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
FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways ...FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.展开更多
End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve.It involves suturing the distal stump of the disconnected nerve(recipient nerve) to the side of the intimate adjacent ne...End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve.It involves suturing the distal stump of the disconnected nerve(recipient nerve) to the side of the intimate adjacent nerve(donor nerve).However,the motor-sensory specificity after end-to-side neurorrhaphy remains unclear.This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy.Thirty rats were randomized into three groups:(1) end-to-side neurorrhaphy using the ulnar nerve(mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve;(2) the sham group:ulnar nerve and cutaneous antebrachii medialis nerve were just exposed;and(3) the transected nerve group:cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied.At 5 months,acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group,and none of the myelinated axons were stained in either the sham or transected nerve groups.Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%.In contrast,no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment.These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.展开更多
Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming...Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013:221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.展开更多
The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peri...The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A m RNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration.展开更多
Emerging evidence supports that the stress response to peripheral nerve injury extends beyond the injured neuron,with alterations in associated transcription factors detected both locally and remote to the lesion.Stre...Emerging evidence supports that the stress response to peripheral nerve injury extends beyond the injured neuron,with alterations in associated transcription factors detected both locally and remote to the lesion.Stress-induced nuclear translocation of the transcription factor forkhead class box O3a(FOXO3a)was initially linked to activation of apoptotic genes in many neuronal subtypes.However,a more complex role of FOXO3a has been suggested in the injury response of sensory neurons,with the injured neuron expressing less FOXO3a.To elucidate this response and test whether non-injured sensory neurons also alter FOXO3a expression,the temporal impact of chronic unilateral L4–6 spinal nerve transection on FOXO3a expression and nuclear localization in adult rat dorsal root ganglion neurons ipsilateral,contralateral or remote to injury relative to na?ve controls was examined.In na?ve neurons,high cytoplasmic and nuclear levels of FOXO3a colocalized with calcitonin gene related peptide,a marker of the nociceptive subpopulation.One hour post-injury,an acute increase in nuclear FOXO3a in small size injured neurons occurred followed by a significant decrease after 1,2 and 4 days,with levels increasing toward pre-injury levels by 1 week post-injury.A more robust biphasic response to the injury was observed in uninjured neurons contralateral to and those remote to injury.Nuclear levels of FOXO3a peaked at 1 day,decreased by 4 days,then increased by 1 week post-injury,a response mirrored in C4 dorsal root ganglion neurons remote to injury.This altered expression contralateral and remote to injury supports that spinal nerve damage has broader systemic impacts,a response we recently reported for another stress transcription factor,Luman/CREB3.The early decreased expression and nuclear localization of FOXO3a in the injured neuron implicate these changes in the cell body response to injury that may be protective.Finally,the broader systemic changes support the existence of stress/injury-induced humeral factor(s)influencing transcriptional and potentially behavioral changes in uninjured dorsal root ganglion neurons.Approval to conduct this study was obtained from the University of Saskatchewan Animal Research Ethics Board(protocol#19920164).展开更多
