Functional recovery of the hand following brachial plexus injury (BPI) is highly dependent on preventing atrophy of the intrinsic muscles of the hand. Although electrical muscle stimulation (EMS) is an effective therapeutic approach for atrophy, its underlying mechanisms remain poorly elucidated. This study investigated the biological mechanisms through which EMS-induced muscle contraction inhibits the progression of denervation-induced atrophy. Using a rat model of total BPI, we validated the protective effect of EMS against atrophy in denervated intrinsic muscles. Whole-cell patch-clamp analysis confirmed the functional role of the L-type voltage-gated calcium channel in this process. We further discovered that EMS rectifies the aberrant elevation of intracellular Ca2+ concentration resulting from Cav1.1 dysfuntion. In vitro cellular experiments revealed that a rise in cytosolic Ca2+ activates the translation rather than transcription of IGF-1. Crucially, long-term and regular EMS sustains elevated IGF-1 levels, which subsequently modulates protein metabolism in myocytes, thereby mitigating denervated muscle atrophy.

Cerebral palsy (CP) is a neurodevelopmental disorder characterized by spasticity, which significantly impairs motor function. Traditional treatments offer limited relief and carry risks. Repetitive peripheral magnetic stimulation (rPMS) presents a promising non-invasive alternative. This study aimed to evaluate the efficacy of rPMS in managing triceps surae spasticity in children with CP and to identify factors influencing its effectiveness. A retrospective cohort study was conducted with 271 children aged 6–12 years with CP (GMFCS levels I-II). Participants were assigned to conventional treatment (n = 131) or rPMS (n = 140) groups. Outcomes were assessed using the Modified Tardieu Scale (MTS), Berg balance scale (BSS), Edinburgh Visual Gait Score (EVGS) and integrated electromyography (IEMG). Treatment efficacy was defined based on improvements in the Gross Motor Function Measure-88 (GMFM-88). Logistic regression identified factors influencing rPMS efficacy. The rPMS group showed significantly greater improvements in spasticity (reduced MTS and EVGS scores), balance (increased BBS scores), and muscle coordination (IEMG changes) compared to the conventional group (P < 0.05). The overall effectiveness rate was 85.00

PURPOSE:The purpose of this study is to present our long-term follow-up outcomes on the use of the contralateral C7 (CC7) transfer to reinnervate three recipient nerves in patients with total brachial plexus avulsion (BPA). METHODS:We retrospectively reviewed data from 13 patients with total BPA. All patients were diagnosed with phrenic and accessory nerve injury on the affected side. Five patients were 20 years or younger, and eight patients were older than 20 years at the time of surgery. In the first stage, the entire CC7 was harvested and transferred to the pedicled ulnar nerve and the suprascapular nerve with a sural nerve graft. The ulnar nerve was transferred to the median nerve and biceps branch in the second stage about 4 to 8 months after the first stage. The British Medical Research Council (MRC) grading system was used for motor and sensory assessment. RESULTS:Of the 13 cases, 11 obtained equal or more M3 of shoulder abduction strength, and the effective rate of recovery was 84.62%. The effective rates were 53.85% (7/13) for shoulder external rotation, 84.62% (11/13) for elbow flexion, 61.54% (8/13) for wrist and finger flexion, and 53.85% (7/13) in median nerve area sensation. The recovery of median nerve function in the younger age group was significantly better than in the older group (p < 0.05). CONCLUSIONS:The use of CC7 transfer for simultaneous repair of the suprascapular nerve, median nerve, and biceps branch may become an option for the treatment of total BPA combined with phrenic nerve and spinal accessory nerve injuries.

