Nerve Bridge Research Articles

Biological conduits based on spider silk for reconstruction of extended nerve defects.

The availability of appropriate conduits remains an obstacle for successful reconstruction of long-distance nerve defects. In previous sheep trials, we were able to bridge 6 cm nerve gaps with nerve conduits based on spider silk fibers with full functional outcomes. Here, we describe the first application of spider silk for nerve repair inhumans. Four patients with extended nerve defects (>20 cm) underwent nerve reconstruction by interposition of conduits that were composed of spider silk fibers contained in autologous veins. The longitudinal luminal fibers (approx.2500 fibers per graft) consisted of drag line silkfrom Trichonephila spiders. All patients were evaluated between 2and 10 years postreconstruction, clinically, and byneurography. In all patients, primary wound healing and no adverse reactions to the implanted spider silk material wereobserved. Patients regained the following relevant functions: protective sensibility, full flexor function with near-normal grasp and powerful function after microvascular gracilis muscle transfer, and key grip function and gross finger flexion after additional tenodesis. One patient with sciatic nerve reconstruction developed protective sensibility of the lower leg, foot, and gait, enabling normal walking and jogging. No neuroma formation or neuropathic or chronic pain occurred in any of the patients. For patients with extended peripheral nerve defects in the extremities, use of conduits based on spider silk fibers offers the possibility of restoring sensory function and protection from neuroma. This kind of nerve bridges provides new perspectives for the reconstruction of complex and long-distance nerve defects.

Clinical analysis of transcranial facial nerve bridging with interpositional graft for the treatment of facial nerve injury

Objective:To retrospectively analyze the effectiveness of transcranial facial nerve bridging in the treatment of facial nerve dysfunction. Methods:A retrospective analysis was conducted on 27 patients with facial nerve dysfunction who underwent transcranial facial nerve bridging at the Eye, Ear, Nose, and Throat Hospital affiliated with Fudan University from 2017 to 2022. The main collected data includes the patient's age, gender, primary lesion, damaged location, interval from facial paralysis to surgery, and preoperative and postoperative House-Brackmann（HB） scale for facial nerve function. Statistical comparisons were made between the average HB level of patients before and after surgery. Results:A total of 27 patients included 17 males and 10 females. The average age of patients during surgery is（42.50±3.38） years old. Primary lateral skull base diseases include trauma（n=3）, tumors（n=22）, and infections（n=2）. The duration of facial paralysis varies from 6 months to 5 years. Statistics analysis has found that the average postoperative HB score of patients who underwent transcranial facial nerve bridging was significantly lower at（3.750 ± 0.183） compared to preoperative（4.875±0.168）. The proportion of patients with good facial nerve function increased significantly from 7.4% before surgery to 42.9% after surgery. Conclusion:Transcranial facial nerve bridging surgery with interpositional graft has a significant effect on improving facial nerve function in patients with facial nerve injury. Further research is still needed to evaluate the long-term effectiveness of this surgery, to determine the optimal patient selection criteria and postoperative rehabilitation strategies.

N-cadherin directs the collective Schwann cell migration required for nerve regeneration through Slit2/3 mediated contact inhibition of locomotion.

Collective cell migration is fundamental for the development of organisms and in the adult, for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact inhibition of locomotion (CIL), a local repulsive force, can propel the group forward. Here we show that the cell-cell interaction molecule, N-cadherin, regulates both adhesion and repulsion processes during rat Schwann cell (SC) collective migration, which is required for peripheral nerve regeneration. However, distinct from its role in cell-cell adhesion, the repulsion process is independent of N-cadherin trans-homodimerisation and the associated adherens junction complex. Rather, the extracellular domain of N-cadherin is required to present the repulsive Slit2/Slit3 signal at the cell-surface. Inhibiting Slit2/Slit3 signalling inhibits CIL and subsequently collective Schwann cell migration, resulting in adherent, nonmigratory cell clusters. Moreover, analysis of ex vivo explants from mice following sciatic nerve injury showed that inhibition of Slit2 decreased Schwann cell collective migration and increased clustering of Schwann cells within the nerve bridge. These findings provide insight into how opposing signals can mediate collective cell migration and how CIL pathways are promising targets for inhibiting pathological cell migration.

