Temporomandibular joint osteoarthritis(TMJ-OA)is a common disease often accompanied by pain,seriously affecting physical and mental health of patients.Abnormal innervation at the osteochondral junction has been consid...Temporomandibular joint osteoarthritis(TMJ-OA)is a common disease often accompanied by pain,seriously affecting physical and mental health of patients.Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia,while the specific mechanism mediating pain remains unclear.To investigate the underlying mechanism of TMJ-OA pain,an abnormal joint loading model was used to induce TMJ-OA pain.We found that during the development of TMJ-OA,the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves.Furthermore,these two types of nerves are spatially closely associated.Additionally,it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice,whereas blocking these signals effectively alleviates pain.In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons.Moreover,we also discovered that through releasing norepinephrine,regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators.This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA.It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves,providing a potential target for treating TMJ-OA pain.展开更多
Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-...Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-derived substance P could induce apoptosis in breast cancer cells that overexpressed tachykinin receptors.Single-stranded RNAs(ssRNAs)leaking from dying cells subsequently interact with toll-like receptor 7(TLR7)on other cancer cells and finally promoted metastasis.This notable study displays a delicate loop between the nervous system and cancer and,more importantly,amplifies the conception of apoptosis-induced metastasis.Over the past years,a mass of breakthrough studies have proven the pivotal role of the nervous system in tumorigenesis and cancer progression thereby contributing to the creation of a new disciplinecancer neuroscience[1].Hanahan and Monje discussed in detail the interactions between the nervous system and tumors based on the theoretical framework of the cancer hallmarks,focused on nerve-mediated proliferation,angiogenesis,immune evasion,cell death resistance,and metastasis[2].展开更多
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 g...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.展开更多
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 Walle...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.展开更多
Objective The present study evaluated the effects of deep acupuncture at Weizhong acupoint(BL40)on bladder function and brain activity in a rat model of overactive bladder(OAB),and investigated the possible mechanisms...Objective The present study evaluated the effects of deep acupuncture at Weizhong acupoint(BL40)on bladder function and brain activity in a rat model of overactive bladder(OAB),and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture.Methods Adult female Sprague-Dawley rats were randomly divided into six groups,comprising a control group,model group,group treated with deep acupuncture at BL40,group treated with shallow acupuncture at BL40,group treated with acupuncture at non-acupoint next to BL40,and group treated with acupuncture at Xuanzhong(GB39).Urodynamic evaluation was used to observe the urination,and functional magnetic resonance imaging was used to observe the brain activation.The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay,and the mechanism was verified by stabilizing mast cells(MCs)or blocking tibial nerve.Results Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex(M1),periaquaductal gray matter(PAG),and pontine micturition center(PMC).It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC.Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes.Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine,substance P,and histamine in the tissues around BL40.Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats.Conclusion Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve,thereby regulating the activation of the brain area that controls the lower urinary tract.展开更多
Heterotopic ossification(HO)is a pathological process that commonly arises following severe polytrauma,characterized by the anomalous differentiation of mesenchymal progenitor cells and resulting in the formation of e...Heterotopic ossification(HO)is a pathological process that commonly arises following severe polytrauma,characterized by the anomalous differentiation of mesenchymal progenitor cells and resulting in the formation of ectopic bone in non-skeletal tissues.This abnormal bone growth contributes to pain and reduced mobility,especially when adjacent to a joint.Our prior observations suggested an essential role of NGF(Nerve Growth Factor)-responsive TrkA(Tropomyosin Receptor Kinase A)-expressing peripheral nerves in regulating abnormal osteochondral differentiation following tendon injury.Here,we utilized a recently developed mouse model of hip arthroplasty-induced HO to further validate the role of peripheral nerve regulation of traumatic HO.Nerve ingrowth was either modulated using a knockin transgenic animals with point mutation in TrkA,or local treatment with an FDA-approved formulation of long acting Bupivacaine which prevents peripheral nerve growth.Results demonstrate exuberant sensory and sympathetic nerve growth within the peri-articular HO site,and that both methods to reduce local innervation significantly reduced heterotopic bone formation.TrkA inhibition led to a 34%reduction in bone volume,while bupivacaine treatment resulted in a 50%decrease.Mechanistically,alterations in TGFβand FGF signaling activation accompanied both methods of local denervation,and a shift in macrophages from M1 to M2 phenotypes was observed.In sum,these studies reinforce the observations that peripheral nerves play a role in the etiopathogenesis of HO,and that targeting local nerves represents a potential therapeutic approach for disease prevention.展开更多
Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside a...Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.展开更多
