OECs for the treatment of nerve injury to be addressed.In this study,OECs were acquired from the olfactory bulb of Sprague Dawley rats.Human umbilical cord mesenchymal stem cell-derived exosomes(0–400μg/mL)were cultured with OECs for 12–48 hours.After culture with 400μg/mL exosomes for 24 hours,the viability and proliferation of OECs were significantly increased.We observed changes to OECs subjected to hypoxia for 24 hours and treatment with exosomes.Exosomes significantly promoted the survival and migration of OECs in hypoxic conditions,and effectively increased brain-derived neurotrophic factor gene expression,protein levels and secretion.Finally,using a 12 mm left sciatic nerve defect rat model,we confirmed that OECs and exosomes can synergistically promote motor and sensory function of the injured sciatic nerve.These findings show that application of OECs and exosomes can promote nerve regeneration and functional recovery.This study was approved by the Institutional Ethical Committee of the Air Force Medical University,China(approval No.IACUC-20181004)on October 7,2018;and collection and use of human umbilical cord specimens was approved by the Ethics Committee of the Linyi People’s Hospital,China(approval No.30054)on May 20,2019.展开更多
Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord inj...Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen＇s method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord.展开更多
The cornea has unique features that make it a useful model for regenerative medicine studies. It is an avascular, transparent, densely innervated tissue and any pathological changes can be easily detected by slit lamp...The cornea has unique features that make it a useful model for regenerative medicine studies. It is an avascular, transparent, densely innervated tissue and any pathological changes can be easily detected by slit lamp examination. Corneal sensitivity is provided by the ophthalmic branch of the trigeminal nerve that elicits protective reflexes such as blinking and tearing and exerts trophic support by releasing neuromediators and growth factors. Corneal nerves are easily evaluated for both function and morphology using standard instruments such as corneal esthesiometer and in vivo confocal microscope. All local and systemic conditions that are associated with damage of the trigeminal nerve cause the development of neurotrophic keratitis, a rare degenerative disease. Neurotrophic keratitis is characterized by impairment of corneal sensitivity associated with development of persistent epithelial defects that may progress to corneal ulcer, melting and perforation. Current neurotrophic keratitis treatments aim at supporting corneal healing and preventing progression of corneal damage. Novel compounds able to stimulate corneal nerve recovery are in advanced development stage. Among them, nerve growth factor eye drops showed to be safe and effective in stimulating corneal healing and improving corneal sensitivity in patients with neurotrophic keratitis. Neurotrophic keratitis represents an useful model to evaluate in clinical practice novel neuro-regenerative drugs.展开更多
Studies have confirmed that bone marrow-derived mesenchymal stem cells （MSCs） can be used for treatment of several nervous system diseases. However, isolation of bone marrow-derived MSCs （BMSCs） is an invasive and...Studies have confirmed that bone marrow-derived mesenchymal stem cells （MSCs） can be used for treatment of several nervous system diseases. However, isolation of bone marrow-derived MSCs （BMSCs） is an invasive and painful process and the yield is very low. Therefore, there is a need to search for other alterative stem cell sources. Adipose-derived MSCs （ADSCs） have phenotypic and gene expression profiles similar to those of BMSCs. The production of ADSCs is greater than that of BMSCs, and ADSCs proliferate faster than BMSCs. To compare the effects of venous grafts containing BMSCs or ADSCs on sciatic nerve injury, in this study, rats were randomly divided into four groups： sham （only sciatic nerve exposed）, Matrigel （MG; sciatic nerve injury ＋ intravenous transplantation of MG vehicle）, ADSCs （sciatic nerve injury ＋ intravenous MG containing ADSCs）, and BMSCs （sciatic nerve injury ＋ intravenous MG containing BMSCs） groups. Sciatic functional index was calculated to evaluate the function of injured sciatic nerve. Morphologic characteristics of nerves distal to the lesion were observed by toluidine blue staining. Spinal motor neurons labeled with Fluoro-Gold were quantitatively assessed. Compared with sham-operated rats, sciatic functional index was lower, the density of small-diameter fibers was significantly increased, and the number of motor neurons significantly decreased in rats with sciatic nerve injury. Neither ADSCs nor BMSCs significantly improved the sciatic nerve function of rats with sciatic nerve injury,increased fiber density, fiber diameters, axonal diameters, myelin sheath thickness, and G ratios （axonal diameter/fiber diameter ratios） in the sciatic nerve distal to the lesion site. There was no significant difference in the number of spinal motor neurons among ADSCs, BMSCs and MG groups. These results suggest that neither BMSCs nor ADSCs provide satisfactory results for peripheral nerve repair when using MG as the conductor for engraftment.展开更多
