Cystic lesions of peripheral nerves:Are we missing the diagnosis of the intraneural ganglion cyst?

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.

Security breach:peripheral nerves provide unrestricted access for toxin delivery into the central nervous system

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.

A NEW MODEL AND IMPROVED CABLE FUNCTION FOR REPRESENTING THE ACTIVATING PERIPHERAL NERVES BY A TRANSVERSE ELECTRIC FIELD DURING MAGNETIC STIMULATION

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.

The neural butterfly effect The injury to peripheral nerves changes the brain

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,

Bridging peripheral nerves using a deacetyl chitin conduit combined with short-term electrical stimulation

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.

Evaluation of a Novel Bioabsorbable PRGD/PDLLA/β-TCP/NGF Composites in Repair of Peripheral Nerves

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.

Long noncoding RNA H19 regulates degeneration and regeneration of injured peripheral nerves

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.

A Temporal–Spatial Atlas of Peripheral Nerve Evoked Cortex Potential in Rat:A Novel Testbed to Explore the Responding Patterns of the Brain to Peripheral Nerves

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.

IMMUNOGLOBULIN DEPOSITIONS IN PERIPHERAL NERVES IN POLYMYOSITIS

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.

miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically poor.We used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic nerves.We have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor recovery.Furthermore,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target muscles.In this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic nerve.Young adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of PEG.Compound action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury site.The success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days postoperatively.At 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish peroxidase.PEG-fusion repair reestablished axonal continuity.Compared to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal areas.Unexpectedly,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repair.This central reorganization may contribute to the improved behavioral recovery seen after PEG-fusion repair,supporting the use of this novel repair methodology over currently available treatments.

FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival

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.

Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary behaviors.The preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion repair.In the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats.Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws.Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections.Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex.Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats.Following sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury.However,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats.Furthermore,PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recove ry compared with those without Sciatic Functional Index recovery,suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries.This correlation was independent of the sex or strain of the rat.Furthermore,our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths.No chronic hypersensitivity developed in any rat up to 12 weeks.All these data suggest that PEG-fusion repair of transection peripheral nerve injuries co uld have important clinical benefits.

Autophagy-targeting modulation to promote peripheral nerve regeneration

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.

Advances in therapies using mesenchymal stem cells and their exosomes for treatment of peripheral nerve injury:state of the art and future perspectives

“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.

Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Bridging bioengineering and nanotechnology: Bone marrow derived mesenchymal stem cell-exosome solutions for peripheral nerve injury

Peripheral nerve injury(PNI)is a common disease that is difficult to nerve regeneration with current therapies.Fortunately,Zou et al demonstrated the role and mechanism of bone marrow derived mesenchymal stem cells(BMSCs)in promoting nerve regeneration,revealing broad prospects for BMSCs trans-plantation in alleviating PNI.We confirmed the fact that BMSCs significantly alleviate PNI,but there are shortcomings such as low cell survival rate and immune rejection,which limit the wide application of BMSCs.BMSCs-derived exosomes(Exos)are considered as a promising cell-free nanomedicine for PNI,avoiding the ethical issues of BMSCs.Exos in combination with bioengineering therapeutics(including extracellular matrix,hydrogel)brings new hope for PNI,provides a favorable microenvironment for neurological restoration and a therapeutic strategy with a favorable safety profile,significantly increases ex-pression of neurotrophic factors,promotes axonal and myelin regeneration,and demonstrates a strong potential to enhance neurogenesis.Therefore,engineered Exos exhibit better properties,such as stronger targeting and more beneficial components.This article briefly describes the role of nanotechnology and bioe-ngineering therapies for BMSCs in PNI,proposes clinical application prospects and challenges of nanotechnology and bioengineering BMSCs-derived Exos in PNI to improve the efficacy of BMSCs in the treatment of PNI.

Microsurgical decompression of the median nerves for treating diabetic peripheral neuropathy in the upper limbs: A 21-month follow-up

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.

GDNF to the rescue:GDNF delivery effects on motor neurons and nerves,and muscle re-innervation after peripheral nerve injuries

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.

Low-intensity pulsed ultrasound for regenerating peripheral nerves:potential for penile nerve

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.