Spinal microglia and astrocytes are both involved in neuropathic and inflammatory pain, which may display sexual dimorphism. Here, we demonstrate that the sustained activation of spinal astrocytes and astrocyte-derived interleukin (IL)-17A promotes the progression of mouse bone cancer pain without sex differences. Chemogenetic or pharmacological inhibition of spinal astrocytes effectively ameliorates bone cancer-induced pain-like behaviors. In contrast, chemogenetic or optogenetic activation of spinal astrocytes triggers pain hypersensitivity, implying that bone cancer-induced astrocytic activation is involved in the development of bone cancer pain. IL-17A expression predominantly in spinal astrocytes, whereas its receptor IL-17 receptor A (IL-17RA) was mainly detected in neurons expressing VGLUT2 and PAX2, and a few in astrocytes expressing GFAP. Specific knockdown of IL-17A in spinal astrocytes blocked and delayed the development of bone cancer pain. IL-17A overexpression in spinal astrocytes directly induced thermal hyperalgesia and mechanical allodynia, which could be rescued by CaMKIIα inhibitor. Moreover, selective knockdown IL-17RA in spinal Vglut2 + or Vgat +neurons, but not in astrocytes, significantly blocked the bone cancer-induced hyperalgesia. Together, our findings provide evidence for the crucial role of sex-independent astrocytic signaling in bone cancer pain. Targeting spinal astrocytes and IL-17A/IL-17RA-CaMKIIα signaling may offer new gender-inclusive therapeutic strategies for managing bone cancer pain.

Background Contralateral C7 transfer (cC7) is an important treatment for total brachial plexus avulsion (TBPA), which sacrifices the recovery of the ulnar nerve (UN). The present study aimed to introduce an animal model of modified cC7 that preserved the deep branch of ulnar nerve (dbUN) and verify its feasibility. Methods Anatomical study: Lengths, diameters, and axon counts of dbUN and anterior interosseous (AIN) branches in six rats were measured. In vivo surgery: 18 rats were divided into three groups. Group A: Traditional cC7. Group B: Modified cC7 finished in one stage. Group C: Modified cC7 and AIN branch anastomosed with dbUN one month after the first stage. Electrophysiological examinations, muscle wet weight, muscle cross-sectional areas, and nerve axon counts were evaluated six months postoperatively. Results Anatomical study: The distances from dbUN and AIN branches to the midpoint of the inner and outer epicondyles connection of the humerus, diameters, and axon numbers of dbUN and AIN branches were analyzed, then AIN terminal branch (tbAIN) was anastomosed with dbUN. In vivo surgery: The differences in median nerve fiber counts were not significant. There were more UN axons in group A than in groups B and C. In electrophysiological examinations, muscle wet weight and cross-sectional area of the flexor digitorum profundus showed no significant difference, but the second interosseus cross-sectional areas in groups B and C were significantly larger than in group A. Conclusions This study established an animal model of preserving dbUN in cC7 and verified its feasibility. The possibility of restoring dbUN was established.

Contralateral C7 (cC7) transfer is a technique used in patients with total brachial plexus avulsion. An ulnar nerve graft (UNG) is usually used, as intrinsic function is not expected to be restored due to length of reinnervation required. In this study, we attempted to improve intrinsic function recovery by preserving the deep branch of the ulnar nerve (dbUN) and reanimating it with the anterior interosseous nerve (AIN) after cC7 transfer. Fifty-four rats were divided into the following three groups: Group A, traditional cC7 transfer to the median nerve with a UNG; Group B, cC7 transfer preserving and repairing the dbUN with the terminal branch of the AIN; Group C, same as Group B; however, the dbUN was coapted after 1 month with the AIN. At 3, 6 and 9 months postoperatively, the results of electrodiagnostic and histomorphometric examinations of the interosseous muscle were significantly better in Groups B and C, without affecting AIN recovery. In conclusion, the modified cC7 transfer technique can potentially improve intrinsic function recovery without affecting median nerve recovery.

The contralateral seventh cervical (cC7) nerve root transfer represents a cornerstone technique in treating total brachial plexus avulsion injury. Traditional cC7 procedures employ the entire ulnar nerve as a graft, which inevitably compromises its restorative capacity.Our cadaveric study seeks to assess this innovative approach aimed at preserving the motor branch of the ulnar nerve (MBUN). This new method aims to enable future repair stages, using the superficial radial nerve (SRN) as a bridge connecting cC7 and MBUN.We undertook a comprehensive dissection of ten adult cadavers, generously provided by the Department of Anatomy, Histology, and Embryology at Fudan University, China. It allowed us to evaluate the feasibility of our proposed technique. For this study, we harvested only the dorsal and superficial branches of the ulnar nerve, as well as the SRN, to establish connections between the cC7 nerve and recipient nerves (both the median nerve and MBUN). We meticulously dissected the SRN and the motor and sensory branches of the ulnar nerve. Measurements were made from the reverse point of the SRN to the wrist flexion crease and the coaptation point of the SRN and MBUN. Additionally, we traced the MBUN from distal to proximal ends, recording its maximum length. We also measured the diameters of the nerve branches and tallied the number of axons.Our modified approach proved technically viable in all examined limbs. The distances from the reverse point of the SRN to the wrist flexion crease were 8.24 ± 1.80 cm and to the coaptation point were 6.60 ± 1.75 cm. The maximum length of the MBUN was 7.62 ± 1.03 cm. The average axon diameters in the MBUN and the anterior and posterior branches of the SRN were 1.88 ± 0.42 mm、1.56 ± 0.38 mm、2.02 ± 0.41 mm,respectively. The corresponding mean numbers of axons were 1426.60 ± 331.39 and 721.50 ± 138.22, and 741.90 ± 171.34, respectively.The SRN demonstrated the potential to be transferred to the MBUN without necessitating a nerve graft. A potential advantage of this modification is preserving the MBUN's recovery potential.