BACKGROUND The gold standard of care for patients with severe peripheral nerve injury is autologous nerve grafting;however,autologous nerve grafts are usually limited for patients because of the limited number of auto...BACKGROUND The gold standard of care for patients with severe peripheral nerve injury is autologous nerve grafting;however,autologous nerve grafts are usually limited for patients because of the limited number of autologous nerve sources and the loss of neurosensory sensation in the donor area,whereas allogeneic or xenografts are even more limited by immune rejection.Tissue-engineered peripheral nerve scaffolds,with the morphology and structure of natural nerves and complex biological signals,hold the most promise as ideal peripheral nerve“replacements”.AIM To prepare allogenic peripheral nerve scaffolds using a low-toxicity decellularization method,and use human umbilical cord mesenchymal stem cells(hUCMSCs)as seed cells to cultivate scaffold-cell complexes for the repair of injured peripheral nerves.METHODS After obtaining sciatic nerves from New Zealand rabbits,an optimal acellular scaffold preparation scheme was established by mechanical separation,varying lyophilization cycles,and trypsin and DNase digestion at different times.The scaffolds were evaluated by hematoxylin and eosin(HE)and luxol fast blue(LFB)staining.The maximum load,durability,and elastic modulus of the acellular scaffolds were assessed using a universal material testing machine.The acellular scaffolds were implanted into the dorsal erector spinae muscle of SD rats and the scaffold degradation and systemic inflammatory reactions were observed at 3 days,1 week,3 weeks,and 6 weeks following surgery to determine the histocompatibility between xenografts.The effect of acellular scaffold extracts on fibroblast proliferation was assessed using an MTT assay to measure the cytotoxicity of the scaffold residual reagents.In addition,the umbilical cord from cesarean section fetuses was collected,and the Wharton’s jelly(WJ)was separated into culture cells and confirm the osteogenic and adipogenic differentiation of mesenchymal stem cells(MSCs)and hUC-MSCs.The cultured cells were induced to differentiate into Schwann cells by the antioxidant-growth factor induction method,and the differentiated cells and the myelinogenic properties were identified.RESULTS The experiments effectively decellularized the sciatic nerve of the New Zealand rabbits.After comparing the completed acellular scaffolds among the groups,the optimal decellularization preparation steps were established as follows:Mechanical separation of the epineurium,two cycles of lyophilization-rewarming,trypsin digestion for 5 hours,and DNase digestion for 10 hours.After HE staining,no residual nuclear components were evident on the scaffold,whereas the extracellular matrix remained intact.LFB staining showed a significant decrease in myelin sheath composition of the scaffold compared with that before preparation.Biomechanical testing revealed that the maximum tensile strength,elastic modulus,and durability of the acellular scaffold were reduced compared with normal peripheral nerves.Based on the histocompatibility test,the immune response of the recipient SD rats to the scaffold New Zealand rabbits began to decline3 weeks following surgery,and there was no significant rejection after 6 weeks.The MTT assay revealed that the acellular reagent extract had no obvious effects on cell proliferation.The cells were successfully isolated,cultured,and passaged from human umbilical cord WJ by MSC medium,and their ability to differentiate into Schwann-like cells was demonstrated by morphological and immunohistochemical identification.The differentiated cells could also myelinate in vitro.CONCLUSION The acellular peripheral nerve scaffold with complete cell removal and intact matrix may be prepared by combining lyophilization and enzyme digestion.The resulting scaffold exhibited good histocompatibility and low cytotoxicity.In addition,hUC-MSCs have the potential to differentiate into Schwann-like cells with myelinogenic ability following in vitro induction.展开更多
Until now, nerve conduction has been described on the basis of equivalent circuit model and cable theory, both of which supposed closed electric circuits spreading inside and outside the axoplasm. With these conventio...Until now, nerve conduction has been described on the basis of equivalent circuit model and cable theory, both of which supposed closed electric circuits spreading inside and outside the axoplasm. With these conventional models, we can simulate the propagating pattern of action potential along the axonal membrane based on Ohm＇s law and Kirchhoff＇s law. However, we could not fully explain the different conductive patterns in unmyelinated and myelinated nerves with these theories. Also, whether we can really suppose closed electrical circuits in the actual site of the nerves or not has not been fully discussed yet. In this report, a recently introduced new theoretical model of nerve conduction based on electrostatic molecular interactions within the axoplasm will be reviewed. With this new approach, we can explain the different conductive patterns in unmyelinated and myelinated nerves. This new mathematical conductive model based on electrostatic compressional wave in the intracellular fluid may also be able to explain the signal integration in the neuronal cell body and the back-propagation mechanism from the axons to the dendrites. With this new mathematical nerve conduction model based on electrostatic molecular interactions within the intracellular fluid, we may be able to achieve an integrated explanation for the physiological phenomena taking place in the nervous system.展开更多
Accurate localization of cranial nerves and responsible blood vessels is important for diagnosing trigeminal neuralgia(TN)and hemifacial spasm(HFS).Manual delineation of the nerves and vessels on medical images is tim...Accurate localization of cranial nerves and responsible blood vessels is important for diagnosing trigeminal neuralgia(TN)and hemifacial spasm(HFS).Manual delineation of the nerves and vessels on medical images is time-consuming and labor-intensive.Due to the development of convolutional neural networks(CNNs),the performance of medical image segmentation has been improved.In this work,we investigate the plans for automated segmentation of cranial nerves and responsible vessels for TN and HFS,which has not been comprehensively studied before.Different inputs are given to the CNN to find the best training configuration of segmenting trigeminal nerves,facial nerves,responsible vessels and brainstem,including the image modality and the number of segmentation targets.According to multiple experiments with seven training plans,we suggest training with the combination of three-dimensional fast imaging employing steady-state acquisition(3D-FIESTA)and three-dimensional time-of-flight magnetic resonance angiography(3DTOF-MRA),and separate segmentation of cranial nerves and vessels.展开更多
