AIM To highlight the salient magnetic resonance imaging(MRI) features of the intraneural ganglion cyst(INGC) of various peripheral nerves for their precise diagnosis and to differentiate them from other intra and extr...AIM To highlight the salient magnetic resonance imaging(MRI) features of the intraneural ganglion cyst(INGC) of various peripheral nerves for their precise diagnosis and to differentiate them from other intra and extraneural cystic lesions.METHODS A retrospective analysis of the magnetic resonance(MR) images of a cohort of 245 patients presenting with nerve palsy involving different peripheral nerves was done.MR images were analyzed for the presence of a nerve lesion,and if found,it was further characterized as solid or cystic.The serial axial,coronal and sagittal MR images of the lesions diagnosed as INGC were studied for their pattern and the anatomical extent along the course of the affected nerve and its branches.Its relation to identifiable anatomical landmarks,intraarticular communication and presence of denervation changes in the muscles supplied by involved nerve was also studied.RESULTS A total of 45 cystic lesions in the intra or extraneurallocations of the nerves were identified from the 245 MR scans done for patients presenting with nerve palsy.Out of these 45 cystic lesions,13 were diagnosed to have INGC of a peripheral nerve on MRI.The other cystic lesions included extraneural ganglion cyst,paralabral cyst impinging upon the suprascapular nerve,cystic schwannoma and nerve abscesses related to Hansen's disease involving various peripheral nerves.Thirteen lesions of INGC were identified in 12 patients.Seven of these affected the common peroneal nerve with one patient having a bilateral involvement.Two lesions each were noted in the tibial and suprascapular nerves,and one each in the obturator and proximal sciatic nerve.An intra-articular connection along the articular branch was demonstrated in 12 out of 13 lesions.Varying stages of denervation atrophy of the supplied muscles of the affected nerves were seen in 7 cases.Out of these 13 lesions in 12 patients,6 underwent surgery.CONCLUSION INGC is an important cause of reversible mono-neuropathy if diagnosed early and surgically treated.Its classic MRI pattern differentiates it from other lesions of the peripheral nerve and aid in its therapeutic planning.In each case,the joint connection has to be identified preoperatively,and the same should be excised during surgery to prevent further cyst recurrence.展开更多
We explore the hypothesis that a potential explanation for the initiation of motor neuron disease is an unappreciated vulnerability in central nervous system defense,the direct delivery of neurotoxins into motor neuro...We explore the hypothesis that a potential explanation for the initiation of motor neuron disease is an unappreciated vulnerability in central nervous system defense,the direct delivery of neurotoxins into motor neurons via peripheral nerve retrograde transport.This further suggests a mechanism for focal initiation of neuro-degenerative diseases in general,with subsequent spread by network degeneration as suggested by the Frost-Diamond hypothesis.We propose this vulnerability may be a byproduct of vertebrate evolution in a benign aquatic environment,where external surfaces were not exposed to concentrated neurotoxins.展开更多
Objective Previous studies of peripheral nerves activation during magnetic stimulation have focused almost exclusively on the cause of high external parallel electric field along the nerves, whereas the effect of the ...Objective Previous studies of peripheral nerves activation during magnetic stimulation have focused almost exclusively on the cause of high external parallel electric field along the nerves, whereas the effect of the transverse component has been ignored. In the present paper, the classical cable function is modified to represent the excitation of peripheral nerves stimulated by a transverse electric field during magnetic stimulation. Methods Responses of the Ranvier nodes to a transverse-field are thoroughly investigated by mathematic simulation. Results The simulation demonstrates that the excitation results from the net inward current driven by an external field. Based on a two-stage process, a novel model is introduced to describe peripheral nerves stimulated by a transverse-field. Based on the new model, the classical cable function is modified. Conclusion Using this modified cable equation, the excitation threshold of peripheral nerves in a transverse field during MS is obtained. The modified cable equation can be used to represent the response of peripheral nerves by an arbitrary electric field.展开更多
Regeneration of damaged innervations in the peripheral nervous system （PNS） has been well documented in both animals and human. After injury, the damaged neurite swells and undergoes retrograde degeneration. Once th...Regeneration of damaged innervations in the peripheral nervous system （PNS） has been well documented in both animals and human. After injury, the damaged neurite swells and undergoes retrograde degeneration. Once the debris is cleared, it begins to sprout and restore damaged connections. Damaged axons are able to regrow as long as the perikarya are intact and have made contact with the Schwann cells in the endoneurial channel[2]. Under appropriate conditions,展开更多
Peripheral nerve damage,such as that found after surgery or trauma,is a substantial clinical challenge.Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair ...Peripheral nerve damage,such as that found after surgery or trauma,is a substantial clinical challenge.Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury.In recent years,low-intensity pulsed ultrasound(LIPUS)has been studied as a potential method of stimulating peripheral nerve regeneration.In this review,the physiology of peripheral nerve regeneration is reviewed,and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed.Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms.These include an increase of neurotrophic factors,Schwann cell(SC)activation,cellular signaling activations,and induction of mitosis.We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models.We found numerous studies,suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes.Based on these findings,LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction.展开更多
