Brachial Plexus Root Avulsion Research Articles

Brachial Plexus Root Avulsion Injury-Induced Endothelin-Converting Enzyme-Like 1 Overexpression Is Associated with Injured Motor Neurons Survival.

Brachial plexus root avulsion (BPRA) injury arises from challenging delivery during childbirth, sports-related incidents, or car accidents, leading to extensive loss of motor neurons (MNs) and subsequent paralysis, including both motor and sensory impairment. Surgical nerve re-implantation cannot effectively restore motor function, and the survival of injured MNs is vital for axon regeneration and re-innervating the target muscles. Therefore, identifying novel molecular targets to improve injured MNs survival is of great significance in the treatment of BPRA injuries. Endothelin-converting enzyme-like 1 (ECEL1), a membrane-bound metallopeptidase, was initially identified as a molecule associated with nerve injuries. Damaged neurons exhibit a significant increase in the expression of ECEL1 following various types of nerve injuries, such as optic nerve injury and sciatic nerve injury. This study aimed to investigate the relationship between ECEL1 overexpression and the survival of injured MNs following BPRA injury. Our results observed a significant elevation in ECEL1 expression in injured MNs and positively correlated with MNs survival following BPRA injury. The transcription of ECEL1 is regulated by the transcription factors c-Jun and ATF3 in the context of BPRA injury, which is consistent with previous other nerve injuries study. In addition, the expression of TrkA gradually decreases in ECEL1-positive MNs and ECEL1 possibly preserves the activity of downstream AKT-GSK3β pathway of TrkA in injured MNs. In conclusion, our results introduce a promising therapeutic molecular target to assist re-implantation surgery for the treatment of BPRA injury.

Acetylglutamine facilitates motor recovery and alleviates neuropathic pain after brachial plexus root avulsion in rats

BackgroundBrachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps muscles, leading to the loss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proven to exert neuroprotective and anti-inflammatory effects on various disorders of the nervous system. Thus, the present study mainly focused on the influence of NAG on motor and sensory recovery after BPRA in rats and the underlying mechanisms.MethodsMale adult Sprague Dawley (SD) rats were subjected to BPRA and reimplantation surgery and subsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and the mechanical pain threshold of the affected forelimb. The morphological appearance of the spinal cord, musculocutaneous nerve, and biceps brachii was assessed by histological staining. Quantitative real-time PCR (qRT‒PCR) was used to measure the mRNA levels of remyelination and regeneration indicators in myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the spinal cord anterior horn were measured using Western blotting.ResultsNAG significantly accelerated the recovery of motor function in the injured forelimbs, enhanced motoneuronal survival in the anterior horn of the spinal cord, inhibited the expression of proinflammatory cytokines and pyroptosis pathway factors, facilitated axonal remyelination in the myocutaneous nerve and alleviated atrophy of the biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA.ConclusionNAG promotes functional motor recovery and alleviates neuropathic pain by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for the use of NAG as a novel treatment for BPRA.

Prespinal Versus Conventional Hemicontralateral C7 Nerve Transfer in the Treatment of Total Brachial Plexus Roots Avulsion Injuries: A Retrospective Study With a Minimum Follow-Up Period of 4 Years

