Peripheral Nerve Reconstruction Research Articles

The Role of Macrophages in Nerve Regeneration: Polarization and Combination with Tissue Engineering.

Peripheral nerve regeneration after trauma poses a substantial clinical challenge that has already been investigated for many years. Infiltration of immune cells is a critical step in the response to nerve damage that creates a supportive microenvironment for regeneration. In this work, we focus on a special type of immune cell, macrophage, in addressing the problem of neuronal regeneration. We discuss the complex endogenous mechanisms of peripheral nerve injury and regrowth vis-à-vis macrophages, including their recruitment, polarization, and interplay with Schwann cells post-trauma. Furthermore, we elucidate the underlying mechanisms by which exogenous stimuli govern the above events. Finally, we summarize the necessary roles of macrophages in peripheral nerve lesions and reconstruction. There are many challenges in controlling macrophage functions to achieve complete neuronal regeneration, even though considerable progress has been made in understanding the connection between these cells and peripheral nerve damage.

3D-bioprinted RGD-Alg/GelMA/PCL scaffolds laden with Schwann-like cells for peripheral nerve reconstruction

3D-bioprinted RGD-Alg/GelMA/PCL scaffolds laden with Schwann-like cells for peripheral nerve reconstruction

Constructing Nerve Guidance Conduit using dECM‐Doped Conductive Hydrogel to Promote Peripheral Nerve Regeneration

AbstractPeripheral nerve injury often leads to the loss of neurological functions due to the slow regeneration rate and inefficient functional reconstruction. Current clinical treatments using nerve guidance conduits (NGCs) still face challenges in providing a biomimetic microenvironment to promote nerve repair. Herein, decellularized extracellular matrix (dECM) is obtained from porcine Achilles tendon and crosslinked with 3‐amino‐4‐methoxybenzoic acid grafted gelatin (PAMB‐G) to obtain conductive hydrogels. Then, a novel nerve guidance conduit is developed by assembling poly(vinyl alcohol) (PVA) conduit and conductive ECM@PAMB‐G hydrogel. This bioengineered ECM@PAMB‐G/PVA conduit demonstrated excellent cytocompatibility, electrical conductivity, mechanical properties, and biodegradability. In vitro experiments confirmed that the ECM@PAMB‐G hydrogel significantly promotes the proliferation and migration of PC12 cells and primary Schwann cells, as well as the growth of dorsal root ganglion (DRG) axons. Furthermore, in vivo studies in a rat sciatic nerve model exhibited improvements in axonal regeneration, Schwann cell migration, myelin sheath formation, and functional recovery mediated by the ECM@PAMB‐G/PVA conduit. This work demonstrates the synergistic effects of extracellular matrix and electrical cues in enhancing peripheral nerve regeneration. The ECM@PAMB‐G/PVA nerve guidance conduit shows potential as an alternative to autografts for supporting peripheral nerve reconstruction.

Fas ligand regulate nerve injury and repair by affecting AKT, β-catenin, and NF-κB pathways

ObjectiveTo investigate the regulatory effect of Fas-L on the repair and regeneration of peripheral extension injury in rats. MethodsThis study aimed to explore the effects of Fas-L on apoptosis and axonal regeneration of dorsal root ganglion (DRG) cells in rat peripheral nerve repair and regeneration by using several relevant experimental techniques from the injured nerve animal model, cell biology, and molecular biology. ResultsThe expression level of Fas-L in DRG tissues was significantly down-regulated after sciatic nerve injury. Interference with Fas-L can significantly promote the regeneration of DRG neuronal axons and inhibit apoptosis, while the overexpression of Fas-L is contrary to it. Moreover, Fas-L may play a role in the regulation of DRG function and the repair and regeneration of peripheral nerves in Sprague Dawley (SD) rats by affecting several signaling pathways, such as p-AKT/AKT, β-catenin, and NF-κB. ConclusionFas-L may have a certain effect on the repair and regeneration of peripheral nerve injury in SD rats, which may provide an experimental basis and a new theoretical basis for the functional reconstruction of peripheral nerves. Significance statementThe expression level of Fas-L in DRG tissues was significantly down-regulated after sciatic nerve injury. Fas-L can significantly promote the regeneration of DRG neuronal axons and inhibit apoptosis. Fas-L may play a role in the regulation of DRG function and the repair and regeneration of peripheral nerves in SD rats by affecting several signaling pathways, such as p-AKT/AKT, β-catenin, and NF-κB. Fas-L may have a certain effect on the repair and regeneration of peripheral nerve injury in SD rats, which may provide an experimental basis and a new theoretical basis for the functional reconstruction of peripheral nerves.