BACKGROUND： Mesenchymal stem cells （MSCs） appear to be a good alternative to Schwann cells in the treatment of peripheral nerve injury. Fetal stem cells, like umbilical cord blood （UCB） and umbilical cord （UC） ...BACKGROUND： Mesenchymal stem cells （MSCs） appear to be a good alternative to Schwann cells in the treatment of peripheral nerve injury. Fetal stem cells, like umbilical cord blood （UCB） and umbilical cord （UC） stem cells, have several advantages over adult stem cells. OBJECTIVE： To assess the effects of UC-derived MSCs （UCMSCs） and UCB-derived MSCs （UCBMSCs） in repair of sciatic nerve defects. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at the laboratory of Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, from July to December 2009. MATERIALS： UCMSCs were provided by the Research Institute of Biotechnology, Dongguk University. UCBMSCs were provided by the Laboratory of Stem Cells and Tumor Biology, College of Veterinary Medicine, Seoul National University. Dulbecco＇s modified Eagle＇s medium （DMEM） was purchased from Gibco-BRL, USA. METHODS： Seven-week-old Sprague-Dawley rats were randomly and evenly divided into three groups： DMEM, UCBMSCs, and UCMSCs. A 10-mm defect in the left sciatic nerve was constructed in all rats. DMEM （15 μL） containing 1×10^6 UCBMSCs or UCMSCs was injected into the gap between nerve stumps, with the surrounding epineurium as a natural conduit. For the DMEM group, simple DMEM was injected. MAIN OUTCOME MEASURES： At 7 weeks after sciatic nerve dissection, dorsal root ganglia neurons were labeled by fluorogold retrograde labeling. At 8 weeks, electrophysiology and histomorphometry were performed. At 2, 4, 6, and 8 weeks after surgery, sciatic nerve function was evaluated using gait analysis. RESULTS： The UCBMSCs group and the UCMSCs group exhibited similar sciatic nerve function and electrophysiological indices, which were better than the DMEM group, as measured by gait analysis （P 〈 0.05）. Fluorogold retrograde labeling of sciatic nerve revealed that the UCBMSCs group demonstrated a higher number of labeled neurons; however, the differences were not significant. Histomorphometric indices were similar in the UCBMSCs and UCMSCs groups, and total axon counts, particularly axon density （P 〈 0.05）, were significantly greater in the UCBMSCs and UCMSCs groups than in the DMEM group. CONCLUSION： Transplanting either UCBMSCs or UCMSCs into axotomized sciatic nerves could accelerate and promote sciatic nerve regeneration over 8 weeks. Both treatments had similar effects on nerve regeneration.展开更多
Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the ther- apeutic effects of local admini...Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the ther- apeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly（lactic-co-glycolic acid） biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local ap- plication of icariin after spinal injury can promote peripheral nerve regeneration.展开更多
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.81971177(to YK)the Natural Science Foundation of Beijing,No.7222198(to NH)the Peking University People's Hospital Research and Development Fund,No.RDX2021-01(to YK)。
文摘FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.
基金supported by the German Research Foundation(DA 2255/1-1to SCD)+4 种基金a SickKids Research Training Competition(RESTRACOMP)Graduate Scholarship(to KJWS)an Ontario Graduate Scholarship(to KJWS)a grant from Natural Sciences and Engineering Research Council of Canada(NSERC)(to KJWS)a Kickstarter grant from the Institute of Biomedical Engineering(BME)at the University of Toronto(to KJWS)the Abe Frank Fund from the Riley’s Children Foundation(GHB)。
文摘Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies available to promote nerve regeneration.Tacrolimus accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery.The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure.Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days.Size and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible byproducts.Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic delivery.Given its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.