Contralateral C7 (CC7)-to-median nerve transfer has been commonly used to restore hand function in brachial plexus injury. To shorten the nerve graft, the prespinal route was described and achieved direct coaptation when combined with humeral shortening osteotomy. The limb was positioned at 0° shoulder abduction and neutral head position. Given our concern about donor-site morbidity when harvesting the whole CC7 nerve and tension across the neurorrhaphy site after mobilization, we aimed to describe our modified prespinal route and compare its outcomes and complications with the conventional hemi-CC7 transfer. From 2004 to 2014, 39 patients with preganglionic total brachial plexus root avulsion injuries, with a minimum of 4 years of follow-up, were included. Overall, 20 and 19 patients underwent the conventional hemi-CC7-to-median nerve and hemi-CC7-to-lower trunk (LT) transfer through the modified prespinal route, respectively. The modified prespinal route was combined with bilateral clavicle shortening osteotomy to achieve direct coaptation to the LT at 45° shoulder abduction. The modified prespinal route showed the median period to achieve ≥M3 hand grip assessed in clinical follow-up was shorter (26.5 months vs 45.5 months), and a higher proportion of patients achieved ≥M3 hand grip recovery (63% vs 30%). One patient experienced symptomatic phrenic nerve injury; however, the hemidiaphragm fully recovered after 6 months. The long-term donor-site complication rate was 2.6%, including one sensory abnormality, and no permanent donor-site weakness after hemi-CC7 harvesting was observed. The modified prespinal route combined with clavicle osteotomy allowed direct coaptation to the LT and did not require head immobilization. It may allow a higher proportion of patients to achieve ≥M3 hand grip more quickly than conventional hemi-CC7 transfer. Therapeutic IV.

Post-Traumatic Brachial Plexus Root Avulsion: A Case Report

Root avulsion corresponds to the tearing of the roots of the spinal cord by stretching during a trauma. The most incriminated etiologies are road accidents and obstetric trauma. It results clinically in total or partial paralysis of the limb concerned or neuropathic pain. MRI is the key diagnostic test. Here we report a case of post-traumatic brachial plexus root avulsion in a 61-year-old patient following a road accident. The MRI of the cervical plexus, performed one month after the trauma, revealed a pre-foraminal fluid-like lesion on the left next to the D1 conjugation hole, suggestive of a pseudomeningocele. MRI is the key diagnostic imaging tool. In fact, it establishes the lesion topography, whether pre or post-nodal, and enables the search for associated lesions.

MiR-506-3p Relieves Neuropathic Pain following Brachial Plexus Avulsion via Mitigating Microglial Activation through Targeting the CCL2-CCR2 Axis

Neuroinflammation results in neuropathic pain (NP) following brachial plexus avulsion (BPA). This research was designed for investigating the function of miR-506-3p in BPA-induced NP. A total brachial plexus root avulsion model was produced in adult rats as well as IL-1β-treated motoneuron-like NSC-34 cells and the LPS-treated microglia cell line BV2 for in vivo and in vitro experiments, respectively. RT-PCR and Western blot were performed to detect the profiles of miR-506-3p, CCL2 and CCR2, NF-κB, FOXO3a, TNF-α, IL-1β, and IL-6 in cells or the spinal cord close to the tBPI lesion. Neuronal apoptosis was evaluated by immunohistochemistry in vivo. CCK8, TUNEL staining, and the lactic dehydrogenase kit were adopted for the evaluation of neuronal viability or damage in vitro. RNA immunoprecipitation and dual luciferase reporter gene assays analyzed the targeted association between miR-506-3p and CCL2. As shown by the data, miR-506-3p was vigorously less expressed, while CCL2-CCR2, NF-κB TNF-α, IL-1β, and IL-6 were upregulated in the spinal cord with tBPI. Overexpression of miR-506-3p attenuated neuronal apoptosis and microglial inflammation. Mechanistically, CCL2 was a downstream target of miR-506-3p. Upregulating miR-506-3p dampened CCL2-CCR2 and NF-κB activation in the spinal cord and microglia. miR-506-3p had neuroprotective and inflammation-fighting functions in the tBPI rat model via CCL2/CCR2/NF-κB axis.