Peripheral nerve regeneration following scaffold-free conduit transplant of autologous dermal fibroblasts: a non-randomised safety and feasibility trial

BackgroundThe use of Bio 3D nerve conduits is a promising approach for peripheral nerve reconstruction. This study aimed to assess their safety in three patients with peripheral nerve defects in their hands.MethodsWe describe a single institution, non-blinded, non-randomised control trial conducted at Kyoto University Hospital. Eligibility criteria included severed peripheral nerve injuries or a defect in the region distal to the wrist joint not caused by a congenital anomaly; a defect with a length of ≤20 mm in a nerve with a diameter ≤2 mm; failed results of sensory functional tests; ability to register in the protocol within 6 months from the day of injury; refusal of artificial nerve or autologous nerve transplantation; age 20–60 years; and willingness to participate and provide informed written consent. Six weeks before transplantation, skin was harvested, dermal fibroblasts were isolated and expanded, and Bio 3D nerve conduits were created using a Bio 3D printer. Bio 3D nerve conduits were transplanted into the patients’ nerve defects. The safety of Bio 3D nerve conduits in patients with a peripheral nerve injury in the distal part of the wrist joint were assessed over a 48-week period after transplantation.ResultsNo adverse events related to the use of Bio 3D nerve conduits were observed in any patient, and all three patients completed the trial.ConclusionsBio 3D nerve conduits were successfully used for clinical nerve reconstruction without adverse events and are a possible treatment option for peripheral nerve injuries.

Reconstruction of Upper Extremity Peripheral Nerve Injuries Using an Epineurial-Like Collagen Device—A Prospective Clinical Study

Abstract Background Epineurium acts as a barrier to protect nerves from injury and maintains its structural and functional integrity. A device was developed to mimic the native structure of epineurium. The aim of this study was to evaluate its biological characteristics and clinical performance in the reconstruction of upper extremity peripheral nerves. Methods Scanning electron microscopy, transmission electron microscopy, and enhanced microcomputed tomography were used to examine the ultrastructural characteristics of the device. A prospective case series with 2-year follow-up was undertaken and reported. Patients who required nerve reconstruction in the upper extremities were included and underwent single or multiple nerve reconstructions in one or both upper limbs. Results The device mimics the structural and biological properties of epineurium. During surgical use, it can form compression-free and self-engaged wrapping around the repaired nerves. A total of 36 peripheral nerve reconstructions were performed using either nerve transfer or nerve grafting in 19 patients. Of these, 14 patients had upper limb nerve injuries and 5 had C5 to C8 spinal cord injuries resulting in tetraplegia. Nerve reconstruction using the device restored peripheral nerve function, with functional motor recovery (FMR) observed in 76% of the most proximal target muscle at 12 months and 85% of most proximal muscles at 24 months post-treatment. FMR was observed in 61% of all target muscles at 12 months and 75% at 24 months post-treatment. Conclusion The device restored FMR in the upper extremities in patients with peripheral nerve or spinal cord injuries. Level of Evidence Therapeutic IV

Comparative Analysis of Various Spider Silks in Regard to Nerve Regeneration: Material Properties and Schwann Cell Response.