Previous studies have demonstrated that deacetyl chitin conduit nerve bridging or electrical stimulation can effectively promote the regeneration of the injured peripheral nerve. We hypoth-esized that the combination ...Previous studies have demonstrated that deacetyl chitin conduit nerve bridging or electrical stimulation can effectively promote the regeneration of the injured peripheral nerve. We hypoth-esized that the combination of these two approaches could result in enhanced regeneration. Rats with right sciatic nerve injury were subjected to deacetyl chitin conduit bridging combined with electrical stimulation （0.1 ms, 3 V, 20 Hz, for 1 hour）. At 6 and 12 weeks after treatment, nerve conduction velocity, myelinated axon number, ifber diameter, axon diameter and the thickness of the myelin sheath in the stimulation group were better than in the non-stimulation group. The results indicate that deacetyl chitin conduit bridging combined with temporary electrical stimu-lation can promote peripheral nerve repair.展开更多
Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows...Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons.However,the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear.In this study,we established a Sprague-Dawley rat model of sciatic nerve transection injury.We performed in situ hybridization and found that at 4–7 days after sciatic nerve injury,lncRNA H19 was highly expressed.At 14 days before injury,adeno-associated virus was intrathecally injected into the L4–L5 foramina to disrupt or overexpress lncRNA H19.After overexpression of lncRNA H19,the growth of newly formed axons from the sciatic nerve was inhibited,whereas myelination was enhanced.Then,we performed gait analysis and thermal pain analysis to evaluate rat behavior.We found that lncRNA H19 overexpression delayed the recovery of rat behavior function,whereas interfering with lncRNA H19 expression improved functional recovery.Finally,we examined the expression of lncRNA H19 downstream target SEMA6D,and found that after lncRNA H19 overexpression,the SEMA6D protein level was increased.These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves.This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration.展开更多
Peripheral nerve regeneration using a novel nerve conduit （PRGD/PDLLA/β TCP/NGF） was evaluated, which was made of RGD peptide modified poly{（lactic acid）-co-[（glycolic acid）-alt-（L-lysine）]} （PRGD）, poly（d...Peripheral nerve regeneration using a novel nerve conduit （PRGD/PDLLA/β TCP/NGF） was evaluated, which was made of RGD peptide modified poly{（lactic acid）-co-[（glycolic acid）-alt-（L-lysine）]} （PRGD）, poly（d,l-lactic acid） （PDLLA） and β-tricalcium phosphate （β-TCP）. And the effectiveness was compared with that of PRGD/PDLLA/β-TCP, PDLLA and autograft in terms of nerve regeneration across a gap. Both of biodegradablity and cell-biocompatibility of the novel nerve conduit were evaluated in vitro. The results show that PRGD/PDLLA/β-TCP/NGF composite ma terials have better biodegradation properties and cell affinity than PDLLA, and could promote the RSC96 Schwann cells adhesion, proliferation and growth on the surface of materials. PRGD/PDLLA/ β-TCP/NGF composite conduit was significantly superior to that of the PDLLA conduit in histological and axon morphologic index. PRGD/PDLLA/β-TCP/NGF conduit is more beneficial to nerve regeneration than PDLLA conduit. The biodegradable PDLLA/PRGD/β-TCP/NGF conduit has a good biocompatibility with rats tissue and it could effectively promote the nerve regeneration after bridging sciatic nerve defect of rats, the effect is as good as that of the autograft nerve, significantly superior to the PRGD/PDLLA/β-TCP conduit and PDLLA conduit. PDLLA/PRGD/β-TCP/NGF composite conduit is a potential ideal conduit.展开更多
Observing the dynamic progress of the brain in response to peripheral nerve stimulation as a whole is the basis for a deeper understanding of overall brain function;however,it remains a great challenge.In this work,a ...Observing the dynamic progress of the brain in response to peripheral nerve stimulation as a whole is the basis for a deeper understanding of overall brain function;however,it remains a great challenge.In this work,a novel mini-invasive orthogonal recording method is developed to observe the overall evoked cortex potential(ECP)in rat brain.A typical ECP atlas with recognizable waveforms in the rat cortex corresponding to the median,ulnar,and radial nerve trunks and subdivided branches is acquired.Reproducible exciting temporal–spatial progress in the rat brain is obtained and visualized for the first time.Changes in the ECPs and exciting sequences in the cortex four months after median nerve transection are also observed.The results suggest that the brain’s response to peripheral stimulation has precise and reproducible temporal–spatial properties.This resource can serve as a testbed to explore the overall functional interaction and dynamic remodeling mechanisms between the peripheral and central nervous systems over time.展开更多
An immunocytochemical study was performed in 6 peripheral nerve specimens from 6 cases of polymyositis. The results revealed that depositions of IgG, IgM, IgA and C3 were found in the epineurium, perineurium and the w...An immunocytochemical study was performed in 6 peripheral nerve specimens from 6 cases of polymyositis. The results revealed that depositions of IgG, IgM, IgA and C3 were found in the epineurium, perineurium and the walls of capillaries. These findings demonstrated that depositions of immunoglobulins and the complement-mediated immunoreaction may play an important role in pathogenesis of polymyositis with peripheral nerve involvements.展开更多
After peripheral nerve injury,disruption of immune homeostasis retards the repair process of peripheral nerves.Piezoelectric materials are the latest paradigm used to address the electrical and energy deficiencies of ...After peripheral nerve injury,disruption of immune homeostasis retards the repair process of peripheral nerves.Piezoelectric materials are the latest paradigm used to address the electrical and energy deficiencies of peripheral nerves.However,the effects and mechanism by which piezoelectric materials regulate immune homeostasis and promote peripheral nerve regeneration remain unclear.We developed a self-powered nerve-bridging scaffold by adding polyvinylidene fluoride-trifluoroethylene(P(VDF-TrFE))and reduced graphene oxide(rGO)nanoparticles to a polycaprolactone(PCL)substrate.This electrical stimulation reduces high levels of inflammatory cytokines in damaged nerve tissue,controls abnormal neutrophil activity,and promotes quick revascularization.By providing energy,immune balance,and angiogenesis,this electroactive scaffold significantly enhances peripheral nerve regeneration.The recovery of the disintegrated myelin sheath was comparable to that observed after autologous nerve transplantation,and neuromuscular function was significantly restored after implantation of the self-generating electrical stimulation material.This multifunctional fibrous material has promise for clinical translation for the treatment of 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
Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells en...Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells encounter various obstacles,including limited tissue sources,invasive acquisition methods,cellular heterogeneity,purification challenges,cellular senescence,and diminished pluripotency and proliferation over successive passages.In this study,we used induced pluripotent stem cell-derived mesenchymal stem cells,known for their self-renewal capacity,multilineage differentiation potential,and immunomodulatory characteristics.We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury.Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation.Furthermore,the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats.Additionally,our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization.Collectively,our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats,offering promising therapeutic strategies for clinical translation.展开更多
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
BACKGROUND： Peripheral nerve injured by abnormal glucose metabolism is compressed, which is an important etiological factor of diabetic peripheral neuropathy （DPN）. Microsurgical decompression of peripheral nerve m...BACKGROUND： Peripheral nerve injured by abnormal glucose metabolism is compressed, which is an important etiological factor of diabetic peripheral neuropathy （DPN）. Microsurgical decompression of peripheral nerve maybe effectively releases the symptoms of DPN. OBJECTIVE： To investigate the curative effects of microsurgical decompression of median nerves for treatment of DPN in upper limbs. DESIGN： Case-follow up observation. SETTING： Department of Orthopaedics, Department of Neurosurgery, China-Japan Friendship Hospital, Ministry of Health. PARTICIPANTS： Twelve patients with DPN in upper limbs （19 hands） who received treatment in the Department of Orthopaedics, Department of Neurosurgery, China-Japan Friendship Hospital, Ministry of Public Health between March 2004 and July 2006 were involved in this experiment. The involved patients, 5 male and 7 female, were aged 44 to 77 years, with DPN course of 6 months to 16 years. They all met 1999 WHO diabetic diagnosis criteria. Both two hands had symptom in 7 patients, and only one hand had symptom in 5 patients. Informed consents of detected items were obtained from all the patients, who also received 21 months of follow-up treatment. METHODS： （1）Operation was carried out under the anesthetic status of brachial plexus. Under an operating microscope, transverse carpal ligament was exposed. Subsequently, transverse carpal ligament, forearm superficial fascia and palmar aponeurosis were fully liberated, and then part of them was cut off. Connective tissue around median nerve, superficial flexor muscle of fingers, radial flexor, palmaris longus and other flexor tendons were completely loosened. Finally, epineurium was opened with microinstrument for neurolysis. After tourniquet was loosened, and bipolar coagulator was used to stop bleeding, and the incision was closed. （2） In postoperative 21 months, the subjective symptom, two-point discrimination （The smallest distance of two normal points was 3 to 6 mm）, nerve conduction velocity and action potential amplitude （short abductor muscle of thumb end Lat 〈 4.5 ms; Motor nerve conduction velocity of forearm 〉 50 m/s）, etc. of all the patients were followed up. MAIN OUTCOME MEASURES＂ The objective evaluation and long-term follow up of curative effect of microsurgical decompression of median nerves for treatment of DPN in upper limbs. RESULTS： Twelve patients with DPN in upper limbs participated in the final analysis. （1） After operation, numbness and pain symptom releasing 100% were found in 19 hands of 12 patients with DPN. During follow up, numbness and recrudescent pain symptom were found in one hand （5%, 1/19）. （2）Postoperatively, index finger two point discrimination in 15 （94%, 15/16） hands recovered to normal. （3） nerve conduction velocity and action potential amplitude improved completely. （4） Two hands （2/19, 10% ）had poor healing at incision, and they late healed at postoperative 1 and 1.5 months, respectively. CONCLUSION： Long-term follow-up results show that microsurgical decompression is an effective method to treat DPN in upper limbs.展开更多
Peripheral nerve injuries commonly occur due to trauma,like a traffic accident.Peripheral nerves get severed,causing motor neuron death and potential muscle atrophy.The current golden standard to treat peripheral nerv...Peripheral nerve injuries commonly occur due to trauma,like a traffic accident.Peripheral nerves get severed,causing motor neuron death and potential muscle atrophy.The current golden standard to treat peripheral nerve lesions,especially lesions with large(≥3 cm)nerve gaps,is the use of a nerve autograft or reimplantation in cases where nerve root avulsions occur.If not tended early,degeneration of motor neurons and loss of axon regeneration can occur,leading to loss of function.Although surgical procedures exist,patients often do not fully recover,and quality of life deteriorates.Peripheral nerves have limited regeneration,and it is usually mediated by Schwann cells and neurotrophic factors,like glial cell line-derived neurotrophic factor,as seen in Wallerian degeneration.Glial cell line-derived neurotrophic factor is a neurotrophic factor known to promote motor neuron survival and neurite outgrowth.Glial cell line-derived neurotrophic factor is upregulated in different forms of nerve injuries like axotomy,sciatic nerve crush,and compression,thus creating great interest to explore this protein as a potential treatment for peripheral nerve injuries.Exogenous glial cell line-derived neurotrophic factor has shown positive effects in regeneration and functional recovery when applied in experimental models of peripheral nerve injuries.In this review,we discuss the mechanism of repair provided by Schwann cells and upregulation of glial cell line-derived neurotrophic factor,the latest findings on the effects of glial cell line-derived neurotrophic factor in different types of peripheral nerve injuries,delivery systems,and complementary treatments(electrical muscle stimulation and exercise).Understanding and overcoming the challenges of proper timing and glial cell line-derived neurotrophic factor delivery is paramount to creating novel treatments to tend to peripheral nerve injuries to improve patients'quality of life.展开更多