OBJECTIVE:To observe the clinical efficacy of acupuncture along fascia,meridians,and nerves combined with ultrasound-guided nerve blockage in the treatment of postherpetic neuralgia.METHODS:A total of 61 outpatients w...OBJECTIVE:To observe the clinical efficacy of acupuncture along fascia,meridians,and nerves combined with ultrasound-guided nerve blockage in the treatment of postherpetic neuralgia.METHODS:A total of 61 outpatients with post-chest and back herpes zoster neuralgia were recruited in the Department of Pain at the Xiyuan Hospital,China Academy of Chinese Medical Sciences from May 2019 to June 2021.They were randomly divided into two groups.Thirty-one patients in the control group were treated with ultrasound-guided thoracic paravertebral nerve block(PVB)alone,one patient declined to continue during treatment(n=30),and thirty patients in the observation group received the acupuncture along the fascia,meridians,and nerves combined with ultrasound-guided PVB treatment(n=30).Both control and observation group received treatment weekly for 4 weeks.The medical history data such as age,sex,presence or absence of comorbidities and disease course were analyzed.The visual analog scale(VAS)score was used to assess the pain degree of two groups at T0(before treatment),T1(1-time treatment ended),T2(2 times treatment ended),T3(3 times treatment ended),and T4(4 times treatment ended).The sleep state was examined by Pittsburgh Sleep Quality Index(PSQI)before and after the study.RESULTS:There was no significant difference in general conditions between the control group and the observation group(P>0.05).The VAS score in both control and observation group was decreased in a time-dependent manner after 1-4 weeks of treatment.There were no significant differences in VAS scores between the two groups after 1 or 2 weeks of treatment(P>0.05).After 3 and 4 weeks of treatment,the VAS score was significantly decreased in the observation group compared with that in the control group(P<0.001).In addition,the reduction in VAS score(after treatment-before treatment)between the two groups was statistically significant[D value:-1.53,95%CI(-2.32,0.74),P<0.001].Furthermore,the sleep state of patients in both groups markedly improved and much obvious in the observation group than that in the control group(P<0.05).CONCLUSION:These results suggest that a combination of acupuncture along fascia,meridians,and nerves with ultrasound-guided PVB treatment is more effective than ultrasound-guided PVB treatment alone.展开更多
A low-power IC for function electrical stimulation （FES） of nerves is designed for an implantable system and fabricated in CSMC＇s 0.6μm CMOS technology. The IC can be used for stimulating animals＇ spinal nerve bu...A low-power IC for function electrical stimulation （FES） of nerves is designed for an implantable system and fabricated in CSMC＇s 0.6μm CMOS technology. The IC can be used for stimulating animals＇ spinal nerve bundles and other nerves connected with a cuff type electrode. It consists of a pre-amplifier,a main amplifier,and an output stage. According to the neural signal spectrum,the bandwidth of the FES signal generator circuit is defined from 1Hz to 400kHz. The gain of the circuit is about 66dB with an output impedance of 900. The 1C can function under a single supply voltage of 3-5V. A rail-to-rail output stage helps to use the coupled power efficiently. The measured time domain performance shows that the bandwidth and the gain of the IC agree with the design. The power consumption is lower than 6mW.展开更多
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
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
The neurovascular bundle of the prostate and cavernosal nerves have been used to describe the same structure ever since the publication of the first studies on the neuroanatomy of the lower urogenital tract of men, st...The neurovascular bundle of the prostate and cavernosal nerves have been used to describe the same structure ever since the publication of the first studies on the neuroanatomy of the lower urogenital tract of men, studies that were prompted by postoperative complications arising from radical prostatectomy. In urological surgery every effort is made to preserve or restore the neurovascular bundle of the prostate to avoid erectile dysfunction （ED）. However, the postoperative potency rates are yet to be satisfactory despite all advancements in radical prostatectomy technique. As the technology associated with urological surgery develops and topographical studies on neuroanatomy are cultivated, new observations seriously challenge the classical teachings on the topography of the neurovascular bundle of the prostate and the cavernosal nerves. The present review revisits the classical and most recent data on the topographical anatomy of the neurovascular bundle of the prostate prostatectomy techniques.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
