Root Avulsion Research Articles

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.

Transfer of the phrenic nerve to musculocutaneous nerve via sural nerve graft after total brachial plexus injury

A middle age male presented a right total brachial plexus injury after motorcycle fall one year ago. Subsequent electromyographic evaluation was consistent withC5, C6, C7, C8 and T1 root avulsion. The patient was submitted to a right transfer of thephrenic nerve to musculocutaneous nerve , using rural nerve graft.

Brachial plexus paralysis associated with traumatic asphyxia

Traumatic injuries are the most common cause of brachial plexus lesions in children and adults. There are many causes of brachial plexus injuries such as accidents, falls and prolonged pressure. Traumatic asphyxia (TA) is a rare but serious clinical syndrome. Rarely, brachial plexus lesion may develop after TA and it is extremely rare in children. The cause of brachial plexus injury in patients without posttraumatic nerve root avulsion has not yet been fully explained. In this case report, we present the case of a child with neurological damage following TA which is very rare in the literature.

Stable Lateral Meniscal Posterior Root Tears Left In Situ at Time of Anterior Cruciate Ligament Reconstruction Are of Minimal Long-Term Clinical Detriment

The purpose of this study was to compare long-term patient-reported outcomes in patients undergoing anterior cruciate ligament (ACL) reconstruction with untreated stable lateral meniscal posterior root (LMPR) tears to those with an intact meniscus. Four hundred ninety-two subjects were followed for a minimum of 15-years post-ACL reconstruction and evaluated by an International Knee Documentation Committee questionnaire. The integrity of the meniscus was classified at surgery. Patients were grouped as either untreated injury to LMPR "with stable tear" (WST) group (n= 52) or intact lateral meniscus "no tear" (NT) group (n= 440). WST group included tears where those with a root avulsion within 9 mm of insertion and parrot beak tears with the integrity of the root attachment maintained. Outcomes were compared between groups. ACL graft rupture occurred in 10% in the WST group and in 11% in the NT group (P= .78). For participants with an intact graft (n= 440), the mean International Knee Documentation Committee scores were 82, in the WST group, and 87, in the NT group (P= .03), with a small effect size of .32. The WST group had a worse mean pain severity score (P= .04) and higher frequency of pain (P= .03) than the NT group, but the effect size was small (P < 0.3). There was no difference in the overall knee function (P= .209) or International Knee Documentation Committee activity level (P= .882). There was no adverse clinical outcome to leaving a stable LMPR tear in situ at the time of ACL reconstruction. LMPR tears left in situ were of minimal clinically significant long-term detriment, with outcomes similar to having an intact meniscus. There is an innate desire to fix the broken, but posterior meniscal root avulsions and stable parrot beak tears within 9 mm of insertion may not require intervention. At 15 years postinjury, most patients with a stable tear left in situ continue to enjoy an active lifestyle with a pain-free knee. Level III, retrospective comparative study.

The effects of different repair methods for a posterior root tear of the lateral meniscus on the biomechanics of the knee: a finite element analysis

PurposeTo explore the impact of different repair methods for a lateral meniscus posterior root tear on the biomechanics of the knee joint using finite element analysis.MethodsFinite element models of a healthy knee were established on the basis of MRI data from a volunteer using Mimics software, and the validity of the models was tested. The changes in the contact mechanics and kinematics of these finite element models under different repair approaches were then analyzed and compared.ResultsThe normal meniscus had the maximum joint contact area, the minimum contact pressure, and the minimum contact stress. When total meniscectomy of the lateral meniscus was performed, the lateral compartment had the minimum joint contact area, the maximum contact pressure and the maximum contact stress. When complete avulsions of the posterior root of the lateral meniscus occurred, the maximum values of contact pressure and contact stress were between those of an intact meniscus and those of a meniscus treated with total meniscectomy. Lateral meniscal root attachment reconstruction by the single-stitch and double-stitch techniques resulted in a significant decrease in joint contact pressure and contact stress, leading to values comparable to those of a normal knee joint, and the double-stitch technique performed better than the single-stitch technique.ConclusionsRepair surgery for lateral meniscal posterior root avulsions can effectively restore the contact mechanics and kinematics of the knee joint, and the double-stitch technique can result in better clinical outcomes than the single-stitch technique.

MRI evaluation of nerve root avulsion in neonatal brachial plexus palsy: understanding the presence of isolated dorsal/ventral rootlet disruption.