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 Inha University Research Grant(to JKR).
文摘Pericytes are multifunctional mural cells that surround the abluminal wall of endothelial cells and are associated with vascular development,vascular permeability,and angiogenesis.Additionally,pericytes demonstrate stem cell-like properties and contribute to neuroinflammatory processes.Pericytes have been extensively studied in the central nervous system.However,specific mechanisms underlying its involvement in various physiological and pathological conditions,especially in erectile dysfunction(ED),remain poorly understood.Advancements in in vitro and in vitro techniques,such as single-cell RNA sequencing,are expanding our understanding of pericytes.Recent studies have shown that pericyte dysfunction is considered an important factor in the pathogenesis of vascular and neurological ED.Therefore,this study aims to analyze the specific role of pericytes in ED,focusing on diabetic and neurogenic ED.This article provides a comprehensive review of research findings on PubMed from 2000 to 2023,concerning pericyte dysfunction in the process of ED,offering valuable insights,and suggesting directions for further research.
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Background: Peripheral nerve regeneration is a critical research area with significant implications for neurology,neurosurgery,and regenerative medicine.A bibliometric analysis was conducted to provide a structured overview of research trends,intellectual impact,and evolving themes in peripheral nerve regeneration.This study aimed to identify the most influential research articles on peripheral nerve regeneration;analyze keyword trends,thematic evolution,and co-word structures;assess the contributions of top authors,universities,and countries;and examine collaboration networks and research dynamics.Methods: A systematic bibliometric approach was employed using two search strategies.The first strategy involved searching within the title,abstract,and keyword fields,yielding 15 317 papers,whereas the second strategy was restricted to searching titles only,retrieving 3 531 papers.From these,the 100 most cited papers were selected for analysis.A thematic analysis was conducted using co-word clustering.The leading contributors were ranked according to the number of publications,citations,h-index,g-index,and m-index.Results: The bibliometric analysis provided several key insights.Keyword analysis using bi-and tri-gram techniques revealed the dominant research themes within the field.The top contributors,including authors,universities,and countries,were ranked based on their productivity and citation impact.Collaboration networks were mapped at the author,institutional,and country levels,highlighting key partnerships and global research interactions.Thematic analysis classified research into seven major domains: neural regeneration and repair;cellular and molecular biology;biomaterials and tissue engineering;experimental studies and statistical analyses;functional and therapeutic aspects;neuropathic pain and peripheral nerve disorders;and Schwann cell and cellular responses.Additionally,the ten most influential papers were reviewed in detail to understand their contributions to the field.Conclusion: This study provides a comprehensive and structured overview of peripheral nerve regeneration research.These findings offer valuable insights into the intellectual foundation of the field by identifying key contributors,research trends,and collaboration patterns.The results serve as a guide for future research,helping researchers to navigate the evolving landscape of peripheral nerve regeneration.
基金supported by the Natural Science Foundation of Hebei Province of China(Nos.H2020202002 and H2023202001)the Natural Science Foundation of Tianjin City of China(No.24JCQNJC01180)Science Research Project of Hebei Educational Department(No.BJK2023034).
文摘Nerve guidance conduits(NGCs)effectively support and guide the regeneration of injured nerves.However,traditional NGCs often lack essential growth factors and fail to create a biomimetic microenvironment conducive to nerve regrowth.This study develops a highly bionic nerve guidance conduit(HB-NGC)using hybrid high-voltage electrotechnologies that integrate electrospinning with electrohydrodynamic(EHD)printing.The outer layer consists of electrospun polycaprolactone fibers loaded with carboxyl-multi-walled carbon nanotubes,while the inner layer is composed of highly aligned polycaprolactone fibers created by EHD printing.The tubular core of the HB-NGC is filled with hyaluronic acid methacryloyl(HAMA)hydrogel encapsulating bone marrow mesenchymal stem cells(BMSCs).This highly biomimetic NGC is conductive,capable of guiding axon growth,and sustainably releases growth factors,effectively mimicking the structure,function,and characteristics of natural peripheral nerves.Its distinctive architectural layers provide an exceptional bionic microenvironment by restoring physical pathways,facilitating electrical signal conduction,and supplying an extracellular matrix(ECM)environment enriched with essential growth factors.Additionally,the HB-NGC’s morphology,along with its physicochemical and mechanical properties,effectively bridges the gap between severed nerve ends.In vivo animal studies validate the HB-NGC’s effectiveness,highlighting its significant potential to enhance peripheral nerve regeneration.