BACKGROUND: In recent years, surgeons have advocated root or trunk repair of avulsed nerve roots for overall recovery. However, donor nerves pose a major problem, because they do not contain adequate numbers of axons...BACKGROUND: In recent years, surgeons have advocated root or trunk repair of avulsed nerve roots for overall recovery. However, donor nerves pose a major problem, because they do not contain adequate numbers of axons. Moreover, the procedures lead to nerve deficits in the donor nerve following transplantation. OBJECTIVE: To observe whether axonal regeneration occurs by end-to-side neurorrhaphy in the peripheral nerve and spinal cord. DESIGN, TIME AND SETTING: A neuroanatomical, randomized, controlled, animal study was performed at Functional Anatomy Lab in Nagoya University School of Medicine from May 2002 to July 2003. MATERIALS: Fluorogold was purchased from Fluorochrome, LLC, USA. BX50 light microscope and fluorescent microscope were purchased from Olympus, Japan. METHODS: A total of 21 rats were randomly divided into three groups, and the posterior avulsion injury model (C6-8) of the brachial plexus was performed. In the ventral root graft group, the avulsed C7 ventral roots were reanastomosed to the small anterior lateral aspect window of the spinal cord via nerve grafts. In the dorsal root graft group, the C7 dorsal roots were reanastomosed at the small pia mater window of the posterior lateral aspect of the spinal cord via nerve grafts. In the control group, the avulsed nerve roots were not repaired. MAIN OUTCOME MEASURES: The nerve grafts were collected from the ventral and dorsal root graft groups, and the C7 proximal nerve end was collected from the control group. Acetylcholinesterase staining was performed on the tissue. Fluorogold retrograde tracing technique was applied to determine the origin of the regenerating axons. RESULTS: Results showed that acetylcholine-positive axons existed in nerve grafts of the ventral and dorsal root graft groups. However, axons were not found in the avulsed nerve roots of the control group. Fluorogold retrograde tracing confirmed the presence of fluorogold-containing neurons in the ventral and dorsal horn of the ventral and dorsal root graft groups. Fluorogold-positive neurons were not observed in the control group. CONCLUSION: End-to-side neurorrhaphy induced axonal regeneration from the spinal cord to the peripheral nervous system.展开更多
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...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.展开更多
In this study, we loaded human umbilical cord mesenchymal stem cells onto human amniotic membrane with epithelial cells to prepare nerve conduits, i.e., a relatively closed nerve regeneration chamber. After neurolysis...In this study, we loaded human umbilical cord mesenchymal stem cells onto human amniotic membrane with epithelial cells to prepare nerve conduits, i.e., a relatively closed nerve regeneration chamber. After neurolysis, the injured radial nerve was enwrapped with the prepared nerve conduit, which was fixed to the epineurium by sutures, with the cell on the inner surface of the conduit. Simultaneously, a 1.0 mL aliquot of human umbilical cord mesenchymal stem cell suspension was injected into the distal and proximal ends of the injured radial nerve with 1.0 cm intervals. A total of 1.75 x 107 cells were seeded on the amniotic membrane. In the control group, patients received only neurolysis. At 12 weeks after cell transplantation, more than 80% of patients exhibited obvious improvements in muscular strength, and touch and pain sensations. In contrast, these improvements were observed only in 55-65% of control patients. At 8 and 12 weeks, muscular electrophysiological function in the region dominated by the injured radial nerve was significantly better in the transplantation group than the control group. After cell transplantation, no immunological rejections were observed. These findings suggest that human umbilical cord mesenchymal stem cell-loaded amniotic membrane can be used for the repair of radial nerve injury.展开更多
Human periodontal ligament stem cells are easily accessible and can differentiate into Schwann cells. We hypothesized that human periodontal ligament stem cells can be used as an alternative source for the autologous ...Human periodontal ligament stem cells are easily accessible and can differentiate into Schwann cells. We hypothesized that human periodontal ligament stem cells can be used as an alternative source for the autologous Schwann cells in promoting the regeneration of injured peripheral nerve. To validate this hypothesis, human periodontal ligament stem cells (1 × 106) were injected into the crush-injured left mental nerve in rats. Simultaneously, autologous Schwann cells (1 × 106) and PBS were also injected as controls. Real-time reverse transcriptase polymerase chain reaction showed that at 5 days after injection, mRNA expression of low affinity nerve growth factor receptor was sig-nificantaly increased in the left trigeminal ganglion of rats with mental nerve injury. Sensory tests, histomorphometric evaluation and retrograde labeling demonstrated that at 2 and 4 weeks after in-jection, sensory function was significantly improved, the numbers of retrograde labeled sensory neurons and myelinated axons were significantly increased, and human periodontal ligament stem cells and autologous Schwann cells exhibited similar therapeutic effects. These findings suggest that transplantation of human periodontal ligament stem cells show a potential value in repair of mental nerve injury.展开更多