Both brain injury and tacrolimus have been reported to promote the regeneration of injured peripheral nerves. In this study, before transection of rat sciatic nerve, moderate brain contusion was（or was not） induced....Both brain injury and tacrolimus have been reported to promote the regeneration of injured peripheral nerves. In this study, before transection of rat sciatic nerve, moderate brain contusion was（or was not） induced. After sciatic nerve injury, tacrolimus, an immunosuppressant, was（or was not） intraperitoneally administered. At 4, 8 and 12 weeks after surgery, Masson＇s trichrome, hematoxylin-eosin, and toluidine blue staining results revealed that brain injury or tacrolimus alone or their combination alleviated gastrocnemius muscle atrophy and sciatic nerve fiber impairment on the experimental side, simultaneously improved sciatic nerve function, and increased gastrocnemius muscle wet weight on the experimental side. At 8 and 12 weeks after surgery, brain injury induction and/or tacrolimus treatment increased action potential amplitude in the sciatic nerve trunk. Horseradish peroxidase retrograde tracing revealed that the number of horseradish peroxidase-positive neurons in the anterior horn of the spinal cord was greatly increased. Brain injury in combination with tacrolimus exhibited better effects on repair of injured peripheral nerves than brain injury or tacrolimus alone. This result suggests that brain injury in combination with tacrolimus promotes repair of peripheral nerve injury.展开更多
AIMTo examine the occurrence of commonly known clinical signs of keratoconus (KC), i.e. Fleischer ring, prominent corneal nerves and thinning, among unaffected family members of KC patients and healthy control individ...AIMTo examine the occurrence of commonly known clinical signs of keratoconus (KC), i.e. Fleischer ring, prominent corneal nerves and thinning, among unaffected family members of KC patients and healthy control individuals.METHODSData of both eyes of 117 relatives of KC patients having no manifest disease based on videokeratography indices (KC relatives), and 142 controls were used for Pearson correlation and t-test statistics. Correlation of Fleischer ring, prominent corneal nerves and central pachymetry data were tested with each other and with videokeratography indices (KSI, KISA, 3 and 6 mm Fourier asymmetry, and I-S).RESULTSA moderate correlation was found between Fleischer ring and all examined topographical indices. Most important correlation was present with 6 mm Fourier asymmetry, and corneal pachymetry (r=0.272, P<0.001; r=-0.234, P=0.027, respectively). Similar correlations were found with prominent corneal nerves (r=0.234, P<0.001 for 6 mm Fourier asymmetry and r=-0.235, P=0.0265 for pachymetry). KC family members who exhibited Fleischer ring or prominent nerves had thinner and more asymmetric corneas than those without Fleischer ring or prominent corneal nerves (P<0.05 for pachymetry and topographic indices with t-test and Mann-Whitney rank sum test). Though rarely, Fleischer ring and prominent corneal nerves occurred among normal controls, indicating the existence of forme fruste cases in the normal population. Control subjects, who had corneal Fleischer ring or prominent nerves had corneas more similar to KC than other controls (t-test: increased KSI and KISA, P=0.048 and 0.012, respectively).CONCLUSIONIn KC family members and healthy individuals, Fleischer ring and prominent corneal nerves are associated with features of KC and may suggest a possibility of forme fruste KC. Searching for the possible presence of Fleischer ring or prominent nerves on the cornea may help in the decision whether or not to diagnose subclinical KC in a borderline case.展开更多
Two hundred cates of nasopharyngeal carcinoma (NPC) admitted to this department from Feb. 1985 to May. 1988 were analysed according to the CT scanning and clinical findings of the primary lesions prior to radiotherapy...Two hundred cates of nasopharyngeal carcinoma (NPC) admitted to this department from Feb. 1985 to May. 1988 were analysed according to the CT scanning and clinical findings of the primary lesions prior to radiotherapy. The results showed that involvement of parapharyngeal space was very common in NPC, about 80% (160/200 cases) ; particularly unilateral or bilateral retro-styloid spaces, about 69.5% (139/200 cases). It was proposed that patients with NPC had a high Incidence of ipsilateral cervical node metastasis. Contralateral cervical node metastasis was rare. The development of cervical node metastasto in NPC has two modes: one Is direct Infiltration of the retro-stylold space by the lesion; the other Is along the nasopharyngeal lymphatic rete. The data also showed that patients with NPC who presented symptoms of Ⅸ- Ⅲ cranial nerve paralyses always had ipsilateral or bilateral retro- styloid space Infiltrations.展开更多
Vascularization of acellular nerves has been shown to contribute to nerve bridging.In this study,we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the...Vascularization of acellular nerves has been shown to contribute to nerve bridging.In this study,we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves.The rat nerve defects were treated with acellular nerve grafting（control group） alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein（experimental group）.As shown through two-dimensional imaging,the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation,and gradually covered the entire graft at day 21.The vascular density,vascular area,and the velocity of revascularization in the experimental group were all higher than those in the control group.These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves.展开更多
基金National Nature Science Foundation of China 82471000(to K.J.)National Nature Science Foundation of China 82170978(to K.J.)+1 种基金National Nature Science Foundation of China 82325012(to L.N.N.)National Key Research and Development Program 2023YFC2509100(to K.J.)。
文摘Temporomandibular joint osteoarthritis(TMJ-OA)is a common disease often accompanied by pain,seriously affecting physical and mental health of patients.Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia,while the specific mechanism mediating pain remains unclear.To investigate the underlying mechanism of TMJ-OA pain,an abnormal joint loading model was used to induce TMJ-OA pain.We found that during the development of TMJ-OA,the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves.Furthermore,these two types of nerves are spatially closely associated.Additionally,it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice,whereas blocking these signals effectively alleviates pain.In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons.Moreover,we also discovered that through releasing norepinephrine,regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators.This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA.It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves,providing a potential target for treating TMJ-OA pain.