Motor neuron survival is associated with reduced neuroinflammation and increased autophagy after brachial plexus avulsion injury in aldose reductase-deficient mice

Brachial plexus root avulsion (BPRA) is frequently caused by high-energy trauma including traffic accident and birth trauma, which will induces massive motoneurons (MNs) death as well as loss of motor and sensory function in the upper limb. The death of MNs is attributed to energy deficiency, neuroinflammation and oxidative stress at the injured ventral horn of spinal cord triggered by BPRA injury. It has been reported which aldose reductase (AR), an endogenous enzyme that catalyzes fructose synthesis, positively correlates with the poor prognosis following cerebral ischemic injury, diabetic retinopathy and diabetic peripheral neuropathy. However, the role of AR in BPRA remains unknown. Herein, we used a mouse model and found that in the spinal cord of BPRA mice, the upregulation of AR correlated significantly with (1) an inactivated SIRT1–AMPK–mTOR pathway and disrupted autophagy; (2) increased byproducts accumulation of lipid peroxidation metabolism and neuroinflammation; and (3) increased MNs death. Furthermore, our results demonstrated the role of AR in BPRA injury whereby the absence of AR (AR knockout mice, AR−/−) prevented the hyper-neuroinflammation and disrupted autophagy as well as motor neuron death caused by BPRA injury. Finally, we further demonstrate that AR inhibitor epalrestat is neuroprotective against BPRA injury by increasing autophagy level, alleviating neuroinflammation and rescuing MNs death in mice. Collectively, our data demonstrate that the AR upregulation in the spinal cord is an important factor contributing to autophagy disruption, neuroinflammation and MNs death following brachial plexus roots avulsion in mice. Our study also provides a promising therapy drug to assist re-implantation surgery for the treatment of BPRA.

(-)-Epigallocatechin Gallate Attenuates Spinal Motoneuron Death Induced by Brachial Plexus Root Avulsion in Rats.

Recent studies have indicated that epigallocatechin gallate (EGCG) benefits a variety of neurological insults. This study was performed to investigate the neuroprotective effect of EGCG after brachial plexus root avulsion in SD rats. One hundred twenty SD rats were randomized into the following three groups: an EGCG group, an Avulsion group, and a Sham group. There were 40 rats in each group. EGCG (100 mg/kg, i.p.) or normal saline was administered to rats immediately following the injuries. The treatment was continued from day 1 to day 7, and the animals were sacrificed on days 3, 7, 14, and 28 post-surgery for the harvesting of spinal cord samples for Nissl staining, immunohistochemistry (caspase-3, p-JNK, p-c-Jun), and western blot analysis (p-JNK, JNK, p-c-Jun, c-Jun). EGCG treatment caused significant increases in the percentage of surviving motoneurons on days 14 and 28 (p<0.05) compared to the control animals. On days 3 and 7 after avulsion, the numbers of caspase-3-positive motoneurons in the EGCG-treated animals were significantly fewer than in the control animals (p<0.05). The numbers of p- JNK-positive motoneurons and the ratio of p-JNK/JNK were no significant differences between the Avulsion group and the EGCG-treated group after injury at any time point. The numbers of p-c-Jun-positive motoneurons and the ratio of p-c-Jun/c-Jun were significantly lower in the EGCG-treated group compared with the Avulsion group at 3d and 7d after injury (p<0.05). Our results indicated that motoneurons were protected by EGCG against the cell death induced by brachial plexus root avulsion, and this effect was correlated with inhibiting c-Jun phosphorylation.

Analysis of Results of Contralateral Hemi-C7 Root Used for Restoring Hand Function in Global Birth Brachial Plexus Palsy

To analyze the outcome of the use of contralateral hemi-C7 for the restoration of hand function in patients with birth brachial plexus global palsy. From 2004 to 2017, 19 infants with Narakas types III and IV birth brachial plexus palsy underwent transfer of contralateral hemi-C7 (posterior division of the contralateral C7 root) to the lower trunk or medial cord on the affected side. All the patients were evaluated for shoulder function using the Gilbert and Mallet scores, elbow flexion using the modified Medical Research Council score for children, and hand function using the Raimondi score. After the surgery, the children were followed-up at 3-month intervals for the first year and6-month intervals thereafter. Hand function achieving Raimondi scores of 3-5 was considered a useful outcome. The patients were followed-up for a mean duration of 88 months, with a minimum of 35 and a maximum of 192 months of follow-up. All patients attained a Gilbert score of ≥3, whereas 9 patients attained a score of ≥4. Similarly, all patients attained a minimum aggregate Mallet score of 15, and 9 patients attained a score of ≥20. All patients attained a modified Medical Research Council score of ≥3, used for assessing elbow flexion. Useful hand function was attained in 73% (14/19) of the cases (a Raimondi score of ≥3). There was no clinically recorded deficit on the donor side. Contralateral hemi-C7 transfer in infants with brachial plexus root avulsions helped regain useful hand function in 73% (14/19) of the children treated. Therapeutic IV.