Previous studies suggested that the mode of donor transection is a critical factor affecting the efficacy of the contralateral C7 (CC7) nerve transfer. Nevertheless, the mechanism underlying this phenomenon remains elusive. The aim of this study was to investigate the relationship between the division modes of the CC7 nerve and cortical functional reorganization of Sprague-Dawley rats. We hypothesized that different methods of CC7 nerve transection might induce differences in cortical functional reorganization, thus resulting in differences in surgery efficacy. BDNF, TNF-α/IL-6, and miR-132/134 were selected as indicators of cortical functional reorganization. No significant differences in all these indicators were noted between the entire group and the entire root+posterior division group (P > 0.05). BDNF and miR-132/134 levels in the entire group and the entire root+posterior division group were significantly increased compared with their levels in the posterior group and the blank control group (P < 0.001). In all groups, BDNF, TNF-α/IL-6, and miR-132/134 levels in both hemispheres initially increased and subsequently decreased until week 40. In conclusion, this study provided the evidence of dynamic changes in BDNF, TNF-α/IL-6, and miR-132/134 in the cortex of rats after CC7 nerve transfer using different transecting modes, demonstrating that different CC7 nerve divisions might result in different surgical effects through modulation of cortical reorganization.

After brachial plexus avulsion (BPA),microglia induce inflammation,initiating and maintaining neuropathic pain.EZH2 (enhancer of zeste homolog 2) has been implicated in inflammation and neuropathic pain,but the mechanisms by which it regulates neuropathic pain remain unclear.Here,we found that EZH2 levels were markedly upregulated during BPA-induced neuropathic pain in vivo and in vitro,stimulating pro-inflammatory cytokines (IL-1 β,TNF-α,and IL-6) secretion in vivo.In rats with BPA-induced neuropathic pain,mechanical and cold hypersensitivities were induced by EZH2 upregulation and inhibited by EZH2 downregulation in the anterior cingulate cortex.Microglial autophagy was also significantly inhibited,with EZH2 inhibition activating autophagy and reducing neuroinflammation in vivo.However,this effect was impaired by inhibiting autophagy with 3-methyladenine,suggesting that the MTOR signaling pathway is a functional target of EZH2.These data suggest that EZH2 regulates neuroinflammation and neuropathic pain via a novel MTOR-mediated autophagy signaling pathway,providing a promising approach for managing neuropathic pain.

Recently programmed death-ligand 1 (PD-L1) receptor PD-1 was found in dorsal root ganglion (DRG) neurons, and PD-L1 activates PD-1 to inhibit inflammatory and neuropathic pain by modulating neuronal excitability. However, the downstream signaling of PD-1 in sensory neurons remains unclear. Here, we show that PD-L1 activated Src homology 2 domain-containing tyrosine phosphatase-1 (SHP-1) to downregulate transient receptor potential vanilloid 1 (TRPV1) in DRG neurons and inhibit bone cancer pain in mice. Local injection of PD-L1 produced analgesia. PD-1 in DRG neurons colocalized with TRPV1 and SHP-1. PD-L1 induced the phosphorylation of SHP-1 in DRG TRPV1 neurons and inhibited TRPV1 currents. Loss of TRPV1 in mice abolished bone cancer–induced thermal hyperalgesia and PD-L1 analgesia. Conditioned deletion of SHP-1 in NaV1.8+ neurons aggravated bone cancer pain and diminished the inhibition of PD-L1 on TRPV1 currents and pain. Together, our findings suggest that PD-L1/PD-1 signaling suppresses bone cancer pain via inhibition of TRPV1 activity. Our results also suggest that SHP-1 in sensory neurons is an endogenous pain inhibitor and delays the development of bone cancer pain via suppressing TRPV1 function.