Peripheral nerve reconstruction through the employment of nerve guidance conduits with Trichonephila dragline silk as a luminal filling has emerged as an outstanding preclinical alternative to avoid nerve autografts. Yet, it remains unknown whether the outcome is similar for silk fibers harvested from other spider species. This study compares the regenerative potential of dragline silk from two orb-weaving spiders, Trichonephila inaurata and Nuctenea umbratica, as well as the silk of the jumping spider Phidippus regius. Proliferation, migration, and transcriptomic state of Schwann cells seeded on these silks are investigated. In addition, fiber morphology, primary protein structure, and mechanical properties are studied. The results demonstrate that the increased velocity of Schwann cells on Phidippus regius fibers can be primarily attributed to the interplay between the silk's primary protein structure and its mechanical properties. Furthermore, the capacity of silk fibers to trigger cells toward a gene expression profile of a myelinating Schwann cell phenotype is shown. The findings for the first time allow an in-depth comparison of the specific cellular response to various native spider silks and a correlation with the fibers' material properties. This knowledge is essential to open up possibilities for targeted manufacturing of synthetic nervous tissue replacement.

Combination of stem cells and nerve guide conduit for the treatment of peripheral nerve injury: A meta-analysis.

Many small-sized, single-center preclinical studies have investigated the benefits of introducing stem cells into the interior of nerve conduit. The aims of this meta-analysis are to review and contrast the effects of various types of stem cells in in vivo models used to reconstruct peripheral nerve injuries (PNIs) and to assess the reliability and stability of the available evidence. A systematic search was conducted using Cochrane Library, Embase, PubMed, and Web of Science to identify studies conducted from January 1, 2000, to September 21, 2022, and investigate stem cell therapy in peripheral nerve reconstruction animal models. Studies that met the relevant criteria were deemed eligible for this meta-analysis. Fifty-five preclinical studies with a total of 1234 animals were incorporated. Stem cells demonstrated a positive impact on peripheral nerve regeneration at different follow-up times in the forest plots of five outcome indicators: compound muscle action potential (CMAP) amplitude, latency, muscle mass ratio, nerve conduction velocity, and sciatic functional index (SFI). In most comparisons, stem cell groups showed substantial differences compared with the control groups. The superior performance of adipose-derived stem cells (ADSCs) in terms of SFI, CMAP amplitude, and latency (p < .001) was identified. The findings consistently demonstrated a favorable outcome in the reconstruction process when utilizing different groups of stem cells, as opposed to control groups where stem cells were not employed.

Reconsidering the Standard of Care for Peripheral Nerve Reconstruction.

Reconsidering the Standard of Care for Peripheral Nerve Reconstruction.

Fascicular shifting in the reconstruction of brachial plexus injuries: an anatomical and clinical evaluation.

Until recently, autologous sensory nerve grafting has remained the gold-standard technique in peripheral nerve reconstruction. However, there are several disadvantages to these grafts, such as donor site morbidity, limited availability, and a qualitative mismatch. Building on this shortage, a new concept, the fascicular shift procedure, was proposed and successfully demonstrated nerve regeneration in a rat nerve injury model. This approach involves harvesting a fascicular group distal to a peripheral nerve injury and shifting it to bridge the defect. The present study aimed to evaluate the clinical applicability of this technique in brachial plexus reconstruction. The supra- and infraclavicular nerves of the brachial plexus were bilaterally explored in 18 formalin-fixed cadaveric specimens. Following dissection, their fascicular shifting potential was evaluated. The medial antebrachial cutaneous and sural nerves were investigated and used as references for the required cross-sectional area of potential nerve grafts. Furthermore, 29 brachial plexus injuries, which qualified for surgical repair, were subjected to retrospective analysis. The intraoperatively measured lengths of the harvested and ultimately transplanted nerve grafts served as a basis to assess graft requirements in brachial plexus lesions. The transplanted nerve grafts measured a total length of 51.9 ± 28.1 cm in brachial plexus injuries. The individual inserted nerve grafts averaged 10.3 ± 5.1 cm. In the anatomical exploration, the ulnar and median nerves qualified for fascicular shifting. Their fascicular graft lengths measured 26.6 ± 2.5 cm and 24.8 ± 5.2 cm, respectively. The long thoracic, suprascapular, musculocutaneous, thoracodorsal, and axillary nerves were not suitable for fascicular shifting. The sensory graft length of the medial antebrachial cutaneous nerve measured 20.6 ± 3.4 cm. In the surgical reconstruction of brachial plexus injuries, fascicular shifting of the ulnar and median nerves provides sufficient donor material. Even though potential donor length is limited in the radial nerve, it may still help to expand the surgical armamentarium in selected clinical scenarios. Overall, the fascicular shift procedure presents a novel alternative to allow modality-matched grafting in the reconstruction of large proximal nerve defects and was found to be an attractive option in brachial plexus reconstruction.