A new nerve matrix membrane derived from decellularized porcine nerves has been shown to retain the major extracellular matrix components, and to be effective in preventing adhesion between the nerve anastomosis sites...A new nerve matrix membrane derived from decellularized porcine nerves has been shown to retain the major extracellular matrix components, and to be effective in preventing adhesion between the nerve anastomosis sites and the surrounding tissues in a rat sciatic nerve transection model, thereby enhancing regeneration of the nerve. The effectiveness of the membrane may be attributed to its various bioactive components. In this prospective, randomized, single-blind, parallel-controlled multicenter clinical trial, we compared the safety and efficacy of the new nerve matrix membrane with a previously approved bovine tendon-derived type I collagen nerve wrapping. A total of 120 patients with peripheral nerve injury were recruited from Beijing Jishuitan Hospital, The First Bethune Hospital of Jilin University, and Yantai Yuhuangding Hospital, China. The patients were randomly assigned to undergo end-to-end and tension-free neurorrhaphy with nerve matrix membrane(n = 60, 52 male, 8 female, mean age 41.34 years, experimental group) or tendon-derived collagen nerve wrapping(n = 60, 42 male, 18 female, mean age 40.17 years, control group). Patients were followed-up at 14 ± 5, 30 ± 7, 90 ± 10 and 180 ± 20 days after the operation. Safety evaluation included analyses of local and systemic reactions, related laboratory tests, and adverse reactions. Efficacy evaluation included a static 2-point discrimination test, a moving 2-point discrimination test, and a Semmes–Weinstein monofilament examination. Sensory nerve function was evaluated with the British Medical Research Council Scale and Semmes–Weinstein monofilament examination. The ratio(percentage) of patients with excellent to good results in sensory nerve recovery 180 ± 20 days after the treatment was used as the primary effectiveness index. The percentages of patients with excellent to good results in the experimental and control groups were 98.00% and 94.44%, respectively, with no significant difference between the two groups. There were no significant differences in the results of routine blood tests, liver and renal function tests, coagulation function tests, or immunoglobulin tests at 14 and 180 days postoperatively between the two groups. These findings suggest that the novel nerve matrix membrane is similar in efficacy to the commercially-available bovine-derived collagen membrane in the repair of peripheral nerve injury, and it may therefore serve as an alternative in the clinical setting. The clinical trial was approved by the Institutional Ethics Committee of Beijing Jishuitan Hospital, China(approval No. 20160902) on October 8, 2016, the Institutional Ethics Committee of the First Bethune Hospital of Jilin University, China(approval No. 160518-088) on December 14, 2016, and the Institutional Ethics Committee of Yantai Yuhuangding Hospital, China(approval No. 2016-10-01) on December 9, 2016. The clinical trial was registered with the Chinese Clinical Trial Registry(registration number: Chi CTR2000033324) on May 28, 2020.展开更多