Objectives: The goal of this study was to compare clinical characteristics of neuropathic pain associated with total brachial plexus injury before and after surgeries and to correlate possible contributing factors concerning to the pain prognosis. Patients and methods: Thirty patients with both total brachial plexus injury and neuropathic pain were included. Neuropathic pain was evaluated in terms of pain intensities, symptoms and regions. Pain intensities were evaluated by a visual analogue scale. The Neuropathic Pain Symptoms Inventory questionnaire and body maps were used to compare the pain symptoms and regions. Demographic data, injury and repair information were evaluated to analyze the possible factors influencing the prognosis. Results: The average pain score of all participants was 7.13 +/- 2.46 preoperatively and 5.40 +/- 2.08 postoperatively. All patients were divided into Pain Relief Group and Pain Aggravation Group. Older age (p=0.042), machine traction injury (p=0.019)and nerve transplantation(p=0.015) seemed to be related with pain aggravation. Paroxysmal pain was aggravated after surgical repairs (p=0.041), while paresthesia/dysesthesia improved after surgery (p=0.003). The permanent component of the pain (spontaneous pain) did not show any significant change (p=0.584). Pain in C5 (p < 0.001) and C6 (p=0.031) dermatomes got relieved after surgery. Conclusion: This study revealed the neuropathic pain of most patients with total brachial plexus injury was alleviated after neurosurgery, and the pain prognosis of different symptoms and regions varied after the nerve repair.

Objective To verify the safety of a new surgical model by assessing the lung function of phrenic nerve and intercostal nerve via side-to-side with nerve autograff to the neurorrhaphy site of the musculocutaneous nerve in rats.Methods Fifty four SD rats were randomly divided into three groups.Group A was the negative control group,in which the musculocutaneous nerve was transected and directly sutured.The other two groups were the phrenic nerve (group B) and intercostal nerve (group C):after the musculocutaneous nerve was transected and the side-to-side neurorrhaphy was conducted.Sural nerve was used to connect the musculocutaneous nerve neurorrhaphy site and the donor nerve as phrenic nerve or intercostal nerve.Lung function test was conducted at 1,2 and 3 months postoperatively.Results No significant difference was detected from each parameter including breathing frequency (F),minute ventilation (MV),inspirationand expiration time (Ti and Te),peak inspiratory and expiratory flow (PIF and PEF) and 50％ expiratory flow (EF50) of lung function test among group A,B and C at 1,2 and 3 months postoperatively.Conclusion Side-to-side neurorrhaphy has no obvious damage to pulmonary function.This new method is safe and has great advantages in clinical application.

Purpose: Neuropathic pain (NP) is a challenging clinical problem due to its complex pathogenesis. In our previous study using microarray, we found that the levels of lncRNA Malat1 were decreased in the spinal cord of NP rat after brachial plexus avulsion, but its contribution to NP remain unclear. The purpose of this study was to investigate its role in the pathogenesis of NP. Methods: In the NP model of complete brachial plexus avulsion rat, spinal cords were harvested, and fluorescence in situ hybridization (FISH) was used to test the spatial expression of Malat1 and qRT-PCR was used to confirm the quantitative expression of Malat1. In primary cultured neurons, Malat1 expression interfered with adenovirus. Spontaneous electric activities of neurons were tested using multi-electrode arrays and apoptosis of neurons was tested using TUNEL method. The change of intracellular calcium concentration was analyzed using calcium imaging method. Results: Decreased Malat1 expression was confirmed using qRT-PCR, and Malat1 was identified in the cytoplasm of neurons in spinal cord, but not in glia. In vitro, the decrease of Malat1 resulted in an increase in the frequency of spontaneous electric activity in neurons but had no effect on neuronal apoptosis. Further analysis indicated during glutamate stimulation, the change of intracellular calcium concentration in neurons with downregulated Malat1 expression was significantly greater than that in normal neurons. Conclusion: Reduced Malat1 expression may induce NP by increasing neuronal excitability in the spinal cord via regulation of calcium flux.