Histologic Comparison of the Fascicular Area of Processed Nerve Allograft Versus Cabled Sural Nerve Autograft.

The use of multiple cables of sural nerve autograft is common for peripheral nerve reconstruction when injured nerve caliber exceeds the nerve graft caliber. Although the optimal matching of neural to nonneural elements and its association with functional outcomes are unknown, it is reasonable to consider maximizing the neural tissue structure available for nerve regeneration. No prior studies have compared directly the cross-sectional fascicular area between cabled nerve autografts and size-selected nerve allografts. This study evaluated the cross-sectional fascicular area between native nerve stumps and two reconstructive nerve grafting methods: cabled sural nerve autograft (CSNA) and processed nerve allograft (PNA). CSNA from matched cadaveric specimens and PNA were used to reconstruct nerve defects in the median and ulnar nerves of six pairs of cadaveric specimens. Nerve reconstructions were done by fellowship-trained hand surgeons. The total nerve area, fascicular area, and nonfascicular area were measured histologically. The CSNA grafts had significantly less fascicular area than PNA and caliber-matched native nerve. The PNA grafts had a significantly higher percent fascicular area compared with the intercalary CNSA graft. Fascicular area was significantly greater in PNA versus CSNA. The PNA consistently demonstrated a match in fascicular area closer to the native nerve stumps than CSNA, where CSNA had significantly smaller fascicular area compared with native nerve stumps.

An experimental model of peripheral nerve electrical injury in rats

IntroductionAlthough several studies have investigated models of nerve electrical injury, only a few have focused on electrical injury to peripheral nerves, which is a common and intractable problem in clinical practice. Here, we describe an experimental rat model of peripheral nerve electrical injury and its assessment. MethodsA total of 120 animals were subjected to short-term corrective electrostimulation (50 Hz, 1-s duration) applied at varying voltages (control, 65, 75, 100, 125, and 150 V) to the exposed left sciatic nerve. Behavioural testing, electrophysiological measurements, and histopathological observation of the sciatic nerve were conducted at 1-, 2-, 4-, and 8-w follow-ups. ResultsNo functional defects were noted in the groups that received 65-V stimulation at any time point. Sciatic nerve functional defects were found after 2 w in animals that received 75-V stimulation, but function returned to normal after 4 w. In animals that received 100-V and 125-V stimulation, functional defects were observed at 4 w, but had partially recovered by 8 w. Conversely, animals that received 150-V stimulation did not show recovery after 8 w. ConclusionWe presented a model of peripheral nerve electrical injury that avoided the interference of various external factors, such as current instability, compression of the surrounding tissues, and altered blood supply. The model allowed quantitation and ranking of the nerve injury into four degrees. It facilitated effective evaluation of nerve function impairment and repair after injury. It can be used post-surgically to evaluate peripheral nerve impairment and reconstruction and enables translational interpretation of results, which may improve understanding of the mechanisms underlying the progression of peripheral nerve electrical injury.

Reconstruction of Peripheral Nerves after Neuroma, and Tumor Resection with Processed Allogenic Nerve Graft (AVANCE® Nerve Graft)