In China, there are approximately 20 million people suffering from peripheral nerve injury and this number is increasing at a rate of 2 million per year. These patients cannot live or work independently and are a heav...In China, there are approximately 20 million people suffering from peripheral nerve injury and this number is increasing at a rate of 2 million per year. These patients cannot live or work independently and are a heavy responsibility on both family and society because of extreme disability and dysfunction caused by peripheral nerve injury （PNI）. Thus, repair of PNI has become a major public health issue in China.展开更多
Objective ： To introduce a practical, economical, and time-saving method to stain （with osmic acid） the myelin sheath in normal and regenerated peripheral nerves. Methods： A total of 12 Sprague Dawley rats, weighi...Objective ： To introduce a practical, economical, and time-saving method to stain （with osmic acid） the myelin sheath in normal and regenerated peripheral nerves. Methods： A total of 12 Sprague Dawley rats, weighing 250-320 g （ mecan = 276 g ± 38 g ）, were divided into two groups： a normal nerve group （n = 6 ） and a regenerated nerve group （ n = 6 ）. In the normal nerve group, the ventral and dorsal roots of L4 to L6 and their sciatic nerves were harvested for histological analysis. While in the regenerated nerve group, the right sciatic nerves were severed and then repaired with an epineurial microsuture method. The repaired nerves were harvested 12 weeks postoperatively. All the specimens were fixed in 4 % paraformaldehyde and transferred to 2 % osmic acid for 3-5 days. Then the specimens were kept in 75% alcohol before being embedded in paraffin. The tissues were cut into sections of 3 ten in thickness with a conventional microtome. Results： Under a light microscope, myelin sheaths were clearly visible at all magnifications in both groups. They were stained in clear dark colour with a light yellow or colorless background, which provided high contrast images to allow reliable morphometric measurements. Morphological assessment was made in both normal and regenerated sciatic nerves. The ratios of the myelin area to the fibre area were 60. 28 % ± 7.66 % in the normal nerve group and 51. 67% ± 6. 85% in the regenerated nerve group, respectively （P〈0.01）. Conclusions： Osmic acid staining is easy to perform and a very clear image for morphometrical assessment is easy to obtain. Therefore, it is a reliable technique for quantitative evaluation of nerve morphology.展开更多
Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulat...Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.展开更多
“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal cord.Peripheral nerve injury results in movements or sensation impairments,and represents a serious public health pro...“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal cord.Peripheral nerve injury results in movements or sensation impairments,and represents a serious public health problem.Although severed peripheral nerves have been effectively joined and various therapies have been offered,recovery of sensory or motor functions remains limited,and efficacious therapies for complete repair of a nerve injury remain elusive.The emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and function.Mesenchymal stem cells,as large living cells responsive to the environment,secrete various factors and exosomes.The latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins,microRNA,and messenger RNA derived from parent mesenchymal stem cells.Exosomes have pivotal roles in cell-to-cell communication and nervous tissue function,offering solutions to changes associated with cell-based therapies.Despite ongoing investigations,mesenchymal stem cells and mesenchymal stem cell-derived exosome-based therapies are in the exploratory stage.A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical translation.This review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in peripheral nerve injury,exploring the underlying mechanisms.Subsequently,it provides an overview of the current status of mesenchymal stem cell and exosomebased therapies in clinical trials,followed by a comparative analysis of therapies utilizing mesenchymal stem cells and exosomes.Finally,the review addresses the limitations and challenges associated with use of mesenchymal stem cell-derived exosomes,offering potential solutions and guiding future directions.展开更多
文摘AIM To highlight the salient magnetic resonance imaging(MRI) features of the intraneural ganglion cyst(INGC) of various peripheral nerves for their precise diagnosis and to differentiate them from other intra and extraneural cystic lesions.METHODS A retrospective analysis of the magnetic resonance(MR) images of a cohort of 245 patients presenting with nerve palsy involving different peripheral nerves was done.MR images were analyzed for the presence of a nerve lesion,and if found,it was further characterized as solid or cystic.The serial axial,coronal and sagittal MR images of the lesions diagnosed as INGC were studied for their pattern and the anatomical extent along the course of the affected nerve and its branches.Its relation to identifiable anatomical landmarks,intraarticular communication and presence of denervation changes in the muscles supplied by involved nerve was also studied.RESULTS A total of 45 cystic lesions in the intra or extraneurallocations of the nerves were identified from the 245 MR scans done for patients presenting with nerve palsy.Out of these 45 cystic lesions,13 were diagnosed to have INGC of a peripheral nerve on MRI.The other cystic lesions included extraneural ganglion cyst,paralabral cyst impinging upon the suprascapular nerve,cystic schwannoma and nerve abscesses related to Hansen's disease involving various peripheral nerves.Thirteen lesions of INGC were identified in 12 patients.Seven of these affected the common peroneal nerve with one patient having a bilateral involvement.Two lesions each were noted in the tibial and suprascapular nerves,and one each in the obturator and proximal sciatic nerve.An intra-articular connection along the articular branch was demonstrated in 12 out of 13 lesions.Varying stages of denervation atrophy of the supplied muscles of the affected nerves were seen in 7 cases.Out of these 13 lesions in 12 patients,6 underwent surgery.CONCLUSION INGC is an important cause of reversible mono-neuropathy if diagnosed early and surgically treated.Its classic MRI pattern differentiates it from other lesions of the peripheral nerve and aid in its therapeutic planning.In each case,the joint connection has to be identified preoperatively,and the same should be excised during surgery to prevent further cyst recurrence.