Although several surgical procedures exist for treating cubital tunnel syndrome, the best surgical option remains controversial. To evaluate the efficacy of anterior subcutaneous transposition of the ulnar nerve in pa...Although several surgical procedures exist for treating cubital tunnel syndrome, the best surgical option remains controversial. To evaluate the efficacy of anterior subcutaneous transposition of the ulnar nerve in patients with moderate to severe cubital tunnel syndrome and to analyze prognostic factors, we retrospectively reviewed 62 patients(65 elbows) diagnosed with cubital tunnel syndrome who underwent anterior subcutaneous transposition. Preoperatively, the initial severity of the disease was evaluated using the Mc Gowan scale as modified by Goldberg: 18 patients(28%) had grade IIA neuropathy, 20(31%) had grade IIB, and 27(42%) had grade III. Postoperatively, according to the Wilson & Krout criteria, treatment outcomes were excellent in 38 patients(58%), good in 16(25%), fair in 7(11%), and poor in 4(6%), with an excellent and good rate of 83%. A negative correlation was found between the preoperative Mc Gowan grade and the postoperative Wilson & Krout score. The patients having fair and poor treatment outcomes had more advanced age, lower nerve conduction velocity, and lower action potential amplitude compared with those having excellent and good treatment outcomes. These results suggest that anterior subcutaneous transposition of the ulnar nerve is effective and safe for the treatment of moderate to severe cubital tunnel syndrome, and initial severity, advancing age, and electrophysiological parameters can affect treatment outcome.展开更多
The distribution of sensory symptoms in carpal tunnel syndrome is strongly dependent on the degree of electrophysiological dysfunction of the median nerve. The association between carpal tunnel syndrome and ulnar nerv...The distribution of sensory symptoms in carpal tunnel syndrome is strongly dependent on the degree of electrophysiological dysfunction of the median nerve. The association between carpal tunnel syndrome and ulnar nerve entrapment is still unclear. In this study, we measured ulnar nerve function in 82 patients with carpal tunnel syndrome. The patients were divided into group I with minimal carpal tunnel syndrome (n = 35) and group II with mild to moderate carpal tunnel syndrome (n = 47) according to electrophysiological data. Sixty-one age- and sex-matched subjects without carpal tunnel syndrome were used as a control group. There were no significant differences in ulnar sensory nerve peak latencies or conduction velocities from the 4th and 5th fingers between patients with carpal tunnel syndrome and the control group. The ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were lower in patients with carpal tunnel syndrome than in the control group. The ratios of the ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were almost the same in patients with carpal tunnel syndrome as in the control group. These findings indicate that in patients with minimal to moderate carpal tunnel syndrome, there is some electrophysiological evidence of traction on the adjacent ulnar nerve fibers. The findings do not indicate axonal degeneration of the ulnar nerve.展开更多
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 the National Natural Science Foundation of China,No.81971177(to YK)the Natural Science Foundation of Beijing,No.7222198(to NH)the Peking University People's Hospital Research and Development Fund,No.RDX2021-01(to YK)。
文摘FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.
文摘End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve.It involves suturing the distal stump of the disconnected nerve(recipient nerve) to the side of the intimate adjacent nerve(donor nerve).However,the motor-sensory specificity after end-to-side neurorrhaphy remains unclear.This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy.Thirty rats were randomized into three groups:(1) end-to-side neurorrhaphy using the ulnar nerve(mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve;(2) the sham group:ulnar nerve and cutaneous antebrachii medialis nerve were just exposed;and(3) the transected nerve group:cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied.At 5 months,acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group,and none of the myelinated axons were stained in either the sham or transected nerve groups.Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%.In contrast,no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment.These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.
基金supported by the Science and Research Fund of Academic Department in Yunnan Province in China,No.2011C08
文摘Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013:221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.
基金supported by the National Natural Science Foundation of China,No.81371389,31500927,31300942,81201017the Collegiate Natural Science Foundation of Jiangsu Province of China,No.13KJB180018the Natural Science Foundation of Nantong University of China,No.14ZY013
文摘The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A m RNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration.