The evaluation, treatment, and prognosis of neonatal brachial plexus palsy (NBPP) continues to have many areas of debate, including the use of ancillary testing. Given the continued improvement in imaging, it is important to revisit its utility. Nerve root avulsions have historically been identified by the presence of pseudomeningoceles or visible ruptures. This "all-or-none" definition of nerve root avulsions has many implications for the understanding and management of NBPP, especially as characterization of the proximal nerve root as a potential donor remains critical. This study examined the ability of high-resolution MRI to more specifically define the anatomy of nerve root avulsions by individually examining the ventral and dorsal rootlets as they exit the spinal cord. This is a retrospective review of patients who had undergone brachial plexus protocol MRI for clinical evaluation of NBPP at a single institution. Each MR image was independently reviewed by a board-certified neuroradiologist, who was blinded to both established diagnosis/surgical findings and laterality. Each dorsal and ventral nerve rootlet bilaterally from C5 to T1 was evaluated from the spinal cord to its exit in the neuroforamen. Each rootlet was classified as avulsed, intact, or undeterminable. Sixty infants underwent brachial plexus protocol MRI from 2010 to 2018. All infants were included in this study. Six hundred individual rootlets were analyzed. There were 49 avulsed nerve rootlets in this cohort. Twenty-nine (59%) combined dorsal/ventral avulsions involved both the ventral and dorsal rootlets, and 20 (41%) were either isolated ventral or isolated dorsal rootlet avulsions. Of the isolated avulsion injuries, 13 (65%) were dorsal only, meaning that the motor rootlets were intact. A closer look at nerve root avulsions with MRI demonstrates a significant prevalence (approximately 41%) of isolated dorsal or ventral nerve rootlet disruptions. This finding implies that nerve roots previously labeled as "avulsed" but with only isolated dorsal (sensory) rootlet avulsion can yet provide donor fascicles in reconstruction strategies. A majority (99%) of the rootlets can be clearly visualized with MRI. These findings may significantly impact the clinical understanding of neonatal brachial plexus injury and its treatment.

Traumatic Brachial Plexus Palsy in Children: Long-Term Outcome and Strategy of Reconstruction.

Traumatic brachial plexus injuries in children represent a definite spectrum of injuries between adult and neonatal brachial plexus injuries. Their characteristics have been scarcely reported in the literature. The priority of functional restoration is not clear. In total, 52 children with surgically treated traumatic brachial plexus injuries, excluding Erb's palsy, were reviewed after a minimum follow-up of 2 years. All children except nine were males, with an average age at surgery of 8 years. Forty-five children had exclusive supraclavicular plexus injuries. Twenty-one of them (46%) had two or more root avulsions. Seven children (13.5%) had infraclavicular plexus injuries. Time from trauma to surgery varied from 1 to 15 months (mean = 4.7 months). Extraplexal neurotization was the most common surgical technique used. Shoulder abduction and external rotation were restored to an average of 83 and 26 degrees, respectively. Elbow flexion and extension were restored to grade ≥3 in 96 and 91.5% of cases, respectively. Finger flexion and extension were restored to grade ≥4 in 29 and 32% of cases, respectively. Wrist flexion and extension were restored to grade ≥4 in 21 and 27% of cases, respectively. Results of neurotization were superior to those of neurolysis and nerve grafting. Among the 24 children with insensate hands, 20 (83.3%) recovered S3 sensation, 3 recovered S2, and 1 recovered S1. No case complained of neuropathic pain. Functional recovery correlated negatively but insignificantly with the age at surgery and time from injury to surgery. Brachial plexus injuries in children are associated with a high incidence root avulsions and no pain. Neurotization is frequently required and the outcome is not significantly affected by the delay in surgery. In total plexus injuries, some useful hand function can be restored, and management should follow that of obstetric palsy and be focused on innervating the medial cord.

A stimulating life and career – an obituary for Professor Gerta Vrbová

A stimulating life and career – an obituary for Professor Gerta Vrbová

Surgical Reconstruction of Isolated Upper Trunk Brachial Plexus Birth Injuries in the Presence of an Avulsed C5 or C6 Nerve Root.