基金supported by grants from the New Jersey Commission on Spinal Cord Research (05-304711-015)
文摘We explore the hypothesis that a potential explanation for the initiation of motor neuron disease is an unappreciated vulnerability in central nervous system defense,the direct delivery of neurotoxins into motor neurons via peripheral nerve retrograde transport.This further suggests a mechanism for focal initiation of neuro-degenerative diseases in general,with subsequent spread by network degeneration as suggested by the Frost-Diamond hypothesis.We propose this vulnerability may be a byproduct of vertebrate evolution in a benign aquatic environment,where external surfaces were not exposed to concentrated neurotoxins.
文摘Objective Previous studies of peripheral nerves activation during magnetic stimulation have focused almost exclusively on the cause of high external parallel electric field along the nerves, whereas the effect of the transverse component has been ignored. In the present paper, the classical cable function is modified to represent the excitation of peripheral nerves stimulated by a transverse electric field during magnetic stimulation. Methods Responses of the Ranvier nodes to a transverse-field are thoroughly investigated by mathematic simulation. Results The simulation demonstrates that the excitation results from the net inward current driven by an external field. Based on a two-stage process, a novel model is introduced to describe peripheral nerves stimulated by a transverse-field. Based on the new model, the classical cable function is modified. Conclusion Using this modified cable equation, the excitation threshold of peripheral nerves in a transverse field during MS is obtained. The modified cable equation can be used to represent the response of peripheral nerves by an arbitrary electric field.
文摘Regeneration of damaged innervations in the peripheral nervous system （PNS） has been well documented in both animals and human. After injury, the damaged neurite swells and undergoes retrograde degeneration. Once the debris is cleared, it begins to sprout and restore damaged connections. Damaged axons are able to regrow as long as the perikarya are intact and have made contact with the Schwann cells in the endoneurial channel[2]. Under appropriate conditions,
基金Army,Navy,NIH,Air Force,VA and Health Affairs to support the AFIRM II effort,under Award number W81XWH-13-2-0052,and NIDDK of the National Institutes of Health under award nu 1m ber er 1R01DK105097-01A1The U.S.Army Medical Research Acquisition Activity,820 Chandler Street,Fort Detrick MD 21702-5014。
文摘Peripheral nerve damage,such as that found after surgery or trauma,is a substantial clinical challenge.Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury.In recent years,low-intensity pulsed ultrasound(LIPUS)has been studied as a potential method of stimulating peripheral nerve regeneration.In this review,the physiology of peripheral nerve regeneration is reviewed,and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed.Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms.These include an increase of neurotrophic factors,Schwann cell(SC)activation,cellular signaling activations,and induction of mitosis.We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models.We found numerous studies,suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes.Based on these findings,LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction.
基金funded by National Program on Key Basic Research Project of China(973 Program),No.2014CB542200the National Natural Science Foundation of China,No.31171150,31271284,30801169+2 种基金the Chinese Educational Ministry New Century Excellent Talent Support Project,No.BMU20110270the Beijing City Science&Technology New Star Classification,No.2008A010the Ministry of Education New Teachers of Institutions of Higher Learning Doctoral Fund,No.20070001780
文摘Previous studies have demonstrated that deacetyl chitin conduit nerve bridging or electrical stimulation can effectively promote the regeneration of the injured peripheral nerve. We hypoth-esized that the combination of these two approaches could result in enhanced regeneration. Rats with right sciatic nerve injury were subjected to deacetyl chitin conduit bridging combined with electrical stimulation （0.1 ms, 3 V, 20 Hz, for 1 hour）. At 6 and 12 weeks after treatment, nerve conduction velocity, myelinated axon number, ifber diameter, axon diameter and the thickness of the myelin sheath in the stimulation group were better than in the non-stimulation group. The results indicate that deacetyl chitin conduit bridging combined with temporary electrical stimu-lation can promote peripheral nerve repair.