基金supported by Canadian Institutes of Health Research(CIHR)grants#74747 and#14238(both to VMKV)Natural Sciences and Science and Engineering Research Council(NSERC)of Canada grant(to VM)supported by University of Saskatchewan College of Graduate and Postdoctoral Studies Scholarships。
文摘Emerging evidence supports that the stress response to peripheral nerve injury extends beyond the injured neuron,with alterations in associated transcription factors detected both locally and remote to the lesion.Stress-induced nuclear translocation of the transcription factor forkhead class box O3a(FOXO3a)was initially linked to activation of apoptotic genes in many neuronal subtypes.However,a more complex role of FOXO3a has been suggested in the injury response of sensory neurons,with the injured neuron expressing less FOXO3a.To elucidate this response and test whether non-injured sensory neurons also alter FOXO3a expression,the temporal impact of chronic unilateral L4–6 spinal nerve transection on FOXO3a expression and nuclear localization in adult rat dorsal root ganglion neurons ipsilateral,contralateral or remote to injury relative to na?ve controls was examined.In na?ve neurons,high cytoplasmic and nuclear levels of FOXO3a colocalized with calcitonin gene related peptide,a marker of the nociceptive subpopulation.One hour post-injury,an acute increase in nuclear FOXO3a in small size injured neurons occurred followed by a significant decrease after 1,2 and 4 days,with levels increasing toward pre-injury levels by 1 week post-injury.A more robust biphasic response to the injury was observed in uninjured neurons contralateral to and those remote to injury.Nuclear levels of FOXO3a peaked at 1 day,decreased by 4 days,then increased by 1 week post-injury,a response mirrored in C4 dorsal root ganglion neurons remote to injury.This altered expression contralateral and remote to injury supports that spinal nerve damage has broader systemic impacts,a response we recently reported for another stress transcription factor,Luman/CREB3.The early decreased expression and nuclear localization of FOXO3a in the injured neuron implicate these changes in the cell body response to injury that may be protective.Finally,the broader systemic changes support the existence of stress/injury-induced humeral factor(s)influencing transcriptional and potentially behavioral changes in uninjured dorsal root ganglion neurons.Approval to conduct this study was obtained from the University of Saskatchewan Animal Research Ethics Board(protocol#19920164).
基金Medical Scholarship Foundation of Sasakawa Fellowship of Japan
文摘BACKGROUND: In recent years, surgeons have advocated root or trunk repair of avulsed nerve roots for overall recovery. However, donor nerves pose a major problem, because they do not contain adequate numbers of axons. Moreover, the procedures lead to nerve deficits in the donor nerve following transplantation. OBJECTIVE: To observe whether axonal regeneration occurs by end-to-side neurorrhaphy in the peripheral nerve and spinal cord. DESIGN, TIME AND SETTING: A neuroanatomical, randomized, controlled, animal study was performed at Functional Anatomy Lab in Nagoya University School of Medicine from May 2002 to July 2003. MATERIALS: Fluorogold was purchased from Fluorochrome, LLC, USA. BX50 light microscope and fluorescent microscope were purchased from Olympus, Japan. METHODS: A total of 21 rats were randomly divided into three groups, and the posterior avulsion injury model (C6-8) of the brachial plexus was performed. In the ventral root graft group, the avulsed C7 ventral roots were reanastomosed to the small anterior lateral aspect window of the spinal cord via nerve grafts. In the dorsal root graft group, the C7 dorsal roots were reanastomosed at the small pia mater window of the posterior lateral aspect of the spinal cord via nerve grafts. In the control group, the avulsed nerve roots were not repaired. MAIN OUTCOME MEASURES: The nerve grafts were collected from the ventral and dorsal root graft groups, and the C7 proximal nerve end was collected from the control group. Acetylcholinesterase staining was performed on the tissue. Fluorogold retrograde tracing technique was applied to determine the origin of the regenerating axons. RESULTS: Results showed that acetylcholine-positive axons existed in nerve grafts of the ventral and dorsal root graft groups. However, axons were not found in the avulsed nerve roots of the control group. Fluorogold retrograde tracing confirmed the presence of fluorogold-containing neurons in the ventral and dorsal horn of the ventral and dorsal root graft groups. Fluorogold-positive neurons were not observed in the control group. CONCLUSION: End-to-side neurorrhaphy induced axonal regeneration from the spinal cord to the peripheral nervous system.
基金supported by grants from the Natural Science Foundation of Tianjin(General Program),Nos.23JCYBJC01390(to RL),22JCYBJC00220(to XC),and 22JCYBJC00210(to QL).
文摘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.