PLGA-PEG-PLGA hydrogel with NEP1-40 promotes the functional recovery of brachial plexus root avulsion in adult rats.

Adult brachial plexus root avulsion can cause serious damage to nerve tissue and impair axonal regeneration, making the recovery of nerve function difficult. Nogo-A extracellular peptide residues 1-40 (NEP1-40) promote axonal regeneration by inhibiting the Nogo-66 receptor (NgR1), and poly (D, L-lactide-co-glycolide)-poly (ethylene glycol)-poly (D, L-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel can be used to fill in tissue defects and concurrently function to sustain the release of NEP1-40. In this study, we established an adult rat model of brachial plexus nerve root avulsion injury and conducted nerve root replantation. PLGA-PEG-PLGA hydrogel combined with NEP1-40 was used to promote nerve regeneration and functional recovery in this rat model. Our results demonstrated that functional recovery was enhanced, and the survival rate of spinal anterior horn motoneurons was higher in rats that received a combination of PLGA-PEG-PLGA hydrogel and NEP1-40 than in those receiving other treatments. The combined therapy also significantly increased the number of fluorescent retrogradely labeled neurons, muscle fiber diameter, and motor endplate area of the biceps brachii. In conclusion, this study demonstrates that the effects of PLGA-PEG-PLGA hydrogel combined with NEP1-40 are superior to those of other therapies used to treat brachial plexus nerve root avulsion injury. Therefore, future studies should investigate the potential of PLGA-PEG-PLGA hydrogel as a primary treatment for brachial plexus root avulsion.

Artemisinin Facilitates Motor Function Recovery by Enhancing Motoneuronal Survival and Axonal Remyelination in Rats Following Brachial Plexus Root Avulsion.

Artemisinin (ART), a well-known antimalarial medicine originally isolated from the plant Artemisia annua, exerts neuroprotective effects in the nervous system owing to an antioxidant effect. Here, we determined whether ART is capable of inhibiting the oxidative stress to enhance motoneuronal (MN) survival to promote motor function recovery of rats following brachial plexus root avulsion (BPRA) with reimplantation surgery. Rats following BPRA and reimplantation were subcutaneously injected with 500 μL of PBS or 16 mg/mL ART once daily for 7 days after surgery. Terzis grooming test (TGT), histochemical staining, real-time polymerase chain reaction, and Western blot were conducted to determine the recovery of motor function of the upper limb, the survival rate of MNs, the oxidative stress levels in the ventral horn of the spinal cord, the morphology of abnormal musculocutaneous nerve fibers, the remyelination of axons in musculocutaneous nerves, and the degree of bicep atrophy. ART significantly increased TGT score, improved the survival of MNs, inhibited the oxidative stress, ameliorated the abnormal morphology of fibers in the musculocutaneous nerve, promoted the remyelination of axons, and alleviated muscle atrophy. Take together, ART can improve the survival of MNs and axonal remyelination to promote the motor function recovery via inhibiting oxidative stress, suggesting that ART may represent a new approach to the therapy of spinal root avulsion.