基金supported by the National Natural Science Foundation of China,Nos.31971277(to DBY),31950410551(to DBY)Scientific Research Foundation for Returned Scholars,Ministry of Education of China(to DBY)+2 种基金a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(to DBY)the Postgraduate Research&Practice Innovation Program of Jiangsu Province of China,No.KYCX 19-2050(to JS)Jiangsu College Students’Innovation and Entrepreneurship Training Program,No.202213993005Y(to YY)。
文摘Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons.However,the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear.In this study,we established a Sprague-Dawley rat model of sciatic nerve transection injury.We performed in situ hybridization and found that at 4–7 days after sciatic nerve injury,lncRNA H19 was highly expressed.At 14 days before injury,adeno-associated virus was intrathecally injected into the L4–L5 foramina to disrupt or overexpress lncRNA H19.After overexpression of lncRNA H19,the growth of newly formed axons from the sciatic nerve was inhibited,whereas myelination was enhanced.Then,we performed gait analysis and thermal pain analysis to evaluate rat behavior.We found that lncRNA H19 overexpression delayed the recovery of rat behavior function,whereas interfering with lncRNA H19 expression improved functional recovery.Finally,we examined the expression of lncRNA H19 downstream target SEMA6D,and found that after lncRNA H19 overexpression,the SEMA6D protein level was increased.These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves.This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration.
基金Funded by 973 State Key Fundamental Research and Development (No.G2005CB623905)
文摘Peripheral nerve regeneration using a novel nerve conduit （PRGD/PDLLA/β TCP/NGF） was evaluated, which was made of RGD peptide modified poly{（lactic acid）-co-[（glycolic acid）-alt-（L-lysine）]} （PRGD）, poly（d,l-lactic acid） （PDLLA） and β-tricalcium phosphate （β-TCP）. And the effectiveness was compared with that of PRGD/PDLLA/β-TCP, PDLLA and autograft in terms of nerve regeneration across a gap. Both of biodegradablity and cell-biocompatibility of the novel nerve conduit were evaluated in vitro. The results show that PRGD/PDLLA/β-TCP/NGF composite ma terials have better biodegradation properties and cell affinity than PDLLA, and could promote the RSC96 Schwann cells adhesion, proliferation and growth on the surface of materials. PRGD/PDLLA/ β-TCP/NGF composite conduit was significantly superior to that of the PDLLA conduit in histological and axon morphologic index. PRGD/PDLLA/β-TCP/NGF conduit is more beneficial to nerve regeneration than PDLLA conduit. The biodegradable PDLLA/PRGD/β-TCP/NGF conduit has a good biocompatibility with rats tissue and it could effectively promote the nerve regeneration after bridging sciatic nerve defect of rats, the effect is as good as that of the autograft nerve, significantly superior to the PRGD/PDLLA/β-TCP conduit and PDLLA conduit. PDLLA/PRGD/β-TCP/NGF composite conduit is a potential ideal conduit.
基金the National Natural Science Foundation of China(82072162 and 81971177)the Beijing Municipal Natural Science Foundation(7192215).
文摘Observing the dynamic progress of the brain in response to peripheral nerve stimulation as a whole is the basis for a deeper understanding of overall brain function;however,it remains a great challenge.In this work,a novel mini-invasive orthogonal recording method is developed to observe the overall evoked cortex potential(ECP)in rat brain.A typical ECP atlas with recognizable waveforms in the rat cortex corresponding to the median,ulnar,and radial nerve trunks and subdivided branches is acquired.Reproducible exciting temporal–spatial progress in the rat brain is obtained and visualized for the first time.Changes in the ECPs and exciting sequences in the cortex four months after median nerve transection are also observed.The results suggest that the brain’s response to peripheral stimulation has precise and reproducible temporal–spatial properties.This resource can serve as a testbed to explore the overall functional interaction and dynamic remodeling mechanisms between the peripheral and central nervous systems over time.
文摘An immunocytochemical study was performed in 6 peripheral nerve specimens from 6 cases of polymyositis. The results revealed that depositions of IgG, IgM, IgA and C3 were found in the epineurium, perineurium and the walls of capillaries. These findings demonstrated that depositions of immunoglobulins and the complement-mediated immunoreaction may play an important role in pathogenesis of polymyositis with peripheral nerve involvements.
基金supported by the National Key R&D Program of China(No.2021YFC2400800)the Projects of the National Natural Science Foundation of China(Nos.82072452,82272475,and 82372409)+5 种基金the Science and Technology Commission of Shanghai Municipality(No.20DZ2254900)the Sino-German Mobility Programme(No.M-0699)the Excellent Youth Cultivation Program of Shanghai Sixth People’s Hospital(No.ynyq202201)the Medical Engineering Co-Project of University of Shanghai for Science and Technology(10-22-310-520)a grant from the Shanghai Municipal Health Commission(No.202040399)the Laboratory Open Fund of Key Technology and Materials in Minimally Invasive Spine Surgery(2024JZWC-ZDA05).