基金the Science and Technology Foundation of Shenyang in China,No.F10-217-1-00
文摘In this study, we loaded human umbilical cord mesenchymal stem cells onto human amniotic membrane with epithelial cells to prepare nerve conduits, i.e., a relatively closed nerve regeneration chamber. After neurolysis, the injured radial nerve was enwrapped with the prepared nerve conduit, which was fixed to the epineurium by sutures, with the cell on the inner surface of the conduit. Simultaneously, a 1.0 mL aliquot of human umbilical cord mesenchymal stem cell suspension was injected into the distal and proximal ends of the injured radial nerve with 1.0 cm intervals. A total of 1.75 x 107 cells were seeded on the amniotic membrane. In the control group, patients received only neurolysis. At 12 weeks after cell transplantation, more than 80% of patients exhibited obvious improvements in muscular strength, and touch and pain sensations. In contrast, these improvements were observed only in 55-65% of control patients. At 8 and 12 weeks, muscular electrophysiological function in the region dominated by the injured radial nerve was significantly better in the transplantation group than the control group. After cell transplantation, no immunological rejections were observed. These findings suggest that human umbilical cord mesenchymal stem cell-loaded amniotic membrane can be used for the repair of radial nerve injury.
基金supported by a grant of the Korea Healthcare Technology R&D Project,Ministry for Health,Welfare & Family Affairs,Republic of Korea,No.A101578
文摘Human periodontal ligament stem cells are easily accessible and can differentiate into Schwann cells. We hypothesized that human periodontal ligament stem cells can be used as an alternative source for the autologous Schwann cells in promoting the regeneration of injured peripheral nerve. To validate this hypothesis, human periodontal ligament stem cells (1 × 106) were injected into the crush-injured left mental nerve in rats. Simultaneously, autologous Schwann cells (1 × 106) and PBS were also injected as controls. Real-time reverse transcriptase polymerase chain reaction showed that at 5 days after injection, mRNA expression of low affinity nerve growth factor receptor was sig-nificantaly increased in the left trigeminal ganglion of rats with mental nerve injury. Sensory tests, histomorphometric evaluation and retrograde labeling demonstrated that at 2 and 4 weeks after in-jection, sensory function was significantly improved, the numbers of retrograde labeled sensory neurons and myelinated axons were significantly increased, and human periodontal ligament stem cells and autologous Schwann cells exhibited similar therapeutic effects. These findings suggest that transplantation of human periodontal ligament stem cells show a potential value in repair of mental nerve injury.
基金supported by the Wu Jieping Medical Foundation of China,No. 320.6750.17273 (to YBG)。
文摘A new nerve matrix membrane derived from decellularized porcine nerves has been shown to retain the major extracellular matrix components, and to be effective in preventing adhesion between the nerve anastomosis sites and the surrounding tissues in a rat sciatic nerve transection model, thereby enhancing regeneration of the nerve. The effectiveness of the membrane may be attributed to its various bioactive components. In this prospective, randomized, single-blind, parallel-controlled multicenter clinical trial, we compared the safety and efficacy of the new nerve matrix membrane with a previously approved bovine tendon-derived type I collagen nerve wrapping. A total of 120 patients with peripheral nerve injury were recruited from Beijing Jishuitan Hospital, The First Bethune Hospital of Jilin University, and Yantai Yuhuangding Hospital, China. The patients were randomly assigned to undergo end-to-end and tension-free neurorrhaphy with nerve matrix membrane(n = 60, 52 male, 8 female, mean age 41.34 years, experimental group) or tendon-derived collagen nerve wrapping(n = 60, 42 male, 18 female, mean age 40.17 years, control group). Patients were followed-up at 14 ± 5, 30 ± 7, 90 ± 10 and 180 ± 20 days after the operation. Safety evaluation included analyses of local and systemic reactions, related laboratory tests, and adverse reactions. Efficacy evaluation included a static 2-point discrimination test, a moving 2-point discrimination test, and a Semmes–Weinstein monofilament examination. Sensory nerve function was evaluated with the British Medical Research Council Scale and Semmes–Weinstein monofilament examination. The