Introduction: Autologous nerve grafts are accompanied by morbidity of the donor site, leading to loss of sensation and possible complications such as end neuroma formation or persistent pain. Moreover, the indications are narrow mostly limited to defects in larger motor nerves with good prognosis. One alternative to autografts might be the commercially available allograft (Avance® Nerve Graft). The aim of this study was to assess the safety and outcome of the Avance® Nerve Graft for the reconstruction of peripheral nerves after neuromas, and tumor resection. Materials and Methods: For this purpose, ten patients with eleven implanted grafts were recruited for the prospective study. Five patients suffered from a neuroma-in-continuity, four from an terminal neuroma formation and two from Schwannomas. Seven patients were symptomatic for pain. After the resection, the peripheral nerves were reconstructed with the Avance® Nerve Graft. The patients were followed up for at least six months, by assessing recovery of motor, and sensibility and pain reduction. Results: A significant decrease in pain levels was observed after reconstruction. All patients achieved or remained a meaningful sensory function with levels of S3 or above. Regarding motor function, 85.7% (6 of 7 patients) demonstrated M3 or higher. One patient received a revisional reconstruction upon recurrent neuroma formation. In summary, all patients demonstrated signs of recovery and improvement of their paint situation. Nevertheless, one patient missed a meaningful motor recovery and a second one underwent an additional intervention. Conclusion: The reconstruction with Avance® Nerve Graft demonstrated good outcomes for motor, and sensory function, by achieving a pain reduction in all patients. Of particular interest, was the reconstruction of lesioned purely sensible nerves, for those currently no reasonable reconstruction option exists. Declaration of potential conflicts of interest The financial resources for the conduct of the RANGER study at the Medical University of Vienna are provided by Axogen Inc.

Benefit of Adjuvant Mesenchymal Stem Cell Transplantation to Critical-Sized Peripheral Nerve Defect Repair: A Systematic Review and Meta-Analysis of Preclinical Studies.

Critically sized nerve defects cause devastating life-long disabilities and require interposition for reconstruction. Additional local application of mesenchymal stem cells (MSCs) is considered promising to enhance peripheral nerve regeneration. To better understand the role of MSCs in peripheral nerve reconstruction, we performed a systematic review and meta-analysis of the effects of MSCs on critically sized segment nerve defects in preclinical studies. 5146 articles were screened following PRISMA guidelines using PubMed and Web of Science. A total of 27 preclinical studies (n = 722 rats) were included in the meta-analysis. The mean difference or the standardized mean difference with 95% confidence intervals for motor function, conduction velocity, and histomorphological parameters of nerve regeneration, as well as the degree of muscle atrophy, was compared in rats with critically sized defects and autologous nerve reconstruction treated with or without MSCs. The co-transplantation of MSCs increased the sciatic functional index (3.93, 95% CI 2.62 to 5.24, p < 0.00001) and nerve conduction velocity recovery (1.49, 95% CI 1.13 to 1.84, p = 0.009), decreased the atrophy of targeted muscles (gastrocnemius: 0.63, 95% CI 0.29 to 0.97 p = 0.004; triceps surae: 0.08, 95% CI 0.06 to 0.10 p = 0.71), and promoted the regeneration of injured axons (axon number: 1.10, 95% CI 0.78 to 1.42, p < 0.00001; myelin sheath thickness: 0.15, 95% CI 0.12 to 0.17, p = 0.28). Reconstruction of critically sized peripheral nerve defects is often hindered by impaired postoperative regeneration, especially in defects that require an autologous nerve graft. This meta-analysis indicates that additional application of MSC can enhance postoperative peripheral nerve regeneration in rats. Based on the promising results in vivo experiments, further studies are needed to demonstrate potential clinical benefits.

NPS-Crosslinked Fibrin Gels Load with EMSCs to Repair Peripheral Nerve Injury in Rats.

Neural tissue engineering has been introduced as a novel therapeutic strategy for trauma-induced sciatic nerve defects. Here, a neuropeptide S (NPS)-crosslinked fibrin scaffolds (NPS@Fg) loaded with an ectomesenchymal stem cell (EMSC) system to bridge an 8-mm sciatic nerve defect in rats are reported. The Schwann cell-like and neural differentiation of the EMSCs on the engineered fibrin scaffolds are also assessed in vitro. These results show that the NPS@Fg promotes the differentiation of EMSCs into neuronal lineage cells, which may also contribute to the therapeutic outcome of the NPS@Fg+EMSCs strategy. After transplantation NPS@Fg+EMSCs into sciatic nerve defects in rats, nerve recovery is assessed up to 12 weeks postinjury. In vivo experiments show that the combination of NPS crosslinked fibrin scaffolds with EMSCs can significantly accelerate nerve healing and improve morphological repair. In the study, NPS@Fg+EMSCs may represent a new potential strategy for peripheral nerve reconstruction.