Avulsion of either the C5 or C6 root with intact middle and lower trunks in brachial plexus birth injury is rare. In these cases, only 1 proximal root is available for intraplexal reconstruction. The purpose of the present study was to determine the outcomes of these patients when single-root reconstruction was balanced across the anterior and posterior elements of the upper trunk. We performed a retrospective cohort study of prospectively collected data for patients with brachial plexus birth injury who underwent primary nerve reconstruction between 1993 and 2014. Patients were included who had isolated upper-trunk injuries with intact middle and lower trunks. The study group had avulsion of either the C5 or C6 root. The control group had neuroma-in-continuity or ruptures of the upper trunk. Outcomes were assessed with use of the Active Movement Scale and the Brachial Plexus Outcome Measure. The Wilcoxon signed-rank test was utilized to evaluate changes across treatment. Ten patients with brachial plexus birth injury were included in the avulsion cohort. Surgical reconstruction entailed neuroma resection and nerve grafting from the single available root balanced across all distal targets with or without spinal accessory-to-suprascapular nerve transfer. Significant improvements were observed across treatment for both the avulsion and control groups in terms of shoulder abduction, shoulder flexion, external rotation, elbow flexion, and supination. At a mean follow-up of 54.5 ± 8.8 months, patients in the avulsion group achieved Active Movement Scale scores of 6.8 ± 0.4 for elbow flexion and 6.5 ± 0.9 for shoulder flexion and abduction, with lesser recovery observed in external rotation (3.3 ± 2.8). All patients available for Brachial Plexus Outcome Measure assessments demonstrated functional movement. In the setting of avulsion of 1 upper-trunk root, nerve reconstruction by grafting of the upper trunk from the other upper-trunk root provides improved movement, high Active Movement Scale scores, and satisfactory function according to the Brachial Plexus Outcome Measure. These data provide support for a strategy that ensures the entire upper trunk is adequately reconstructed in the setting of upper-trunk lesions. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Multi-Ligament Knee Injury with Concomitant Tibial Tubercle Fracture: A Challenging Case Report and Review of the Pertinent Literature

Background: Multi-ligament knee injury (MLKI) combined with a comminuted tibial tubercle avulsion fracture in the literature has been reported as a very rare condition. To the best of our knowledge, there was no case report of this condition associated with open proximal tibia fractures. Case Report: A 32-year-old man was referred to our center, with a comminuted tibial tubercle fracture, patella alta, fracture of the tibia at the proximal meta-diaphyseal junction, a Segond fracture, and proximal tibiofibular dislocation on X-ray images. Further assessment of intra-articular pathologies was performed during the operation and complete tear of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) tear were identified. Radial tear of the body and anterior root avulsion of medial meniscus were also noted. All of the extra-articular and intra-articular injuries were addressed surgically, except ACL and PCL tear, which were postponed to a second stage. Proximal tibiofibular dislocation was not approached surgically. The rehabilitation protocol included 6 weeks of non-weight-bearing followed by 6 weeks of crutch-assisted partial weight-bearing ambulation, and forbidden active knee extension during the first 6 weeks and allowing the patient to perform passive flexion of the knee to 90 degrees starting from the second week. Following the rehabilitation program, the patient achieved near-full range of motion (ROM) by the end of 6 months of clinical follow-up. Conclusion: By means of our specific surgical technique and post-operative rehabilitation protocol, we led the patient with this specific condition to have fracture union and near-normal ROM by the end of 6 months.

Idiopathic superficial siderosis of the central nervous system

BackgroundRegardless of the cause of the superficial siderosis (SS) disease, which is bleeding, the source of bleeding cannot be found in some cases.Case presentationIn this article, we report two cases with idiopathic SS. Case 1 presented with bilateral hearing loss, cognitive impairment, sleep disturbances, and tremors. Case 2 presented with sensory neural hearing loss, ataxia, and spastic paraparesis. In both cases, brain MRI indicated evidence of SS. CT myelogram and SPECT with labeled RBC couldn’t help finding the source of occult bleeding.ConclusionSS is a rare central nervous system disease caused by the deposition of hemosiderin in the brain and spinal cord, which results in the progression of neurological deficits. The cause of this hemorrhage is often subarachnoid haemorrhage, intracranial surgery, carcinoma, arteriovenous malformation, nerve root avulsion, and dural abnormality. The condition progresses slowly and, by the time diagnosis is confirmed, the damage is often irreversible. In our cases, brain MRI clarified the definitive diagnosis, but we could not find the source of bleeding. SS should be considered in cases with ataxia and hearing loss, even if no source of bleeding is found.