基金Hunan Provincial Natural Science Foundation Youth Fund Project (2023JJ40480)Hunan Province Key Research and Development Program Project (2024JK2130)Outstanding Youth Project of Hunan University of Chinese Medicine (2022XJB003)。
文摘Objective To observe the effects of moxibustion at Huantiao(GB30)acupoint on nerve repair,regeneration,and function in rats with sciatic nerve injury(SNI),and explore the possible mechanism of SNI improvement via moxibustion.Methods A total of 70 specific pathogen-free(SPF)grade male Sprague-Dawley(SD)rats were randomly assigned to control group(n=10)and model group(n=60).Following replication of SNI to model group rats,60 SNI model rats were randomly allocated to SNI groups of 1 d,3 d,and 7 d and moxibustion groups of 1 d,3 d,and 7 d with 10 rats in each group.Moxibustion groups were given moxibustion at the Huantiao(GB30)acupoint on the affected side with a 5 cm distance from the skin under isoflurane respiratory anesthesia and treated once a day for 20 min for 1 d,3 d,and 7 d,respectively.Control and SNI groups were anesthetized with isoflurane daily for 20 min.Open field tests and thermal pain threshold tests were conducted,and the general condition of rats was observed in each group pre-modeling and on treatment day 1,3,and 7.At the end of the treatment,immunofluorescence was used to detect the axonal growth rate,axonal growth density,and Schwann cells(SCs)proliferation in the middle 1-mm cross-section of the crush injury segment in rats.The gastrocnemius muscles on both sides of the rats were taken and weighed to calculate the wet weight ratio of the gastrocnemius muscles on both sides to observe the muscle atrophy of the rats,and hematoxylin-eosin(HE)staining was used to observe the pathomorphological changes of the gastrocnemius muscles on the affected side.Quantitative real-time polymerase chain reaction(qPCR)was used to detect the expression levels of nerve growth factor(NGF),interferon(IFN),macrophage migration inhibitory factor(MIF),interleukin(IL)-4,and transforming growth factor(TGF)-βin the sciatic nerve tissue of the rats.Results After modeling,rats in both moxibustion and SNI groups showed typical signs of pain behaviors(bending and curling of the hind soles of the affected side,licking claws,and lameness)and decreased activity compared with control group.The main benefits of moxibustion were evident from day 3:compared with SNI group,rats in moxibustion group had marked relief of pain behavior,increased activity levels and movement,and a lower response to thermal pain.At the same time,moxibustion significantly promoted the repair of SNI,as evidenced by the significantly better axonal growth rate,growth density,and SCs proliferation density in the crush injury segment compared with SNI group(P<0.01).Moxibustion also regulated the local microenvironment of the injury,up-regulated the pro-nerve repair factors NGF,IL-4,and TGF-β(P<0.05),and down-regulated the pro-inflammatory factors IFN-γ(P<0.01)and MIF(P<0.05).By day 7,the histomorphology of the gastrocnemius muscle in moxibustion group was improved,as indicated by enlarged muscle fibers,elevated regular myocyte morphology and wet weight ratio of the affected and unaffected sides(P<0.05),as well as a sustained high expression levels of NGF,IL-4,and TGF-β(P<0.05,P<0.05,and P<0.01,respectively),and a maintenance of low level of IFN-γ(P<0.01).Concurrently,the MIF level was not significantly different from SNI group(P>0.05).Conclusion Moxibustion at the Huantiao(GB30)acupoint effectively improves motor function and promotes recovery of sensory function and nerve regeneration in SNI rats,which may be related to the regulation of local inflammatory response,the promotion of nerve growth factor expression,the improvement of regenerative microenvironment,and the acceleration of SCs proliferation and axonal growth rate in damaged nerves.