Development of a Semifascicle Graft Technique to Bridge Peripheral Nerve Defect: A Case Report and Animal Study.

Autologous nerve grafting, the criterion standard for bridging peripheral nerves, can cause complications at the donor site. We investigated a novel approach to reconstruct the nerve gap with a split cross-sectional unmatched semifascicle autograft, which was harvested from the distal part of the injured nerve. A patient diagnosed with left-sided frontal branch facial nerve dissection underwent nerve bridging emergency surgery using a semifascicle nerve graft. A sciatic nerve model was used to validate the feasibility and mechanism of this method. Male Sprague-Dawley rats (n = 36) were randomized into (A) intact fascicle, (B) semifascicle, and (C) semifascicle + conduit groups and further subdivided into 4- and 8-week groups for histological analysis of the neurotissue area, fibers, and Schwann cells. The 8-week groups underwent weekly pain and temperature tests; the wet weight of the gastrocnemius muscle was measured after euthanasia. The frontalis of the patient's injured side exhibited movement at 2 months postsurgery and recovered a symmetrical appearance at 13 months. Group A exhibited more neurotissue areas and fibers than groups B and C at week 4; group B had more neurotissue than group C. Group A had greater neurotissue areas than groups B and C at week 8; groups B and C exhibited no differences. The groups displayed no differences regarding nerve fiber, pain, and temperature analysis at week 8. Muscle wet weight of groups A and B exhibited no differences and was higher than that of group C. We demonstrated the clinical translational value of semifascicle nerve grafts; the injured site was both the donor and recipient, thereby avoiding donor site damage and associated complications.

Gut microbiota and their metabolite profiles following peripheral nerve xenotransplantation

BackgroundIntestinal pathogens are associated with xenotransplantation tolerance and rejection. However, changes in the gut microbiota in patients who have undergone peripheral nerve xenotransplantation and their association with immune rejection have not yet been reported. ObjectiveWe aimed to explore intestinal microbes and their metabolites at different time points after peripheral nerve transplantation to provide new insight into improving transplant tolerance. MethodsA peripheral nerve xenotransplantation model was constructed by suturing the segmented nerves of Sprague Dawley rats to those of C57 male mice using xenotransplantation nerve bridging. Fecal samples and intestinal contents were collected at three time points: before surgery (Pre group; n = 10), 1 month after transplantation (Pos1 m group; n = 10), and 3 months after transplantation (Pos3 m group; n = 10) for 16S DNA sequencing and nontargeted metabolome detection. ResultsAlpha diversity results suggested that species diversity was significantly downregulated after peripheral nerve xenotransplantation. There were six gut flora genera with significantly different expression levels after xenotransplantation: four were downregulated and two were upregulated. A comparison of the Pre vs. Pos1 m groups and the Pos1 m vs. Pos3 m groups revealed that the most significant differentially expressed Kyoto Encyclopedia of Genes and Genomes metabolite pathways were involved in phenylalanine, tyrosine, and tryptophan biosynthesis, as well as histidine metabolism. Metabolites with a strong relationship to the differentially expressed microbial flora were identified. ConclusionOur study found lower gut microbiome diversity, with increased short-chain fatty acid (SCFA)-producing and sulfate-reducing bacteria at 1 month post peripheral nerve xenotransplantation, and these were decreased at 3 months post-transplantation. The identification of specific bacterial metabolites is essential for recognizing potential diagnostic markers of xenotransplantation rejection or characterizing therapeutic targets to prevent post-transplant infection.

Clinical evaluation of the perception of post-trauma paresthesia in the mandible, using a biomimetic material: A preliminary study in humans