The purpose of this study was to compare the effects of single and dual nerve transfer for the repair of shoulder abduction in patients with upper or upper and middle trunk root avulsion. We carried out a retrospective analysis of 20 patients with C5-C6 or C5-C7 root avulsion treated by nerve transfer in our hospital. The patients were divided into two groups according to the different operation methods. In group A, ten patients had transferred the spinal accessory nerve to the suprascapular nerve. Ten patients in group B underwent dual nerve transfer to reconstruct shoulder abduction, including the spinal accessory nerve transfer to the suprascapular nerve and two intercostal nerves or the long head of triceps nerve branch transfer to the anterior branch of the axillary nerve. There was no difference in age, preoperative interval, follow-up time, and injury type between the two groups. We used shoulder abduction strength, shoulder abduction angle, and Samardzic’s shoulder joint evaluation standard as the postoperative evaluation index. Shoulder abductor muscle strength equals or above M3 was considered to be an effective recovery. Of the 20 cases, 15 obtained equals or more M3 of shoulder abduction strength, and the overall effective rate was 75%. The effective rate of shoulder abduction power in group A was 60% (6/10) while group B was 90% (9/10); however, the difference was not statistically significant (p > 0.05). The average shoulder abduction angle was 55° (SD = 19.29) in group A and 77° (SD = 20.44) in group B; the angle was significantly better in group B than that in group A (p < 0.05). Based on Samardzic’s standard, the excellent and good rate of group A was 90% and in group B was 50%. The difference was statistically significant (p < 0.05). For patients with nerve root avulsion of C5-C6 or C5-C7, repairing suprascapular nerve and axillary nerve at the same time is more effective than repairing suprascapular nerve alone in terms of shoulder abduction angle and excellent rate of functional recovery of the shoulder joint. Therefore, we recommend the repair of the suprascapular nerve and the axillary nerve simultaneously if conditions permit.

Objective To investigate the role of miR-124 and miR-138 in regulating the brain trans-hemispheric functional reorganization after the contralateral C7 transfer. Methods According to the model establishment and surgical treatment, 126 male SD rats were divided randomly into three groups: operation group, simple avulsion group and sham group. In the operation group, the right total brachial plexus avulsion model was made and the left C7 nerve root was cut as a donor to repair the right median nerve through ulnar nerve bridging. In the simple avulsion group, only the right total brachial plexus avulsion model was made and the left brachial plexus was only exposed. The sham group only exposed the bilateral brachial plexus. RT-PCR was used to detect the expression of miR-124 and miR-138 in bilateral brain motor cortex of rats at different time points after operation, and the correlation was analyzed. Results The expression level of miR-124 and miR-138 in the operation group and simple avulsion group showed dynamic changes with time, while in the sham group they showed no significant difference between different time points. The expression level of miR-124 and miR-138 in the operation group were greater than those in the simple avulsion group, and those in the simple avulsion group was higher than those in the sham operation group (P<0.05). There was no significant difference in the expression of miR-124 and miR-138 of the operation group and the sham operation at each point after operation between brain left and right hemispheres (P>0.05). The expression levels of miR-124 and miR-138 in the left hemisphere of the simple avulsion group were significantly higher than those in the right hemisphere (P<0.05). Conclusion The miR-124 and miR-138 may be invovled in the regulation of brain function remodeling after the contralateral C7 nerve transfer.