基金supported by the National Natural Science Foundation of China,Nos.31730031,32130060the National Natural Science Foundation of China,No.31971276(to JH)+1 种基金the Natural Science Foundation of Jiangsu Province,No.BK20202013(to XG)the Natural Science Foundation of Jiangsu Higher Education Institutions of China(Major Program),No.19KJA320005(to JH)。
文摘Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.
基金supported by the National Natural Science Foundation of China(82471067)Guangdong Basic and Applied Basic Research Foundation(2022A1515012168)+1 种基金Science and Technology Program of Guangzhou(202201020492)Open Research Funds of the State Key Laboratory of Ophthalmology(2023KF01).
文摘Retinal ganglion cells(RGCs)extend through the optic nerve,connecting with neurons in visually related nuclei.Similar to most mature neurons in the central nervous system,once damaged,RGCs are unable to regenerate their axons and swiftly progress to cell death.In addition to cell-intrinsic mechanisms,extrinsic factors within the extracellular environment,notably glial and inflammatory cells,exert a pivotal role in modulating RGC neurodegeneration and regeneration.Moreover,burgeoning evidence suggests that retinal interneurons,specifically amacrine cells,exert a substantial influence on RGC survival and axon regeneration.In this review,we consolidate the present understanding of extrinsic factors implicated in RGC survival and axon regeneration,and deliberate on potential therapeutic strategies aimed at fostering optic nerve regeneration and restoring vision.
基金supported by the National Natural Science Foundation of China,Nos.31971277 and 31950410551(both to DY)。
文摘Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells.However,axon regeneration and repair do not automatically result in the restoration of function,which is the ultimate therapeutic goal but also a major clinical challenge.Transforming growth factor(TGF)is a multifunctional cytokine that regulates various biological processes including tissue repair,embryo development,and cell growth and differentiation.There is accumulating evidence that TGF-βfamily proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells;recruiting specific immune cells;controlling the permeability of the blood-nerve barrier,thereby stimulating axon growth;and inhibiting remyelination of regenerated axons.TGF-βhas been applied to the treatment of peripheral nerve injury in animal models.In this context,we review the functions of TGF-βin peripheral nerve regeneration and potential clinical applications.
基金supported by a grant from National Key Basic Research Program of China(973 Program),No.2014CB542202a grant from Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)in China
文摘We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We obtained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function restoration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP.
基金supported by the Scientific Research Project of Huashan Hospital of Fudan University of China,No.2013QD05the National Natural Science Foundation of China,No.81501051&81572127
文摘Exogenous discharge can positively promote nerve repair. We, therefore, hypothesized that endogenous discharges may have similar effects. The phrenic nerve and intercostal nerve, controlled by the respiratory center, can emit regular nerve impulses; therefore these endogenous automatically discharging nerves might promote nerve regeneration. Action potential discharge patterns were examined in the diaphragm, external intercostal and latissimus dorsi muscles of rats. The phrenic and intercostal nerves showed rhythmic clusters of discharge, which were consistent with breathing frequency. From the first to the third intercostal nerves, spontaneous discharge amplitude was gradually increased. There was no obvious rhythmic discharge in the thoracodorsal nerve. Four animal groups were performed in rats as the musculocutaneous nerve cut and repaired was bland control. The other three groups were followed by a side-to-side anastomosis with the phrenic nerve, intercostal nerve and thoracodorsal nerve. Compound muscle action potentials in the biceps muscle innervated by the musculocutaneous nerve were recorded with electrodes. The tetanic forces of ipsilateral and contralateral biceps muscles were detected by a force displacement transducer. Wet muscle weight recovery rate was measured and pathological changes were observed using hematoxylin-eosin staining. The number of nerve fibers was observed using toluidine blue staining and changes in nerve ultrastructure were observed using transmission electron microscopy. The compound muscle action potential amplitude was significantly higher at 1 month after surgery in phrenic and intercostal nerve groups compared with the thoracodorsal nerve and blank control groups. The recovery rate of tetanic tension and wet weight of the right biceps were significantly lower at 2 months after surgery in the phrenic nerve, intercostal nerve, and thoracodorsal nerve groups compared with the negative control group. The number of myelinated axons distal to the coaptation site of the musculocutaneous nerve at 1 month after surgery was significantly higher in phrenic and intercostal nerve groups than in thoracodorsal nerve and negative control groups. These results indicate that endogenous autonomic discharge from phrenic and intercostal nerves can promote nerve regeneration in early stages after brachial plexus injury.