Long-term functional recovery in C5-C6 avulsions treated with distal nerve transfers

ABSTRACT Background In patients suffering from traction lesions of the brachial plexus, complete C5 and/or C6 root avulsion patients with C7 root preservation are relatively uncommon occurrences, but represent excellent candidates for surgical treatment, with satisfactory results. Shoulder abduction and extra-rotation, elbow flexion and forearm supination are lost functions restorable with surgical treatment. Methods This single-center, prospective observational study involved a series of 27 young adults with C5 and/or C6 root complete avulsion and C7 preservation, which underwent surgical repair with double or triple nerve transfer. Results Patients recovered a useful elbow flexion. Electromyographic and clinical signs of biceps reinnervation were observed in each UN-MC nerve transfer. The abduction strength recovery was M5 in 10 patients, M4 in 14 patients and M3 in 3 patients. The external rotation strength recovery was M5 in 4 patients, M4 in 18 patients, M3 in 3 patients and M2 in 2 patients. The elbow flection strength was M5 in 5 patients, M4 in 15 patients and M3 in 7 patients. Elbow extension was preserved in all cases. Conclusions The concept of ‘peripheral rewiring procedures’ represents an advance in the repair of the peripheral nerve injuries. Triple nerve transfer can be nowadays considered a standard treatment for isolated C5-C6 avulsions. We report our experience with the second-biggest casuistry in the literature on patients treated with this technique. We consider our outcome concerning functional recovery to be satisfying and comparable to data reported in the literature.

Long-Term Suppression of c-Jun and nNOS Preserves Ultrastructural Features of Lower Motor Neurons and Forelimb Function after Brachial Plexus Roots Avulsion.

Brachial plexus root avulsions cause debilitating upper limb paralysis. Short-term neuroprotective treatments have reported preservation of motor neurons and function in model animals while reports of long-term benefits of such treatments are scarce, especially the morphological sequelae. This morphological study investigated the long-term suppression of c-Jun- and neuronal nitric oxide synthase (nNOS) (neuroprotective treatments for one month) on the motor neuron survival, ultrastructural features of lower motor neurons, and forelimb function at six months after brachial plexus roots avulsion. Neuroprotective treatments reduced oxidative stress and preserved ventral horn motor neurons at the end of the 28-day treatment period relative to vehicle treated ones. Motor neuron sparing was associated with suppression of c-Jun, nNOS, and pro-apoptotic proteins Bim and caspases at this time point. Following 6 months of survival, neutral red staining revealed a significant loss of most of the motor neurons and ventral horn atrophy in the avulsed C6, 7, and 8 cervical segments among the vehicle-treated rats (n = 4). However, rats that received neuroprotective treatments c-Jun JNK inhibitor, SP600125 (n = 4) and a selective inhibitor of nNOS, 7-nitroindazole (n = 4), retained over half of their motor neurons in the ipsilateral avulsed side compared. Myelinated axons in the avulsed ventral horns of vehicle-treated rats were smaller but numerous compared to the intact contralateral ventral horns or neuroprotective-treated groups. In the neuroprotective treatment groups, there was the preservation of myelin thickness around large-caliber axons. Ultrastructural evaluation also confirmed the preservation of organelles including mitochondria and synapses in the two groups that received neuroprotective treatments compared with vehicle controls. Also, forelimb functional evaluation demonstrated that neuroprotective treatments improved functional abilities in the rats. In conclusion, neuroprotective treatments aimed at suppressing degenerative c-Jun and nNOS attenuated apoptosis, provided long-term preservation of motor neurons, their organelles, ventral horn size, and forelimb function.

Pain Relief Dependent on IL-17-CD4+ T Cell-β-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy.