文摘Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-derived substance P could induce apoptosis in breast cancer cells that overexpressed tachykinin receptors.Single-stranded RNAs(ssRNAs)leaking from dying cells subsequently interact with toll-like receptor 7(TLR7)on other cancer cells and finally promoted metastasis.This notable study displays a delicate loop between the nervous system and cancer and,more importantly,amplifies the conception of apoptosis-induced metastasis.Over the past years,a mass of breakthrough studies have proven the pivotal role of the nervous system in tumorigenesis and cancer progression thereby contributing to the creation of a new disciplinecancer neuroscience[1].Hanahan and Monje discussed in detail the interactions between the nervous system and tumors based on the theoretical framework of the cancer hallmarks,focused on nerve-mediated proliferation,angiogenesis,immune evasion,cell death resistance,and metastasis[2].
基金supported by the Department of Defense AFIRMⅢW81XWH-20-2-0029 grant subcontractLone Star Paralysis gift,UT POC19-1774-13 grant+1 种基金Neuraptive Therapeutics Inc.26-7724-56 grantNational Institutes of Health R01-NS128086(all to GDB)。
文摘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.
基金supported by DOD AFIRMⅢW81XWH-20-2-0029 subcontract,UT POC19-1774-13Neuraptive Therapeutics Inc.26-7724-56+1 种基金NIH R01-NS128086 grantsLone Star Paralysis gift(to GDB)。
文摘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.
基金supported by grants from the Shanghai Science and Technology Commission(No.21ZR1461000)Shanghai Municipal Health Commission(No.ZY[2021–2023]−0204).
文摘Objective The present study evaluated the effects of deep acupuncture at Weizhong acupoint(BL40)on bladder function and brain activity in a rat model of overactive bladder(OAB),and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture.Methods Adult female Sprague-Dawley rats were randomly divided into six groups,comprising a control group,model group,group treated with deep acupuncture at BL40,group treated with shallow acupuncture at BL40,group treated with acupuncture at non-acupoint next to BL40,and group treated with acupuncture at Xuanzhong(GB39).Urodynamic evaluation was used to observe the urination,and functional magnetic resonance imaging was used to observe the brain activation.The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay,and the mechanism was verified by stabilizing mast cells(MCs)or blocking tibial nerve.Results Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex(M1),periaquaductal gray matter(PAG),and pontine micturition center(PMC).It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC.Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes.Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine,substance P,and histamine in the tissues around BL40.Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats.Conclusion Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve,thereby regulating the activation of the brain area that controls the lower urinary tract.
基金supported by NIH/NIAMS (P01 AG066603,R01 AR079171,R01 AR079171-07S1,R21AR078919)NIH/NIDCR (R01 DE031488,R01 DE031028)+4 种基金Alex’s Lemonade Stand Foundation (22-26743)American Cancer Society (DBG-23-1155131-01-IBCD)the Maryland Stem Cell Research Foundation (2021-MSCRFD-5641)Department of Defense (USAMRAA HT9425-24-1-0051)supported by NIH/NIAMS (R01 AR079171-07,R01 AR079171-07S1)。
文摘Heterotopic ossification(HO)is a pathological process that commonly arises following severe polytrauma,characterized by the anomalous differentiation of mesenchymal progenitor cells and resulting in the formation of ectopic bone in non-skeletal tissues.This abnormal bone growth contributes to pain and reduced mobility,especially when adjacent to a joint.Our prior observations suggested an essential role of NGF(Nerve Growth Factor)-responsive TrkA(Tropomyosin Receptor Kinase A)-expressing peripheral nerves in regulating abnormal osteochondral differentiation following tendon injury.Here,we utilized a recently developed mouse model of hip arthroplasty-induced HO to further validate the role of peripheral nerve regulation of traumatic HO.Nerve ingrowth was either modulated using a knockin transgenic animals with point mutation in TrkA,or local treatment with an FDA-approved formulation of long acting Bupivacaine which prevents peripheral nerve growth.Results demonstrate exuberant sensory and sympathetic nerve growth within the peri-articular HO site,and that both methods to reduce local innervation significantly reduced heterotopic bone formation.TrkA inhibition led to a 34%reduction in bone volume,while bupivacaine treatment resulted in a 50%decrease.Mechanistically,alterations in TGFβand FGF signaling activation accompanied both methods of local denervation,and a shift in macrophages from M1 to M2 phenotypes was observed.In sum,these studies reinforce the observations that peripheral nerves play a role in the etiopathogenesis of HO,and that targeting local nerves represents a potential therapeutic approach for disease prevention.