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.

A rare case of symptomatic nonunion of avulsion fracture of the posterior medial meniscus root with concomitant posterior cruciate ligament injury

The menisci are the essential structures of the knee joint because they disperse body weight and reduce friction during the movement. An avulsion fracture of the posterior medial meniscus root, also known as meniscal ossicles, can lead to meniscal extrusion. Consequently, the medial meniscus loses its ability to absorb hoop stress. One patient presented with nonunion posterior root avulsion fracture of the medial meniscus concomitant with posterior cruciate ligament (PCL) injury. The patient underwent arthroscopic suture repair through the placement of a tibial tunnel 1 year after injury. The fracture united well, and complete recovery was achieved at the 2-year follow-up. To the best of our knowledge, this is the first report describing a posterior root avulsion fracture of the medial meniscus with concomitant PCL avulsion fracture.

Brachial plexus trauma: contralateral C7 transfer evaluation

Background and aim Root avulsion injury of brachial plexus is a serious injury. Many attempts have been made regarding contralateral transfer of C7 to restore hand function. We designed this work to evaluate efficacy of contralateral C7 (CC7) transfer in the management of avulsion root injury. Patients and methods Between 2015 and 2018, 11 patients with avulsion root injury were enrolled in the study. All of them were males. After the procedure, those patients were followed for at least 2 years to assess the effect of transfer on healthy limb function, sensory and motor recovery of the recipient nerves in the affected limb, and coordination between the healthy and affected limbs. Results It was noticed that three patients had finger and wrist flexion grade 3, whereas seven patients had flexion grade 2 and only one patient demonstrated grade 0. According to hand sensation recovery, nine patients of the group showed S2 recovery and two patients showed S1. All 11 patients included in this study have achieved good results by Elbow Mayo score system, in spite of only three patients achieving satisfactory result by Gilbert shoulder system score and eight patients had fair results. Conclusion Transfer of CC7 (total CC7 transfer) with direct repair for reconstructing limb function was? significantly better than CC7 transfer with graft.

The Problems of Meniscal Root Tears

Meniscal root tears are defined as radial tears located within 1 cm from the meniscal attachment or a bony root avulsion. This injury is biomechanically comparable to a total meniscectomy, leading to compromised hoop stresses resulting in decreased tibiofemoral contact area and increased contact pressures in the involved compartment. These changes are detrimental to the articular cartilage and ultimately lead to the development of early osteoarthritis. Surgical repair is the treatment of choice in patients without significant osteoarthritis (Outerbridge grades 3 or 4). Root repairs have been reported to improve clinical outcomes, decrease meniscal extrusion and slow the onset of degenerative changes. In this article, we describe the anatomy, biomechanics, clinical evaluation, treatment methods, outcomes, and post-operative rehabilitation for posterior meniscal root tears.

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.

GDNF Gene Therapy to Repair the Injured Peripheral Nerve.

A spinal root avulsion is the most severe proximal peripheral nerve lesion possible. Avulsion of ventral root filaments disconnects spinal motoneurons from their target muscles, resulting in complete paralysis. In patients that undergo brachial plexus nerve repair, axonal regeneration is a slow process. It takes months or even years to bridge the distance from the lesion site to the distal targets located in the forearm. Following ventral root avulsion, without additional pharmacological or surgical treatments, progressive death of motoneurons occurs within 2 weeks (Koliatsos et al., 1994). Reimplantation of the avulsed ventral root or peripheral nerve graft can act as a conduit for regenerating axons and increases motoneuron survival (Chai et al., 2000). However, this beneficial effect is transient. Combined with protracted and poor long-distance axonal regeneration, this results in permanent function loss. To overcome motoneuron death and improve functional recovery, several promising intervention strategies are being developed. Here, we focus on GDNF gene-therapy. We first introduce the experimental ventral root avulsion model and discuss its value as a proxy to study clinical neurotmetic nerve lesions. Second, we discuss our recent studies showing that GDNF gene-therapy is a powerful strategy to promote long-term motoneuron survival and improve function when target muscle reinnervation occurs within a critical post-lesion period. Based upon these observations, we discuss the influence of timing of the intervention, and of the duration, concentration and location of GDNF delivery on functional outcome. Finally, we provide a perspective on future research directions to realize functional recovery using gene therapy.