Background and purposeNeuropathic pain is the typical symptom of brachial plexus root avulsion (BPRA), and no effective therapy is currently available. Electroacupuncture (EA), as a complementary and alternative therapy, plays a critical role in the management of pain-associated diseases. In the present study, we aimed to reveal the peripheral immunological mechanism of EA in relieving the pain of BPRA through the IL-17–CD4+ T lymphocyte–β-endorphin axis.MethodsAfter receiving repeated EA treatment, the pain of BPRA in rats along with the expressions of a range of neurotransmitters, the contents of inflammatory cytokines, and the population of lymphocytes associated were investigated. CD4+ T lymphocytes were either isolated or depleted with anti-CD4 monoclonal antibody. The titers of IL-17A, interferon-γ (IFN-γ), and β-endorphin were examined. The markers of T lymphocytes, myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), macrophages, and natural killer (NK) cells were assessed. The activation of the nuclear transcription factor κB (NF-κB) signaling pathway was tested.ResultsThe pain of BPRA was significantly relieved, and the amount of CD4+ T lymphocytes was increased after EA treatment. The release of β-endorphin was up-regulated with the up-regulation of IL-17A in CD4+ T lymphocytes. The titer of IL-17A was enhanced, leading to an activated NF-κB signaling pathway. The release of β-endorphin and the analgesic effect were almost completely abolished when CD4+ T lymphocytes were depleted.ConclusionWe, for the first time, showed that the neuropathic pain caused by BPRA was effectively relieved by EA treatment via IL-17–CD4+ T lymphocyte–β-endorphin mediated peripheral analgesic effect, providing scientific support for EA clinical application.

Cytokine profile and glial activation following brachial plexus roots avulsion injury in mice

Inflammation and tissue infiltration by various immune cells play a significant role in the pathogenesis of neurons suffering the central nervous systems diseases. Although brachial plexus root avulsion (BPRA) leads to dramatic motoneurons (MNs) death and permanent loss of function, however, the knowledge gap on cytokines and glial reaction in the spinal cord injury is still existing. The current study is sought to investigate the alteration of specific cytokine expression patterns of the BPRA injured spinal cord during an acute and subacute period. The cytokine assay, transmission electron microscopy, and histological staining were utilized to assess cytokine network alteration, ultrastructure morphology, and glial activation and MNs loss within two weeks post-injury on a mouse unilateral BPRA model. The BPRA injury caused a progressively spinal MNs loss, reduced the alpha-(α) MNs synaptic inputs, whereas enhanced glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule-1 (IBA-1), F4/80 expression in ipsilateral but not the contralateral spinal segments. Additionally, cytokine assays revealed BPRA significantly altered the level of CXCL1, ICAM1, IP10, MCP-5, MIP1-α, and CD93. Notably, the elevated MIP1-α was mainly expressed in the injured spinal MNs. While the re-distribution of CD93 expression, from the cytoplasm to the nucleus, occasionally occurred at neurons of the ipsilateral spinal segment after injury. Overall, these findings suggest that the inflammatory cytokines associated with glial cell activation might contribute to the pathophysiology of the MNs death caused by nerve roots injury.

DREZotomy in the management of post brachial plexus root avulsion neuropathic pain: fMRI correlates for pain relief

Background Deafferentiation pain following brachial plexus root avulsion has been documented to be severe enough to affect activities of daily living in patients. Microsurgical DREZotomy is known to alleviate the symptoms by decreasing the afferent signals transmitted from the spinal cord to sensory cortex. Objectives To document and analyse the effectiveness of DREZotomy and to evaluate the role of ‘sensory cortex’ in the cause and relief of dysesthetic pain, using fMRI. Materials and methods This was a prospective study conducted between 2010 and 2016 and included all patients who underwent DREZotomy for dysesthetic pain following traumatic brachial plexus injury (TBPI). Patients were evaluated both preoperatively and postoperatively with Visual Analogue Scale(VAS), Hospital Anxiety and Depression score (HADS) and SF36 questionnaire and effectiveness of surgery was assessed. Functional magnetic resonance imaging (fMRI) of the brain in resting state was performed before and after surgery and was also compared with controls. Patients underwent standard microsurgical DREZotomy from C5 to D1. Postoperative assessment was done at 6 weeks and 6 months following surgery. Results Our series had 18 patients aged between 22 and 63 years. RTA was the most common cause of injury. There was significant decrease in pain at 6 months follow up compared to pre-operative values as assessed by VAS, HADS, SF36 questionnaire. fMRI analysis revealed cluster activations in the sensory, motor cortex and in the right cingulate gyrus in the preoperative group which was higher than in normal controls. In the postoperative group, the size of the resting state activation was significantly reduced. Conclusion DREZotomy is an effective procedure for TBPI patients. We hypothesize that these fMRI findings reflect the cortical reorganization that occurs not only after injury but also following successful surgery which explains the cause and relief of dyesthetic pain.