基金supported by Fondo para la Investigación Cientifica y Tecnológica(FONCy T),Argentina,grant#PICT 2015-2473(to PHHL)supported by grants from National Institute of Health/National Institute of Neurological Disorders and Stroke(NIH/NINDS,USA)(NS121621)+2 种基金Department of Defense,USA(Do D-CL1)(PR200530)partially financed with a fellowship for Research in Medicine from Fundación Florencio Fiorinisupported with a PhD fellowship from CONICET。
文摘Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.
文摘BACKGROUND The gold standard of care for patients with severe peripheral nerve injury is autologous nerve grafting;however,autologous nerve grafts are usually limited for patients because of the limited number of autologous nerve sources and the loss of neurosensory sensation in the donor area,whereas allogeneic or xenografts are even more limited by immune rejection.Tissue-engineered peripheral nerve scaffolds,with the morphology and structure of natural nerves and complex biological signals,hold the most promise as ideal peripheral nerve“replacements”.AIM To prepare allogenic peripheral nerve scaffolds using a low-toxicity decellularization method,and use human umbilical cord mesenchymal stem cells(hUCMSCs)as seed cells to cultivate scaffold-cell complexes for the repair of injured peripheral nerves.METHODS After obtaining sciatic nerves from New Zealand rabbits,an optimal acellular scaffold preparation scheme was established by mechanical separation,varying lyophilization cycles,and trypsin and DNase digestion at different times.The scaffolds were evaluated by hematoxylin and eosin(HE)and luxol fast blue(LFB)staining.The maximum load,durability,and elastic modulus of the acellular scaffolds were assessed using a universal material testing machine.The acellular scaffolds were implanted into the dorsal erector spinae muscle of SD rats and the scaffold degradation and systemic inflammatory reactions were observed at 3 days,1 week,3 weeks,and 6 weeks following surgery to determine the histocompatibility between xenografts.The effect of acellular scaffold extracts on fibroblast proliferation was assessed using an MTT assay to measure the cytotoxicity of the scaffold residual reagents.In addition,the umbilical cord from cesarean section fetuses was collected,and the Wharton’s jelly(WJ)was separated into culture cells and confirm the osteogenic and adipogenic differentiation of mesenchymal stem cells(MSCs)and hUC-MSCs.The cultured cells were induced to differentiate into Schwann cells by the antioxidant-growth factor induction method,and the differentiated cells and the myelinogenic properties were identified.RESULTS The experiments effectively decellularized the sciatic nerve of the New Zealand rabbits.After comparing the completed acellular scaffolds among the groups,the optimal decellularization preparation steps were established as follows:Mechanical separation of the epineurium,two cycles of lyophilization-rewarming,trypsin digestion for 5 hours,and DNase digestion for 10 hours.After HE staining,no residual nuclear components were evident on the scaffold,whereas the extracellular matrix remained intact.LFB staining showed a significant decrease in myelin sheath composition of the scaffold compared with that before preparation.Biomechanical testing revealed that the maximum tensile strength,elastic modulus,and durability of the acellular scaffold were reduced compared with normal peripheral nerves.Based on the histocompatibility test,the immune response of the recipient SD rats to the scaffold New Zealand rabbits began to decline3 weeks following surgery,and there was no significant rejection after 6 weeks.The MTT assay revealed that the acellular reagent extract had no obvious effects on cell proliferation.The cells were successfully isolated,cultured,and passaged from human umbilical cord WJ by MSC medium,and their ability to differentiate into Schwann-like cells was demonstrated by morphological and immunohistochemical identification.The differentiated cells could also myelinate in vitro.CONCLUSION The acellular peripheral nerve scaffold with complete cell removal and intact matrix may be prepared by combining lyophilization and enzyme digestion.The resulting scaffold exhibited good histocompatibility and low cytotoxicity.In addition,hUC-MSCs have the potential to differentiate into Schwann-like cells with myelinogenic ability following in vitro induction.
文摘Until now, nerve conduction has been described on the basis of equivalent circuit model and cable theory, both of which supposed closed electric circuits spreading inside and outside the axoplasm. With these conventional models, we can simulate the propagating pattern of action potential along the axonal membrane based on Ohm＇s law and Kirchhoff＇s law. However, we could not fully explain the different conductive patterns in unmyelinated and myelinated nerves with these theories. Also, whether we can really suppose closed electrical circuits in the actual site of the nerves or not has not been fully discussed yet. In this report, a recently introduced new theoretical model of nerve conduction based on electrostatic molecular interactions within the axoplasm will be reviewed. With this new approach, we can explain the different conductive patterns in unmyelinated and myelinated nerves. This new mathematical conductive model based on electrostatic compressional wave in the intracellular fluid may also be able to explain the signal integration in the neuronal cell body and the back-propagation mechanism from the axons to the dendrites. With this new mathematical nerve conduction model based on electrostatic molecular interactions within the intracellular fluid, we may be able to achieve an integrated explanation for the physiological phenomena taking place in the nervous system.