There is a great effort from numerous research groups in the development of materials and therapeutic strategies for the functional recovery of patients who have suffered peripheral nerve injuries (PNI). In an article in vivo, the formation of a nerve bridge was observed, reconnecting the distal and proximal stumps, in the sciatic nerve of rats, indicating the effective participation of the biomaterial in the recovery of peripheral nerve injuries. For the current pilot study, 15 cases of multiple fractures of the mandible, with involvement of the inferior alveolar nerve (IAN) were selected and studied: JC (control cases) n = 6 with conventional treatment, and JT (treated cases) n = 9, with the use of biomimetic biomaterial. The evaluation of the return to sensitivity was measured through a self-assessment, where the patients assigned scores from 0 to 10, where zero (0) represented the complete absence of sensitivity and ten (10) the normality of the perception of local sensitivity. Patients were evaluated from the preoperative period to the 360th day. The statistical results obtained by the t-Student, Shapiro-Wilk normality and non-parametric One-Way ANOVA tests indicated statistically significant differences (p < 0.005; 0.005 e 0.5 respectively), between the two treatments, which were reflected in the clinical results observed, we also calculate the size of the effect represented by ϵ2, calculated by Cohen's d. The results indicate a great difference between the treatments performed,ϵ2 = 1.00. In the 6 cases followed up in the JC group, four remained with a significant deficit until the end of the evaluations and two indicated the remission of the lack of sensitivity in this period. In the JT group, in 28 days, all cases indicated complete remission of the lack of sensitivity with healing concentration. In one of the cases where there was a complete rupture of the mental nerve, the (score-10) was observed in 60 days. The observed results indicate the existence of a statistical significance between the groups and an important relationship when using the biomimetic biomaterial during the recovery of the perception of sensitivity in polytraumatized patients, compatible with the results observed in laboratory animals, which may indicate its clinical feasibility in the reduction of sequelae in PNI.

Metal organic framework-modified bioadaptable implant potentiates the reconstruction of nerve microenvironment via immunometabolism reprogramming

Whereas immune homeostasis and metabolic reprogramming are recognized as fundamental players in the restoration of posttraumatic nerve microenvironment, much less is known about the role of immunometabolism in this progress. In nerve tissue, the immune identity of resident macrophages contributes to the reshaping of metabolic states. In turn, rapid metabolic shifts and on-demand energy production are also needed to support versatile macrophage functions. Here, we develop a self-powered nerve bridging scaffold by integrating metal organic frameworks (MOFs) and reduced graphene oxide (rGO) nanoparticles into polycaprolactone (PCL) substrates. This provides a bioadaptable neural interface to enable the improved oxidative metabolism in injured nerves and phenotypic switch of infiltrated macrophages. The unique molecular identity of reprogrammed macrophages is also identified, with macrophages displaying enhanced oxidative phosphorylation, mitochondrial bioenergetics and suppressed calcium signaling. Thus, our piezoelectric scaffolds have matched bioadaptability with nerve immunometabolism and facilitate nerve repair.

Time course of functional recovery after 1 cm sciatic nerve resection in rats with or without surgical intervention - measured by grip strength and locomotor activity

The rat sciatic nerve (SN) is the most frequently used model in experimental research on peripheral nerve injuries. Within the broad range of evaluation methods to determine the experimental outcome, recovery of behavior represents the major criterion to assess functional regeneration. The grasping test indicates when recovery begins and its improvement with time. However, lesions of the SN have yet remained unstudied with this method. Therefore, rats received a SN resection and were divided into experimental groups: 1) control with lesion only, 2) nerve bridge, and 3) autograft. During weekly sessions, the grasping test measured the grip strength, and the locomotor behavior was assessed in the open field. Finally, the nerves were prepared for electrophysiology and histomorphometry. Autograft recovered grasping after 7 weeks with the strongest improvement afterwards. Nerve tube allowed grasping by week 12. Control animals did not recover. In the open field, no differences were observed between the groups. Recordings were possible only in the autograft group, which could be explained by higher number of regenerated fibers. This study indicates that grasping data correspond with physiological and anatomical findings. We conclude that the grasping test is a valid method to evaluate functional recovery after SN resection in rats.

Peripheral nerve defects repaired with autogenous vein grafts filled with platelet-rich plasma and active nerve microtissues and evaluated by novel multimodal ultrasound techniques