Trehalose protects motorneuron after brachial plexus root avulsion by activating autophagy and inhibiting apoptosis mediated by the AMPK signaling pathway.

Brachial plexus root avulsion (BPRA) is one of the most serious injuries of the upper extremity, which requires more effective treatment. Trehalose, a natural disaccharide, has reported to has a protective effect in neurodegenerative diseases. However, the effective effects and mechanism of trehalose on BPRA are still unclear. BPRA rat model were established, and then effects of trehalose on BPRA were investigated. TBHP-treated NSC34 cells with or without trehalose treatment were used for mechanism studies by Western blotting, Immunofluorescence and Flow cytometry analysis. Trehalose elevated the survival of motor neurons in rats after BPRA, suggesting a protective role of trehlose on BPRA. Trehalose treatment in rats after BPRA enhanced the autophage and thus inhibited apoptosis compared with rats in Vehicle group. Moreover, in TBHP-treated NSC34 cells, trehalose promoted the expression of autophage-related markers (LC3 and Beclin-1), concomitant with decreased levels of apoptosis. In vitro mechanism study indicated that the regulations of trehalose on autophage and apoptosis were via the AMPK-ULK1 pathway. Trehalose protects injured MNs by enhancing autophage and inhibiting apoptosis, which demonstrating the essential role of trehalose in the prevention and treatment of BPRA.

Surgical Technique of Xu's CC7 Procedure "Contralateral C7 to C7 Cross Nerve Transfer Through a Trans Longus Colli, Prespinal Route for Treating Spastic Arm".

The contralateral C7 transfer has been used for the treatment of brachial plexus root avulsion since 1986, and several modifications of this surgery have been described. Previous trial has verified the safety and effectiveness of the contralateral C7 to C7 cross nerve transfer for patients with longstanding spastic paralysis due to cerebral injuries, including stroke, traumatic brain injury, or cerebral palsy. However, the procedures for the surgery were not introduced in detail, with only rough descriptions. To introduce and promote the Xu's CC7 procedure (contralateral C7 to C7 cross nerve transfer through a trans longus colli, prespinal route). The renewed procedures were elaborated step by step, and the tips and tricks were clarified by case illustration in detail. Briefly, a modified trans longus colli, prespinal route was created, allowing the displaced C7 nerve to pass through the channel safely at the shortest distance. Tension-free anastomosis of the bilateral C7 nerves was achieved via the Xu's CC7 procedure with less surgical trauma while reducing the surgery time, postoperative recovery time, and nerve regeneration time. The Xu's CC7 procedure is a safer and more efficient technique for contralateral C7 to C7 cross nerve transfer. The detailed description in this article provides meaningful information for surgeons interested in the procedure.

Upregulation of JHDM1D-AS1 alleviates neuroinflammation and neuronal injury via targeting miR-101-3p-DUSP1 in spinal cord after brachial plexus injury