文摘Accurate localization of cranial nerves and responsible blood vessels is important for diagnosing trigeminal neuralgia(TN)and hemifacial spasm(HFS).Manual delineation of the nerves and vessels on medical images is time-consuming and labor-intensive.Due to the development of convolutional neural networks(CNNs),the performance of medical image segmentation has been improved.In this work,we investigate the plans for automated segmentation of cranial nerves and responsible vessels for TN and HFS,which has not been comprehensively studied before.Different inputs are given to the CNN to find the best training configuration of segmenting trigeminal nerves,facial nerves,responsible vessels and brainstem,including the image modality and the number of segmentation targets.According to multiple experiments with seven training plans,we suggest training with the combination of three-dimensional fast imaging employing steady-state acquisition(3D-FIESTA)and three-dimensional time-of-flight magnetic resonance angiography(3DTOF-MRA),and separate segmentation of cranial nerves and vessels.
文摘OBJECTIVE:To observe the clinical efficacy of acupuncture along fascia,meridians,and nerves combined with ultrasound-guided nerve blockage in the treatment of postherpetic neuralgia.METHODS:A total of 61 outpatients with post-chest and back herpes zoster neuralgia were recruited in the Department of Pain at the Xiyuan Hospital,China Academy of Chinese Medical Sciences from May 2019 to June 2021.They were randomly divided into two groups.Thirty-one patients in the control group were treated with ultrasound-guided thoracic paravertebral nerve block(PVB)alone,one patient declined to continue during treatment(n=30),and thirty patients in the observation group received the acupuncture along the fascia,meridians,and nerves combined with ultrasound-guided PVB treatment(n=30).Both control and observation group received treatment weekly for 4 weeks.The medical history data such as age,sex,presence or absence of comorbidities and disease course were analyzed.The visual analog scale(VAS)score was used to assess the pain degree of two groups at T0(before treatment),T1(1-time treatment ended),T2(2 times treatment ended),T3(3 times treatment ended),and T4(4 times treatment ended).The sleep state was examined by Pittsburgh Sleep Quality Index(PSQI)before and after the study.RESULTS:There was no significant difference in general conditions between the control group and the observation group(P>0.05).The VAS score in both control and observation group was decreased in a time-dependent manner after 1-4 weeks of treatment.There were no significant differences in VAS scores between the two groups after 1 or 2 weeks of treatment(P>0.05).After 3 and 4 weeks of treatment,the VAS score was significantly decreased in the observation group compared with that in the control group(P<0.001).In addition,the reduction in VAS score(after treatment-before treatment)between the two groups was statistically significant[D value:-1.53,95%CI(-2.32,0.74),P<0.001].Furthermore,the sleep state of patients in both groups markedly improved and much obvious in the observation group than that in the control group(P<0.05).CONCLUSION:These results suggest that a combination of acupuncture along fascia,meridians,and nerves with ultrasound-guided PVB treatment is more effective than ultrasound-guided PVB treatment alone.
文摘A low-power IC for function electrical stimulation （FES） of nerves is designed for an implantable system and fabricated in CSMC＇s 0.6μm CMOS technology. The IC can be used for stimulating animals＇ spinal nerve bundles and other nerves connected with a cuff type electrode. It consists of a pre-amplifier,a main amplifier,and an output stage. According to the neural signal spectrum,the bandwidth of the FES signal generator circuit is defined from 1Hz to 400kHz. The gain of the circuit is about 66dB with an output impedance of 900. The 1C can function under a single supply voltage of 3-5V. A rail-to-rail output stage helps to use the coupled power efficiently. The measured time domain performance shows that the bandwidth and the gain of the IC agree with the design. The power consumption is lower than 6mW.
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 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.
文摘The neurovascular bundle of the prostate and cavernosal nerves have been used to describe the same structure ever since the publication of the first studies on the neuroanatomy of the lower urogenital tract of men, studies that were prompted by postoperative complications arising from radical prostatectomy. In urological surgery every effort is made to preserve or restore the neurovascular bundle of the prostate to avoid erectile dysfunction （ED）. However, the postoperative potency rates are yet to be satisfactory despite all advancements in radical prostatectomy technique. As the technology associated with urological surgery develops and topographical studies on neuroanatomy are cultivated, new observations seriously challenge the classical teachings on the topography of the neurovascular bundle of the prostate and the cavernosal nerves. The present review revisits the classical and most recent data on the topographical anatomy of the neurovascular bundle of the prostate prostatectomy techniques.