BackgroundDeveloping biocompatible nerve conduits that accelerate peripheral nerve regeneration, lengthening and functional recovery remains a challenge. The combined application of nerve microtissues and platelet-rich plasma (PRP) provides abundant Schwann cells (SCs) and various natural growth factors and can compensate for the deficiency of SCs in the nerve bridge, as well as the limitations of applying a single type of growth factor. Multimodal ultrasound evaluation can provide additional information on the stiffness and microvascular flow perfusion of the tissue. This study was designed to investigate the effectiveness of a novel tissue-engineered nerve graft composed of an autogenous vein, nerve microtissues and PRP in reconstructing a 12-mm tibial nerve defect and to explore the value of multimodal ultrasound techniques in evaluating the prognosis of nerve repair.MethodsIn vitro, nerve microtissue activity was first investigated, and the effects on SC proliferation, migration, factor secretion, and axonal regeneration of dorsal root ganglia (DRG) were evaluated by coculture with nerve microtissues and PRP. In vivo, seventy-five rabbits were equally and randomly divided into Hollow, PRP, Micro-T (Microtissues), Micro-T + PRP and Autograft groups. By analysing the neurological function, electrophysiological recovery, and the comparative results of multimodal ultrasound and histological evaluation, we investigated the effect of these new nerve grafts in repairing tibial nerve defects.ResultsOur results showed that the combined application of nerve microtissues and PRP could significantly promote the proliferation, secretion and migration of SCs and the regeneration of axons in the early stage. The Micro-T + PRP group and Autograft groups exhibited the best nerve repair 12 weeks postoperatively. In addition, the changes in target tissue stiffness and microvascular perfusion on multimodal ultrasound (shear wave elastography; contrast-enhanced ultrasonography; Angio PlaneWave UltrasenSitive, AngioPLUS) were significantly correlated with the histological results, such as collagen area percentage and VEGF expression, respectively.ConclusionOur novel tissue-engineered nerve graft shows excellent efficacy in repairing 12-mm defects of the tibial nerve in rabbits. Moreover, multimodal ultrasound may provide a clinical reference for prognosis by quantitatively evaluating the stiffness and microvescular flow of nerve grafts and targeted muscles.

Piezoelectric stimulation from electrospun composite nanofibers for rapid peripheral nerve regeneration

Peripheral nerve injuries vary among patients. Cell-based or acellular nerve conduits have a high peripheral nerve regeneration potential. However, they are not ideal for complicated nerve differentiations and are prone to unclear effects of cytokine interactions. Delayed nerve axon regeneration could be ascribed to a lack of regulation of the regenerative microenvironment. Electrical stimulation influences nerve regeneration by regulating sensitive targets. Here, a piezoelectric nerve conduit was developed using a composite of PCL/ZnO nanofiber (PZNF) via electrospinning. Endogenous piezoelectric stimulation from PZNF facilitated sciatic nerve regeneration. This material inherits polycaprolactone characteristics and is a biocompatible material. It generated stable and desired endogenous electrical stimulations. PZNF demonstrated faster and superior sciatic nerve repair in vivo than polycaprolactone nanofiber and nerve bridging in situ. Piezoelectric stimulation of PZNF could substantially increase nerve growth factor/vascular endothelial growth factor expression. Furthermore, the PZNF considerably promoted rapid nerve repair and shortened function recovery (within 4 weeks) in vivo. Moreover, an increase in growth factor receptor-bound protein-2 (GRB2) expression activated downstrem pathway: RAS/MAPK pathway after piezoelectricity stimulation, indicating that GRB2 may be an electrically sensitive protein and a hint protein of electrical stimulation-induced regeneration. This study offers a novel strategy of applying piezoelectric stimulation in rapid peripheral nerve regeneration.

Blood Vessels: The Pathway Used by Schwann Cells to Colonize Nerve Conduits.

The repair of severe nerve injuries requires an autograft or conduit to bridge the gap and avoid axon dispersion. Several conduits are used routinely, but their effectiveness is comparable to that of an autograft only for short gaps. Understanding nerve regeneration within short conduits could help improve their efficacy for longer gaps. Since Schwann cells are known to migrate on endothelial cells to colonize the “nerve bridge”, the new tissue spontaneously forming to connect the injured nerve stumps, here we aimed to investigate whether this migratory mechanism drives Schwann cells to also proceed within the nerve conduits used to repair large nerve gaps. Injured median nerves of adult female rats were repaired with 10 mm chitosan conduits and the regenerated nerves within conduits were analyzed at different time points using confocal imaging of sequential thick sections. Our data showed that the endothelial cells formed a dense capillary network used by Schwann cells to migrate from the two nerve stumps into the conduit. We concluded that angiogenesis played a key role in the nerve conduits, not only by supporting cell survival but also by providing a pathway for the migration of newly formed Schwann cells.

Macrophages facilitate peripheral nerve regeneration by organizing regeneration tracks through Plexin-B2.