Contralateral C7 nerve transfer surgery is one of the most important surgical techniques for treating total brachial plexus nerve injury. In the traditional contralateral C7 nerve transfer surgery, the whole ulnar nerve on the paralyzed side is harvested for transfer, which completely sacrifices its potential of recovery. In the present, novel study, we report on the anatomical feasibility of a modified contralateral C7 nerve transfer surgery. Ten fresh cadavers (4 males and 6 females) provided by the Department of Anatomy, Histology, and Embryology at the Medical College of Fudan University, China were used in modified contralateral C7 nerve transfer surgery. In this surgical model, only the dorsal and superficial branches of the ulnar nerve and the medial antebrachial cutaneous nerve on the paralyzed side (left) were harvested for grafting the contralateral (right) C7 nerve and the recipient nerves. Both the median nerve and deep branch of the ulnar nerve on the paralyzed (left) side were recipient nerves. To verify the feasibility of this surgery, the distances between each pair of coaptating nerve ends were measured by a vernier caliper. The results validated that starting point of the deep branch of ulnar nerve and the starting point of the medial antebrachial cutaneous nerve at the elbow were close to each other and could be readily anastomosed. We investigated whether the fiber number of donor and recipient nerves matched one another. The axons were counted in sections of nerve segments distal and proximal to the coaptation sites after silver impregnation. Averaged axon number of the ulnar nerve at the upper arm level was approximately equal to the sum of the median nerve and proximal end of medial antebrachial cutaneous nerve (left: 0.94:1; right: 0.93:1). In conclusion, the contralateral C7 nerve could be transferred to the median nerve but also to the deep branch of the ulnar nerve via grafts of the ulnar nerve without deep branch and the medial antebrachial cutaneous nerve. The advantage over traditional surgery was that the recovery potential of the deep branch of ulnar nerve was preserved. The study was approved by the Ethics Committee of Fudan University (approval number: 2015-064) in July, 2015.

Objective To analyze the relationship between age,course of disease,motor nerve conduction velocity of elbow ulnar nerve and prognosis of severe cubital tunnel syndrome after ulnar nerve anterior transposition.Methods Ninety patients with severe cubital tunnel syndrome treated surgically in our hospital from June 2014 to June 2017 were retrospectively analyzed.The course of disease,age,motor nerve conduction velocity of ulnar nerve in elbow segment before and during operation were recorded,and the improvement rate of nerve conduction velocity was calculated.The correlation between each factor and prognosis was analyzed.Results The follow-up time ranged from 12 to 38 months with an average of 22.2 months.According to Gu Yudong's cubital tunnel syndrome functional evaluation criteria,the results were rated as excellent in 32 cases,good in 49 cases,fair in 8 cases and poor in 1 case.The overall excellent and good rate was 90％.The course of disease,age,preoperative and intraoperative motor nerve conduction velocity of ulnar nerve in elbow segment were correlated with curative effect,but the improvement rate of nerve conduction velocity was not correlated with prognosis.Conclusion Preoperative course and age were negatively correlated with prognosis.Preoperative or post-operative motor nerve conduction velocity was positively correlated with prognosis.However,the improvement rate of motor nerve conduction velocity was not correlated with postoperative efficacy and could not be used as a predictor of clinical prognosis.

Exogenous electrical nerve stimulation has been reported to promote nerve regeneration. Our previous study has suggested that endogenous automatic nerve discharge of the phrenic nerve and intercostal nerve has a positive effect on nerve regeneration at 1 month postoperatively, but a negative effect at 2 months postoperatively, which may be caused by scar compression. In this study, we designed four different rat models to avoid the negative effect from scar compression. The control group received musculocutaneous nerve cut and repair. The other three groups were subjected to side-to-side transfer of either the phrenic (phrenic nerve group), intercostal (intercostal nerve group) or thoracodorsal nerves (thoracic dorsal nerve group), with sural nerve autograft distal to the anastomosis site. Musculocutaneous nerve regeneration was assessed by electrophysiology of the musculocutaneous nerve, muscle tension, muscle wet weight, maximum cross-sectional area of biceps, and myelinated fiber numbers of the proximal and distal ends of the anastomosis site of the musculocutaneous nerve and the middle of the nerve graft. At 1 month postoperatively, compound muscle action potential amplitude of the biceps in the phrenic nerve group and the intercostal nerve group was statistically higher than that in the control group. The myelinated nerve fiber numbers in the distal end of the musculocutaneous nerve and nerve graft anastomosis in the phrenic nerve and the intercostal nerve groups were statistically higher than those in the control and thoracic dorsal nerve groups. The neural degeneration rate in the middle of the nerve graft in the thoracic dorsal nerve group was statistically higher than that in the phrenic nerve and the intercostal nerve groups. At 2 and 3 months postoperatively, no significant difference was detected between the groups in all the assessments. These findings confirm that the phrenic nerve and intercostal nerve have a positive effect on nerve regeneration at the early stage of recovery. This study established an optimized animal model in which suturing the nerve graft to the distal site of the musculocutaneous nerve anastomosis prevented the inhibition of recovery from scar compression.