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supported by a grant from the Mandatory Project of Health Department of Hebei Province of China,No.20130027a grant from the Mandatory Project of Science and Technology Department of Hebei Province of China,No.142777105Da grant from Science and Technology Bureau of Chengde City of Hebei Province of China,No.20123128
文摘Both brain injury and tacrolimus have been reported to promote the regeneration of injured peripheral nerves. In this study, before transection of rat sciatic nerve, moderate brain contusion was（or was not） induced. After sciatic nerve injury, tacrolimus, an immunosuppressant, was（or was not） intraperitoneally administered. At 4, 8 and 12 weeks after surgery, Masson＇s trichrome, hematoxylin-eosin, and toluidine blue staining results revealed that brain injury or tacrolimus alone or their combination alleviated gastrocnemius muscle atrophy and sciatic nerve fiber impairment on the experimental side, simultaneously improved sciatic nerve function, and increased gastrocnemius muscle wet weight on the experimental side. At 8 and 12 weeks after surgery, brain injury induction and/or tacrolimus treatment increased action potential amplitude in the sciatic nerve trunk. Horseradish peroxidase retrograde tracing revealed that the number of horseradish peroxidase-positive neurons in the anterior horn of the spinal cord was greatly increased. Brain injury in combination with tacrolimus exhibited better effects on repair of injured peripheral nerves than brain injury or tacrolimus alone. This result suggests that brain injury in combination with tacrolimus promotes repair of peripheral nerve injury.
基金Supported by Hungarian National Research Fund Grants OTKA F046321 and TAMOP-4.2.1/B-09/1/KONV-2010-0007
文摘AIMTo examine the occurrence of commonly known clinical signs of keratoconus (KC), i.e. Fleischer ring, prominent corneal nerves and thinning, among unaffected family members of KC patients and healthy control individuals.METHODSData of both eyes of 117 relatives of KC patients having no manifest disease based on videokeratography indices (KC relatives), and 142 controls were used for Pearson correlation and t-test statistics. Correlation of Fleischer ring, prominent corneal nerves and central pachymetry data were tested with each other and with videokeratography indices (KSI, KISA, 3 and 6 mm Fourier asymmetry, and I-S).RESULTSA moderate correlation was found between Fleischer ring and all examined topographical indices. Most important correlation was present with 6 mm Fourier asymmetry, and corneal pachymetry (r=0.272, P<0.001; r=-0.234, P=0.027, respectively). Similar correlations were found with prominent corneal nerves (r=0.234, P<0.001 for 6 mm Fourier asymmetry and r=-0.235, P=0.0265 for pachymetry). KC family members who exhibited Fleischer ring or prominent nerves had thinner and more asymmetric corneas than those without Fleischer ring or prominent corneal nerves (P<0.05 for pachymetry and topographic indices with t-test and Mann-Whitney rank sum test). Though rarely, Fleischer ring and prominent corneal nerves occurred among normal controls, indicating the existence of forme fruste cases in the normal population. Control subjects, who had corneal Fleischer ring or prominent nerves had corneas more similar to KC than other controls (t-test: increased KSI and KISA, P=0.048 and 0.012, respectively).CONCLUSIONIn KC family members and healthy individuals, Fleischer ring and prominent corneal nerves are associated with features of KC and may suggest a possibility of forme fruste KC. Searching for the possible presence of Fleischer ring or prominent nerves on the cornea may help in the decision whether or not to diagnose subclinical KC in a borderline case.
文摘Two hundred cates of nasopharyngeal carcinoma (NPC) admitted to this department from Feb. 1985 to May. 1988 were analysed according to the CT scanning and clinical findings of the primary lesions prior to radiotherapy. The results showed that involvement of parapharyngeal space was very common in NPC, about 80% (160/200 cases) ; particularly unilateral or bilateral retro-styloid spaces, about 69.5% (139/200 cases). It was proposed that patients with NPC had a high Incidence of ipsilateral cervical node metastasis. Contralateral cervical node metastasis was rare. The development of cervical node metastasto in NPC has two modes: one Is direct Infiltration of the retro-stylold space by the lesion; the other Is along the nasopharyngeal lymphatic rete. The data also showed that patients with NPC who presented symptoms of Ⅸ- Ⅲ cranial nerve paralyses always had ipsilateral or bilateral retro- styloid space Infiltrations.
基金supported by the Specialized Research Fund for Science and Technology Plan of Guangdong Province in China,No.201313060300007the National High-Technology Research and Development Program of China(863 Program),No.2012AA020507+2 种基金the National Basic Research Program of China(973 Program),No.2014CB542201the Doctoral Program of Higher Education of China,No.20120171120075Doctoral Start-up Project of the Natural Science Foundation of Guangdong Province in China,No.S201204006336 and 1045100890100590
文摘Vascularization of acellular nerves has been shown to contribute to nerve bridging.In this study,we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves.The rat nerve defects were treated with acellular nerve grafting（control group） alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein（experimental group）.As shown through two-dimensional imaging,the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation,and gradually covered the entire graft at day 21.The vascular density,vascular area,and the velocity of revascularization in the experimental group were all higher than those in the control group.These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves.