The regeneration of peripheral nerves is guided by regeneration tracks formed through an interplay of many cell types, but the underlying signaling pathways remain unclear. Here, we demonstrate that macrophages are mobilized ahead of Schwann cells in the nerve bridge after transection injury to participate in building regeneration tracks. This requires the function of guidance receptor Plexin-B2, which is robustly up-regulated in infiltrating macrophages in injured nerves. Conditional deletion of Plexin-B2 in myeloid lineage resulted in not only macrophage misalignment but also matrix disarray and Schwann cell disorganization, leading to misguided axons and delayed functional recovery. Plexin-B2 is not required for macrophage recruitment or activation but enables macrophages to steer clear of colliding axons, in particular the growth cones at the tip of regenerating axons, leading to parallel alignment postcollision. Together, our studies unveil a novel reparative function of macrophages and the importance of Plexin-B2-mediated collision-dependent contact avoidance between macrophages and regenerating axons in forming regeneration tracks during peripheral nerve regeneration.

Up-Regulation of CD146 in Schwann Cells Following Peripheral Nerve Injury Modulates Schwann Cell Function in Regeneration.

CD146 is cell adhesion molecule and is implicated in a variety of physiological and pathological processes. However, the involvement of CD146 in peripheral nerve regeneration has not been studied yet. Here, we examine the spatial and temporal expression pattern of CD146 in injured mouse sciatic nerve via high-throughput data analysis, RT-PCR and immunostaining. By microarray data analysis and RT-PCR validation, we show that CD146 mRNA is significantly up-regulated in the nerve bridge and in the distal nerve stump following mouse sciatic nerve transection injury. By single cell sequencing data analysis and immunostaining, we demonstrate that CD146 is up-regulated in Schwann cells and cells associated with blood vessels following mouse peripheral nerve injury. Bioinformatic analysis revealed that CD146 not only has a key role in promoting of blood vessel regeneration but also regulates cell migration. The biological function of CD146 in Schwann cells was further investigated by knockdown of CD146 in rat primary Schwann cells. Functional assessments showed that knockdown of CD146 decreases viability and proliferation of Schwann cells but increases Schwann cell migration. Collectively, our findings imply that CD146 could be a key cell adhesion molecule that is up-regulated in injured peripheral nerves to regulate peripheral nerve regeneration.

Bridge technique for hemifacial spasm with vertebral artery involvement

BackgroundTo assess efficacy and safety of a newly developed decompression technique in microvascular decompression for hemifacial spasm (HFS) with vertebral artery (VA) involvement.MethodsA rigid Teflon (Bard® PTFE Felt Pledget, USA) with the ends placed between the lower pons and the flocculus creates a free space over the root exit zone (REZ) of the facial nerve (bridge technique). The bridge technique and the conventional sling technique for VA-related neurovascular compression were compared retrospectively in 60 patients. Elapsed time for decompression, number of Teflon pieces used during the procedure, and incidences of intraoperative manipulation to the lower cranial nerves were investigated. Postoperative outcomes and complications were retrospectively compared in both techniques.ResultsThe time from recognition of the REZ to completion of the decompression maneuvers was significantly shorter, and fewer Teflon pieces were required in the bridge technique than in the sling technique. Lower cranial nerve manipulations were performed less in the bridge technique. Although statistical analyses revealed no significant differences in surgical outcomes except spasm-free at postoperative 1 month, the bridge technique is confirmed to provide spasm-free outcomes in the long-term without notable complications.ConclusionsThe bridge technique is a safe and effective decompression method for VA-involved HFS.

GDNF to the rescue: GDNF delivery effects on motor neurons and nerves, and muscle re-innervation after peripheral nerve injuries.