ratio(percentage) of patients with excellent to good results in sensory nerve recovery 180 ± 20 days after the treatment was used as the primary effectiveness index. The percentages of patients with excellent to good results in the experimental and control groups were 98.00% and 94.44%, respectively, with no significant difference between the two groups. There were no significant differences in the results of routine blood tests, liver and renal function tests, coagulation function tests, or immunoglobulin tests at 14 and 180 days postoperatively between the two groups. These findings suggest that the novel nerve matrix membrane is similar in efficacy to the commercially-available bovine-derived collagen membrane in the repair of peripheral nerve injury, and it may therefore serve as an alternative in the clinical setting. The clinical trial was approved by the Institutional Ethics Committee of Beijing Jishuitan Hospital, China(approval No. 20160902) on October 8, 2016, the Institutional Ethics Committee of the First Bethune Hospital of Jilin University, China(approval No. 160518-088) on December 14, 2016, and the Institutional Ethics Committee of Yantai Yuhuangding Hospital, China(approval No. 2016-10-01) on December 9, 2016. The clinical trial was registered with the Chinese Clinical Trial Registry(registration number: Chi CTR2000033324) on May 28, 2020.
基金supported by grants from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542200a grant from Innovation Program of Ministry of Education,No.IRT1201+1 种基金the National Natural Science Foundation of China,No.31271284,31171150,81171146,30971526,31100860,31040043,31371210Program for New Century Excellent Talents in University of Ministry of Education of China,No.BMU20110270
文摘Although several surgical procedures exist for treating cubital tunnel syndrome, the best surgical option remains controversial. To evaluate the efficacy of anterior subcutaneous transposition of the ulnar nerve in patients with moderate to severe cubital tunnel syndrome and to analyze prognostic factors, we retrospectively reviewed 62 patients(65 elbows) diagnosed with cubital tunnel syndrome who underwent anterior subcutaneous transposition. Preoperatively, the initial severity of the disease was evaluated using the Mc Gowan scale as modified by Goldberg: 18 patients(28%) had grade IIA neuropathy, 20(31%) had grade IIB, and 27(42%) had grade III. Postoperatively, according to the Wilson & Krout criteria, treatment outcomes were excellent in 38 patients(58%), good in 16(25%), fair in 7(11%), and poor in 4(6%), with an excellent and good rate of 83%. A negative correlation was found between the preoperative Mc Gowan grade and the postoperative Wilson & Krout score. The patients having fair and poor treatment outcomes had more advanced age, lower nerve conduction velocity, and lower action potential amplitude compared with those having excellent and good treatment outcomes. These results suggest that anterior subcutaneous transposition of the ulnar nerve is effective and safe for the treatment of moderate to severe cubital tunnel syndrome, and initial severity, advancing age, and electrophysiological parameters can affect treatment outcome.
文摘The distribution of sensory symptoms in carpal tunnel syndrome is strongly dependent on the degree of electrophysiological dysfunction of the median nerve. The association between carpal tunnel syndrome and ulnar nerve entrapment is still unclear. In this study, we measured ulnar nerve function in 82 patients with carpal tunnel syndrome. The patients were divided into group I with minimal carpal tunnel syndrome (n = 35) and group II with mild to moderate carpal tunnel syndrome (n = 47) according to electrophysiological data. Sixty-one age- and sex-matched subjects without carpal tunnel syndrome were used as a control group. There were no significant differences in ulnar sensory nerve peak latencies or conduction velocities from the 4th and 5th fingers between patients with carpal tunnel syndrome and the control group. The ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were lower in patients with carpal tunnel syndrome than in the control group. The ratios of the ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were almost the same in patients with carpal tunnel syndrome as in the control group. These findings indicate that in patients with minimal to moderate carpal tunnel syndrome, there is some electrophysiological evidence of traction on the adjacent ulnar nerve fibers. The findings do not indicate axonal degeneration of the ulnar nerve.