BackgroundNeuroinflammation in the spinal cord following acute brachial plexus injury (BPI) remains a vital cause that leads to motor dysfunction and neuropathic pain. In this study, we aim to explore the role of long non-coding RNA JHDM1D antisense 1 (JHDM1D-AS1) in mediating BPI-induced neuroinflammation and neuronal injury. MethodsA total brachial plexus root avulsion (tBPRA) model in adult rats and IL-1β-treated motor neuron-like NSC-34 cells and LPS-treated microglia cell line BV2 were conducted for in vivo and in vitro experiments, respectively. The expressions of JHDM1D-AS1, miR-101-3p and DUSP1, p38, NF-κB, TNF-α, IL-1β, and IL-6 were detected by RT-PCR and western blot seven days after tBPI. Immunohistochemistry (IHC) was used to detect neuronal apoptosis. CCK8 assay, Tunel assay and LDH kit were used for the detection of neuronal injury. The targeted relationships between JHDM1D-AS1 and miR-101-3p, miR-101-3p and DUSP1 were verified by RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assay. ResultsWe found significant downregulated expression of JHDM1D-AS1 and DUSP1 but upregulated expression of miR-101-3p in the spinal cord after tBPI. Overexpression of JHDM1D-AS1 had a prominent neuroprotective effect by suppressing neuronal apoptosis and microglial inflammation through reactivation of DUSP1. Further exploration revealed that JHDM1D-AS1 may act as a competitive endogenous RNA targeting miR-101-3p, which bound on the 3′UTR of DUSP1 mRNA. In addition, overexpression of miR-101-3p could reverse the neuroprotective effects of JHDM1D-AS1 upregulation by blocking DUSP1. ConclusionsJHDM1D-AS1 exerted neuroprotective and anti-inflammatory effects in a rat model of tBPI by regulating miR-101-3p/DUSP1 axis.

Berberine enhances L1 expression and axonal remyelination in rats after brachial plexus root avulsion.

Background and PurposeEnhanced remyelination of the regenerated axons results in functional re‐innervation and improved functional motor recovery after brachial plexus root avulsion (BPRA). The neural cell adhesion molecule L1 (L1CAM, L1) regulates myelination and promotes regeneration after acute injury in the nervous system. Berberine (BBR) can exert neuroprotective roles against the lesion. Herein, we investigated whether berberine (BBR) can affect the expression of L1 and enhance the axonal remyelination in rats following BPRA.MethodsThe surgical procedures were performed to build the rat brachial plexus avulsion and re‐implantation model, and then, the rats were treated with BBR. After the rehabilitation for 12 weeks, the musculocutaneous nerves were collected for quantitative real‐time PCR, Western blot analysis, and histochemical and immunofluorescence staining.ResultsWe observed that, BBR treatment ameliorated the abnormal musculocutaneous nerve fibers morphology, up‐regulated the L1 expression, increased the myelination‐related genes, decreased the differentiated‐associated genes, and up‐regulated the phosphorylation of ERK.ConclusionThese results suggest that BBR may enhance L1 expression and promote axonal remyelination after spinal root avulsion.

BCI training to move a virtual hand reduces phantom limb pain: A randomized crossover trial.

ObjectiveTo determine whether training with a brain–computer interface (BCI) to control an image of a phantom hand, which moves based on cortical currents estimated from magnetoencephalographic signals, reduces phantom limb pain.MethodsTwelve patients with chronic phantom limb pain of the upper limb due to amputation or brachial plexus root avulsion participated in a randomized single-blinded crossover trial. Patients were trained to move the virtual hand image controlled by the BCI with a real decoder, which was constructed to classify intact hand movements from motor cortical currents, by moving their phantom hands for 3 days (“real training”). Pain was evaluated using a visual analogue scale (VAS) before and after training, and at follow-up for an additional 16 days. As a control, patients engaged in the training with the same hand image controlled by randomly changing values (“random training”). The 2 trainings were randomly assigned to the patients. This trial is registered at UMIN-CTR (UMIN000013608).ResultsVAS at day 4 was significantly reduced from the baseline after real training (mean [SD], 45.3 [24.2]–30.9 [20.6], 1/100 mm; p = 0.009 < 0.025), but not after random training (p = 0.047 > 0.025). Compared to VAS at day 1, VAS at days 4 and 8 was significantly reduced by 32% and 36%, respectively, after real training and was significantly lower than VAS after random training (p < 0.01).ConclusionThree-day training to move the hand images controlled by BCI significantly reduced pain for 1 week.Classification of evidenceThis study provides Class III evidence that BCI reduces phantom limb pain.