Peripheral nerve injuries commonly occur due to trauma, like a traffic accident. Peripheral nerves get severed, causing motor neuron death and potential muscle atrophy. The current golden standard to treat peripheral nerve lesions, especially lesions with large (≥ 3 cm) nerve gaps, is the use of a nerve autograft or reimplantation in cases where nerve root avulsions occur. If not tended early, degeneration of motor neurons and loss of axon regeneration can occur, leading to loss of function. Although surgical procedures exist, patients often do not fully recover, and quality of life deteriorates. Peripheral nerves have limited regeneration, and it is usually mediated by Schwann cells and neurotrophic factors, like glial cell line-derived neurotrophic factor, as seen in Wallerian degeneration. Glial cell line-derived neurotrophic factor is a neurotrophic factor known to promote motor neuron survival and neurite outgrowth. Glial cell line-derived neurotrophic factor is upregulated in different forms of nerve injuries like axotomy, sciatic nerve crush, and compression, thus creating great interest to explore this protein as a potential treatment for peripheral nerve injuries. Exogenous glial cell line-derived neurotrophic factor has shown positive effects in regeneration and functional recovery when applied in experimental models of peripheral nerve injuries. In this review, we discuss the mechanism of repair provided by Schwann cells and upregulation of glial cell line-derived neurotrophic factor, the latest findings on the effects of glial cell line-derived neurotrophic factor in different types of peripheral nerve injuries, delivery systems, and complementary treatments (electrical muscle stimulation and exercise). Understanding and overcoming the challenges of proper timing and glial cell line-derived neurotrophic factor delivery is paramount to creating novel treatments to tend to peripheral nerve injuries to improve patients’ quality of life.

Application of Extradural Nerve Root Transfer in the Restoration of Lower Limb Function in Spinal Cord Injury: Hypothesis and a Cadaver Feasibility Study.

Two fresh-frozen and six formalin-fixed cadavers were included in the study. To ascertain whether transferring T9 or T11 ventral root (VR) to L2 VR and T10 or T12 VR to L3 VR in restoring lower limb function after spinal cord injury is anatomically feasible. Lower limb paralysis impairs the quality of the life and places burden on the whole society. However, no significant improvement in this area was achieved during recent years. In the present study, two fresh-frozen and six formalin-fixed cadavers were dissected to confirm the anatomical feasibility. A limited laminectomy was performed to expose the T9-L3 extradural nerve roots. T9 and T10 VR were anastomosed to L2 and L3 VR respectively, or T11 and T12 VR were anastomosed to L2 and L3 VR respectively. The pertinent distances between the donor and recipient nerves were measured and H&E staining was used to detect the axon number and cross-section area of each VR. The limited incision was performed to expose the T9-L3 nerve root. According to the anatomic landmark of dorsal root ganglion, each VR could be isolated from each extradural nerve root. The T9 or T11 VR needs sural nerve graft to be transferred to L2 VR, and T10 or T12 VR also needs a nerve bridge to connect to L3 VR. The nerve numbers of T9, T10, T11, T12, L2, and L3 VRs and the sural nerves were measured respectively. The cross-section areas of T9, T10, T11, T12, L2, and L3 VRs and sural nerves were measured respectively. Our study suggested that application of transferring T9 or T11 VR to L2 VR and T10 or T12 VR to L3 VR in restoring lower limb function is anatomically feasible.Level of Evidence: 5.

Materials for peripheral nerve repair constructs: Natural proteins or synthetic polymers?

The efficacious repair of severe peripheral nerve injuries is currently an unmet clinical need, and biomaterial constructs offer a promising approach to help promote nerve regeneration. Current research focuses on the development of more sophisticated constructs with complex architecture and the addition of regenerative agents to encourage timely reinnervation and promote functional recovery. This review surveyed the present landscape of nerve repair construct literature with a focus on six selected materials that are frequently encountered in this application: the natural proteins collagen, chitosan, and silk, and the synthetic polymers poly-ε-caprolactone (PCL), poly-lactic-co-glycolic acid (PLGA) and poly-glycolic acid (PGA). This review also investigated the use of cell therapy in nerve repair constructs, and in all instances concentrated on publications reporting constructs developed and tested in vivo in the last five years (2015–2020). Across the selected literature, the popularity of natural proteins and synthetic polymers appears to be broadly equivalent, with a similar number of studies reporting successful outcomes in vivo. Both material types are also utilised as vehicles for cell therapy, which has much potential to improve the results of nerve bridging for treating longer gaps.

Migrating Schwann cells direct axon regeneration within the peripheral nerve bridge.