文摘After peripheral nerve injury,disruption of immune homeostasis retards the repair process of peripheral nerves.Piezoelectric materials are the latest paradigm used to address the electrical and energy deficiencies of peripheral nerves.However,the effects and mechanism by which piezoelectric materials regulate immune homeostasis and promote peripheral nerve regeneration remain unclear.We developed a self-powered nerve-bridging scaffold by adding polyvinylidene fluoride-trifluoroethylene(P(VDF-TrFE))and reduced graphene oxide(rGO)nanoparticles to a polycaprolactone(PCL)substrate.This electrical stimulation reduces high levels of inflammatory cytokines in damaged nerve tissue,controls abnormal neutrophil activity,and promotes quick revascularization.By providing energy,immune balance,and angiogenesis,this electroactive scaffold significantly enhances peripheral nerve regeneration.The recovery of the disintegrated myelin sheath was comparable to that observed after autologous nerve transplantation,and neuromuscular function was significantly restored after implantation of the self-generating electrical stimulation material.This multifunctional fibrous material has promise for clinical translation for the treatment of 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supported by the National Natural Science Foundation of China,No.32171356(to YW)Self-Support Research Projects of Shihezi University,No.ZZZC2021105(to WJ)+1 种基金Capital Medical University Natural Science Cultivation Fund,No.PYZ23044(to FQM)Beijing Municipal Natural Science Foundation,No.7244410(to JHD)。
文摘Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells encounter various obstacles,including limited tissue sources,invasive acquisition methods,cellular heterogeneity,purification challenges,cellular senescence,and diminished pluripotency and proliferation over successive passages.In this study,we used induced pluripotent stem cell-derived mesenchymal stem cells,known for their self-renewal capacity,multilineage differentiation potential,and immunomodulatory characteristics.We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury.Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation.Furthermore,the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats.Additionally,our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization.Collectively,our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats,offering promising therapeutic strategies for clinical translation.
基金supported 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the Scientific Research Program of China-Japan Friendship Hospital, Ministry of Health, No. 20053055
文摘BACKGROUND： Peripheral nerve injured by abnormal glucose metabolism is compressed, which is an important etiological factor of diabetic peripheral neuropathy （DPN）. Microsurgical decompression of peripheral nerve maybe effectively releases the symptoms of DPN. OBJECTIVE： To investigate the curative effects of microsurgical decompression of median nerves for treatment of DPN in upper limbs. DESIGN： Case-follow up observation. SETTING： Department of Orthopaedics, Department of Neurosurgery, China-Japan Friendship Hospital, Ministry of Health. PARTICIPANTS： Twelve patients with DPN in upper limbs （19 hands） who received treatment in the Department of Orthopaedics, Department of Neurosurgery, China-Japan Friendship Hospital, Ministry of Public Health between March 2004 and July 2006 were involved in this experiment. The involved patients, 5 male and 7 female, were aged 44 to 77 years, with DPN course of 6 months to 16 years. They all met 1999 WHO diabetic diagnosis criteria. Both two hands had symptom in 7 patients, and only one hand had symptom in 5 patients. Informed consents of detected items were obtained from all the patients, who also received 21 months of follow-up treatment. METHODS： （1）Operation was carried out under the anesthetic status of brachial plexus. Under an operating microscope, transverse carpal ligament was exposed. Subsequently, transverse carpal ligament, forearm superficial fascia and palmar aponeurosis were fully liberated, and then part of them was cut off. Connective tissue around median nerve, superficial flexor muscle of fingers, radial flexor, palmaris longus and other flexor tendons were completely loosened. Finally, epineurium was opened with microinstrument for neurolysis. After tourniquet was loosened, and bipolar coagulator was used to stop bleeding, and the incision was closed. （2） In postoperative 21 months, the subjective symptom, two-point discrimination （The smallest distance of two normal points was 3 to 6 mm）, nerve conduction velocity and action potential amplitude （short abductor muscle of thumb end Lat 〈 4.5 ms; Motor nerve conduction velocity of forearm 〉 50 m/s）, etc. of all the patients were followed up. MAIN OUTCOME MEASURES＂ The objective evaluation and long-term follow up of curative effect of microsurgical decompression of median nerves for treatment of DPN in upper limbs. RESULTS： Twelve patients with DPN in upper limbs participated in the final analysis. （1） After operation, numbness and pain symptom releasing 100% were found in 19 hands of 12 patients with DPN. During follow up, numbness and recrudescent pain symptom were found in one hand （5%, 1/19）. （2）Postoperatively, index finger two point discrimination in 15 （94%, 15/16） hands recovered to normal. （3） nerve conduction velocity and action potential amplitude improved completely. （4） Two hands （2/19, 10% ）had poor healing at incision, and they late healed at postoperative 1 and 1.5 months, respectively. CONCLUSION： Long-term follow-up results show that microsurgical decompression is an effective method to treat DPN in upper limbs.