基金supported by grants from the National Natural Science Foundation of China,No.81872699(to MS)Key project of Shaanxi Province,China,No.2017ZDXM-SF-043(to MS)the Military Medical Science and Technology Youth Development Program,China,No.19QNP061(to CL)
文摘Olfactory ensheathing cells(OECs)are promising seed cells for nerve regeneration.However,their application is limited by the hypoxic environment usually present at the site of injury.Exosomes derived from human umbilical cord mesenchymal stem cells have the potential to regulate the pathological processes that occur in response to hypoxia.The ability of OECs to migrate is unknown,especially in hypoxic conditions,and the effect of OECs combined with exosomes on peripheral nerve repair is not clear.Better understanding of these issues will enable the potential of OECs for the treatment of nerve injury to be addressed.In this study,OECs were acquired from the olfactory bulb of Sprague Dawley rats.Human umbilical cord mesenchymal stem cell-derived exosomes(0–400μg/mL)were cultured with OECs for 12–48 hours.After culture with 400μg/mL exosomes for 24 hours,the viability and proliferation of OECs were significantly increased.We observed changes to OECs subjected to hypoxia for 24 hours and treatment with exosomes.Exosomes significantly promoted the survival and migration of OECs in hypoxic conditions,and effectively increased brain-derived neurotrophic factor gene expression,protein levels and secretion.Finally,using a 12 mm left sciatic nerve defect rat model,we confirmed that OECs and exosomes can synergistically promote motor and sensory function of the injured sciatic nerve.These findings show that application of OECs and exosomes can promote nerve regeneration and functional recovery.This study was approved by the Institutional Ethical Committee of the Air Force Medical University,China(approval No.IACUC-20181004)on October 7,2018;and collection and use of human umbilical cord specimens was approved by the Ethics Committee of the Linyi People’s Hospital,China(approval No.30054)on May 20,2019.
文摘Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen＇s method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord.
文摘The cornea has unique features that make it a useful model for regenerative medicine studies. It is an avascular, transparent, densely innervated tissue and any pathological changes can be easily detected by slit lamp examination. Corneal sensitivity is provided by the ophthalmic branch of the trigeminal nerve that elicits protective reflexes such as blinking and tearing and exerts trophic support by releasing neuromediators and growth factors. Corneal nerves are easily evaluated for both function and morphology using standard instruments such as corneal esthesiometer and in vivo confocal microscope. All local and systemic conditions that are associated with damage of the trigeminal nerve cause the development of neurotrophic keratitis, a rare degenerative disease. Neurotrophic keratitis is characterized by impairment of corneal sensitivity associated with development of persistent epithelial defects that may progress to corneal ulcer, melting and perforation. Current neurotrophic keratitis treatments aim at supporting corneal healing and preventing progression of corneal damage. Novel compounds able to stimulate corneal nerve recovery are in advanced development stage. Among them, nerve growth factor eye drops showed to be safe and effective in stimulating corneal healing and improving corneal sensitivity in patients with neurotrophic keratitis. Neurotrophic keratitis represents an useful model to evaluate in clinical practice novel neuro-regenerative drugs.