Schwann cells within the peripheral nervous system possess a remarkable regenerative potential. Current research shows that peripheral nerve-associated Schwann cells possess the capacity to promote repair of multiple tissues including peripheral nerve gap bridging, skin wound healing, digit tip repair as well as tooth regeneration. One of the key features of the specialized repair Schwann cells is that they become highly motile. They not only migrate into the area of damaged tissue and become a key component of regenerating tissue but also secrete signaling molecules to attract macrophages, support neuronal survival, promote axonal regrowth, activate local mesenchymal stem cells, and interact with other cell types. Currently, the importance of migratory Schwann cells in tissue regeneration is most evident in the case of a peripheral nerve transection injury. Following nerve transection, Schwann cells from both proximal and distal nerve stumps migrate into the nerve bridge and form Schwann cell cords to guide axon regeneration. The formation of Schwann cell cords in the nerve bridge is key to successful peripheral nerve repair following transection injury. In this review, we first examine nerve bridge formation and the behavior of Schwann cell migration in the nerve bridge, and then discuss how migrating Schwann cells direct regenerating axons into the distal nerve. We also review the current understanding of signals that could activate Schwann cell migration and signals that Schwann cells utilize to direct axon regeneration. Understanding the molecular mechanism of Schwann cell migration could potentially offer new therapeutic strategies for peripheral nerve repair.

Transfert du nerf obturateur vers le nerf tibial au moyen d’une greffe de nerf saphène pour le traitement des avulsions du plexus sacré : étude cadavérique

IntroductionIn cases of sacral nerve avulsion injuries, proximal nerve stumps are not available because of its protected position in pelvis, and results of nerve repair or graft are unsatisfactory. Nerve transfer can reduce the regeneration time and improve the results of recovery. HypothesisThe obturator nerve transfer to the tibial nerve via saphenous nerve graft is possible and feasible. Materials and methodsTen male adult cadaveric lower limbs dissected to identify the location of the anterior branch of obturator nerve, the saphenous nerve and the medial gastrocnemius branch. The saphenous nerve was cut from its origin and transferred to the anterior branch of obturator nerve. As well, it was cut distally and transferred to the medial gastrocnemius branch. After nerve coaptation, surface area and fascicle count were determined by histological methods. ResultsIn all limbs, the proximal and distal stumps of saphenous nerve were reached the anterior branch of obturator and the medial gastrocnemius branch, respectively without tension. The mean of fascicle number in the anterior branch of obturator nerve, proximal and distal stump of the saphenous nerve and stump of medial gastrocnemius nerve branch were 2.90±0.99, 4.50±2.70, 4.00±2.26 and 4.30±1.25, respectively. DiscussionThis study showed that it is possible to transfer the obturator nerve to the medial gastrocnemius branch via saphenous nerve bridge; and their histological parameters are match in a good manner. Therefore, this technique is suggested for patients with sacral nerve avulsion injuries. Level of evidenceIV, case series of cadaveric study.

Obturator to tibial nerve transfer via saphenous nerve graft for treatment of sacral plexus root avulsions: A cadaveric study

IntroductionIn cases of sacral nerve avulsion injuries, proximal nerve stumps are not available because of its protected position in pelvis, and results of nerve repair or graft are unsatisfactory. Nerve transfer can reduce the regeneration time and improve the results of recovery. HypothesisThe obturator nerve transfer to the tibial nerve via saphenous nerve graft is possible and feasible. Materials and methodsTen male adult cadaveric lower limbs dissected to identify the location of the anterior branch of obturator nerve, the saphenous nerve and the medial gastrocnemius branch. The saphenous nerve was cut from its origin and transferred to the anterior branch of obturator nerve. As well, it was cut distally and transferred to the medial gastrocnemius branch. After nerve coaptation, surface area and fascicle count were determined by histological methods. ResultsIn all limbs, the proximal and distal stumps of saphenous nerve were reached the anterior branch of obturator and the medial gastrocnemius branch, respectively without tension. The mean of fascicle number in the anterior branch of obturator nerve, proximal and distal stump of the saphenous nerve and stump of medial gastrocnemius nerve branch were 2.90±0.99, 4.50±2.70, 4.00±2.26 and 4.30±1.25, respectively. DiscussionThis study showed that it is possible to transfer the obturator nerve to the medial gastrocnemius branch via saphenous nerve bridge; and their histological parameters are match in a good manner. Therefore, this technique is suggested for patients with sacral nerve avulsion injuries. Level of evidenceIV, case series of cadaveric study.