基金funded by the NIH Grant 1R15AG022908-01A2 and the Western Michigan University(to JMS)。
文摘Peripheral nerve injuries commonly occur due to trauma,like a traffic accident.Peripheral nerves get severed,causing motor neuron death and potential muscle atrophy.The current golden standard to treat peripheral nerve lesions,especially lesions with large(≥3 cm)nerve gaps,is the use of a nerve autograft or reimplantation in cases where nerve root avulsions occur.If not tended early,degeneration of motor neurons and loss of axon regeneration can occur,leading to loss of function.Although surgical procedures exist,patients often do not fully recover,and quality of life deteriorates.Peripheral nerves have limited regeneration,and it is usually mediated by Schwann cells and neurotrophic factors,like glial cell line-derived neurotrophic factor,as seen in Wallerian degeneration.Glial cell line-derived neurotrophic factor is a neurotrophic factor known to promote motor neuron survival and neurite outgrowth.Glial cell line-derived neurotrophic factor is upregulated in different forms of nerve injuries like axotomy,sciatic nerve crush,and compression,thus creating great interest to explore this protein as a potential treatment for peripheral nerve injuries.Exogenous glial cell line-derived neurotrophic factor has shown positive effects in regeneration and functional recovery when applied in experimental models of peripheral nerve injuries.In this review,we discuss the mechanism of repair provided by Schwann cells and upregulation of glial cell line-derived neurotrophic factor,the latest findings on the effects of glial cell line-derived neurotrophic factor in different types of peripheral nerve injuries,delivery systems,and complementary treatments(electrical muscle stimulation and exercise).Understanding and overcoming the challenges of proper timing and glial cell line-derived neurotrophic factor delivery is paramount to creating novel treatments to tend to peripheral nerve injuries to improve patients'quality of life.
基金supported by grants from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542200Program for Innovative Research Team in University of Ministry of Education of China,No.IRT1201+1 种基金the National Natural Science Foundation of China,No.31271284,31171150,81171146,30971526,31100860,31040043Program for New Century Excellent Talents in University of Ministry of Education of China,No.BMU20110270
文摘In China, there are approximately 20 million people suffering from peripheral nerve injury and this number is increasing at a rate of 2 million per year. These patients cannot live or work independently and are a heavy responsibility on both family and society because of extreme disability and dysfunction caused by peripheral nerve injury （PNI）. Thus, repair of PNI has become a major public health issue in China.
基金This study was supported by the National Natural Science Foundation of China （ No. 39700141 ） and Foshan Science and Technology Committee （ No. 03080051 ）.
文摘Objective ： To introduce a practical, economical, and time-saving method to stain （with osmic acid） the myelin sheath in normal and regenerated peripheral nerves. Methods： A total of 12 Sprague Dawley rats, weighing 250-320 g （ mecan = 276 g ± 38 g ）, were divided into two groups： a normal nerve group （n = 6 ） and a regenerated nerve group （ n = 6 ）. In the normal nerve group, the ventral and dorsal roots of L4 to L6 and their sciatic nerves were harvested for histological analysis. While in the regenerated nerve group, the right sciatic nerves were severed and then repaired with an epineurial microsuture method. The repaired nerves were harvested 12 weeks postoperatively. All the specimens were fixed in 4 % paraformaldehyde and transferred to 2 % osmic acid for 3-5 days. Then the specimens were kept in 75% alcohol before being embedded in paraffin. The tissues were cut into sections of 3 ten in thickness with a conventional microtome. Results： Under a light microscope, myelin sheaths were clearly visible at all magnifications in both groups. They were stained in clear dark colour with a light yellow or colorless background, which provided high contrast images to allow reliable morphometric measurements. Morphological assessment was made in both normal and regenerated sciatic nerves. The ratios of the myelin area to the fibre area were 60. 28 % ± 7.66 % in the normal nerve group and 51. 67% ± 6. 85% in the regenerated nerve group, respectively （P〈0.01）. Conclusions： Osmic acid staining is easy to perform and a very clear image for morphometrical assessment is easy to obtain. Therefore, it is a reliable technique for quantitative evaluation of nerve morphology.
基金supported by the National Natural Science Foundation of China,Nos.82271411(to RG),51803072(to WLiu)grants from the Department of Finance of Jilin Province,Nos.2022SCZ25(to RG),2022SCZ10(to WLiu),2021SCZ07(to RG)+2 种基金Jilin Provincial Science and Technology Program,No.YDZJ202201ZYTS038(to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University,No.2022qnpy11(to WLuo)The Project of China-Japan Union Hospital of Jilin University,No.XHQMX20233(to RG)。
文摘Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.
基金supported by the Key Research and Development Project of Hubei Province of China,2022BCA028(to HC)。
文摘“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal cord.Peripheral nerve injury results in movements or sensation impairments,and represents a serious public health problem.Although severed peripheral nerves have been effectively joined and various therapies have been offered,recovery of sensory or motor functions remains limited,and efficacious therapies for complete repair of a nerve injury remain elusive.The emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and function.Mesenchymal stem cells,as large living cells responsive to the environment,secrete various factors and exosomes.The latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins,microRNA,and messenger RNA derived from parent mesenchymal stem cells.Exosomes have pivotal roles in cell-to-cell communication and nervous tissue function,offering solutions to changes associated with cell-based therapies.Despite ongoing investigations,mesenchymal stem cells and mesenchymal stem cell-derived exosome-based therapies are in the exploratory stage.A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical translation.This review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in peripheral nerve injury,exploring the underlying mechanisms.Subsequently,it provides an overview of the current status of mesenchymal stem cell and exosomebased therapies in clinical trials,followed by a comparative analysis of therapies utilizing mesenchymal stem cells and exosomes.Finally,the review addresses the limitations and challenges associated with use of mesenchymal stem cell-derived exosomes,offering potential solutions and guiding future directions.