基金supported by Brazilian grants from Fundacao de Amparo à Pesquisa do Estado de Sao Paulo(FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)CAPES
文摘Studies have confirmed that bone marrow-derived mesenchymal stem cells （MSCs） can be used for treatment of several nervous system diseases. However, isolation of bone marrow-derived MSCs （BMSCs） is an invasive and painful process and the yield is very low. Therefore, there is a need to search for other alterative stem cell sources. Adipose-derived MSCs （ADSCs） have phenotypic and gene expression profiles similar to those of BMSCs. The production of ADSCs is greater than that of BMSCs, and ADSCs proliferate faster than BMSCs. To compare the effects of venous grafts containing BMSCs or ADSCs on sciatic nerve injury, in this study, rats were randomly divided into four groups： sham （only sciatic nerve exposed）, Matrigel （MG; sciatic nerve injury ＋ intravenous transplantation of MG vehicle）, ADSCs （sciatic nerve injury ＋ intravenous MG containing ADSCs）, and BMSCs （sciatic nerve injury ＋ intravenous MG containing BMSCs） groups. Sciatic functional index was calculated to evaluate the function of injured sciatic nerve. Morphologic characteristics of nerves distal to the lesion were observed by toluidine blue staining. Spinal motor neurons labeled with Fluoro-Gold were quantitatively assessed. Compared with sham-operated rats, sciatic functional index was lower, the density of small-diameter fibers was significantly increased, and the number of motor neurons significantly decreased in rats with sciatic nerve injury. Neither ADSCs nor BMSCs significantly improved the sciatic nerve function of rats with sciatic nerve injury,increased fiber density, fiber diameters, axonal diameters, myelin sheath thickness, and G ratios （axonal diameter/fiber diameter ratios） in the sciatic nerve distal to the lesion site. There was no significant difference in the number of spinal motor neurons among ADSCs, BMSCs and MG groups. These results suggest that neither BMSCs nor ADSCs provide satisfactory results for peripheral nerve repair when using MG as the conductor for engraftment.
基金the Korea Health R&D Project Granted by Ministry of Health and Welfare Republic of Korea, No. A080863
文摘BACKGROUND： Mesenchymal stem cells （MSCs） appear to be a good alternative to Schwann cells in the treatment of peripheral nerve injury. Fetal stem cells, like umbilical cord blood （UCB） and umbilical cord （UC） stem cells, have several advantages over adult stem cells. OBJECTIVE： To assess the effects of UC-derived MSCs （UCMSCs） and UCB-derived MSCs （UCBMSCs） in repair of sciatic nerve defects. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at the laboratory of Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, from July to December 2009. MATERIALS： UCMSCs were provided by the Research Institute of Biotechnology, Dongguk University. UCBMSCs were provided by the Laboratory of Stem Cells and Tumor Biology, College of Veterinary Medicine, Seoul National University. Dulbecco＇s modified Eagle＇s medium （DMEM） was purchased from Gibco-BRL, USA. METHODS： Seven-week-old Sprague-Dawley rats were randomly and evenly divided into three groups： DMEM, UCBMSCs, and UCMSCs. A 10-mm defect in the left sciatic nerve was constructed in all rats. DMEM （15 μL） containing 1×10^6 UCBMSCs or UCMSCs was injected into the gap between nerve stumps, with the surrounding epineurium as a natural conduit. For the DMEM group, simple DMEM was injected. MAIN OUTCOME MEASURES： At 7 weeks after sciatic nerve dissection, dorsal root ganglia neurons were labeled by fluorogold retrograde labeling. At 8 weeks, electrophysiology and histomorphometry were performed. At 2, 4, 6, and 8 weeks after surgery, sciatic nerve function was evaluated using gait analysis. RESULTS： The UCBMSCs group and the UCMSCs group exhibited similar sciatic nerve function and electrophysiological indices, which were better than the DMEM group, as measured by gait analysis （P 〈 0.05）. Fluorogold retrograde labeling of sciatic nerve revealed that the UCBMSCs group demonstrated a higher number of labeled neurons; however, the differences were not significant. Histomorphometric indices were similar in the UCBMSCs and UCMSCs groups, and total axon counts, particularly axon density （P 〈 0.05）, were significantly greater in the UCBMSCs and UCMSCs groups than in the DMEM group. CONCLUSION： Transplanting either UCBMSCs or UCMSCs into axotomized sciatic nerves could accelerate and promote sciatic nerve regeneration over 8 weeks. Both treatments had similar effects on nerve regeneration.
基金supported by grants from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542200the National Natural Science Foundation of China,No.31271284,81171146,31100860+1 种基金the Natural Science Foundation of Beijing of China,No.7142164Program for Innovative Research Team in University of Ministry of Education of China,No.IRT1201
文摘Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the ther- apeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly（lactic-co-glycolic acid） biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local ap- plication of icariin after spinal injury can promote peripheral nerve regeneration.