The influence of reinnervation on the results of peripheral nerve repair after injuries

Abstract Introduction Research on the possibility of increasing the effects of after-injury reconstruction of peripheral nerves conducted in the Department of Physiology at ŚUM resulted in the development of a new method of reconstruction after peripheral nerve injuries. In this new method, we used 7-day predegenerated in situ sural nerve grafts. In clinical assessment, we concluded that recovery in motor, sensory and vegetative function after peripheral nerve injury treatment is better with the use of predegenerated grafts. The latent efficacy of reconstruction was measured months or years after reconstruction. In that amount of time, denervated synaptic sites in muscles can be reinnervated by nearby healthy non-injured nerves. It could increase motor, sensory, or vegetative function, irrespective of the effects of chirurgical treatment. We decided to investigate whether the circumstances may influence the latent efficiency of the new method of reconstruction. Materials and Methods Experiments were carried out on 32 patients in The Department of Neurosurgery Medical University of Silesia. Twenty patients were operated on with a predegenerated (P) implant, and 12 patients operated in the traditional method (T). As a result, 25% of patients’ reinnervation from healthy nearby nerves in the area supplied by reconstructed nerves was present. In group P, reinnervation appeared in 7 of 20 patients (35%) and in group T, in 1 from 12 (8.33%) cases. Results Results of the examinations were counted statistically in both groups. Conclusion Reinnervation from nearby healthy non-injured nerves positively influences the results of human peripheral nerve reconstruction.

Use of acellular dermal matrix in peripheral nerve reconstruction: an experimental study on rat sciatic nerve defect

Background In patients with nerve tissue defects, the use of autologous nerve grafts is the standard method of treatment. Alternatives to autologous, nerve grafts have attracted the attention of reconstructive surgeons. In this study, the results of nerve repairs using acellular dermal matrix (ADM) in an experimental rat sciatic nerve defect model are presented. Methods Thirty-six Sprague-Dawley rats were randomized into 5 groups: Group 1: control group, Group 2: negative control group (n = 6), Group 3: autologous nerve graft group (n = 10), Group 4: donor site entubulated with ADM group (n = 10); and Group 5: nerve graft entubulated with ADM group (n = 10). The animals in each group were evaluated for electrophysiologic functions, gastrocnemius muscle weight and histomorphology on the 3rd and 6th month. Results The compound muscle action potential was observed to be distinctly lower in Groups 3, 4 and 5 in comparison to the control group. In Group 4, the gastrocnemius ratio (GCR) values on the 6th month were statistically significantly lower than the GCR values in Group 3 and Group 5, The histological scores and myelinated axonal counts in Group 5 were statistically significantly higher than the values in Group 3 and Group 4. Conclusion The results of this study showed that wrapping ADM around nerve grafts resulted in better outcomes with respect to nerve healing.

The application of collagen in the repair of peripheral nerve defect.

Collagen is a natural polymer expressed in the extracellular matrix of the peripheral nervous system. It has become increasingly crucial in peripheral nerve reconstruction as it was involved in regulating Schwann cell behaviors, maintaining peripheral nerve functions during peripheral nerve development, and being strongly upregulated after nerve injury to promote peripheral nerve regeneration. Moreover, its biological properties, such as low immunogenicity, excellent biocompatibility, and biodegradability make it a suitable biomaterial for peripheral nerve repair. Collagen provides a suitable microenvironment to support Schwann cells’ growth, proliferation, and migration, thereby improving the regeneration and functional recovery of peripheral nerves. This review aims to summarize the characteristics of collagen as a biomaterial, analyze its role in peripheral nerve regeneration, and provide a detailed overview of the recent advances concerning the optimization of collagen nerve conduits in terms of physical properties and structure, as well as the application of the combination with the bioactive component in peripheral nerve regeneration.

Contemporary Approaches to Peripheral Nerve Surgery

“State of the Art” Learning Objectives: This manuscript serves to provide the reader with a general overview of the contemporary approaches to peripheral nerve reconstruction as the field has undergone considerable advancement over the last 3 decades. The learning objectives are as follows: To provide the reader with a brief history of peripheral nerve surgery and some of the landmark developments that allow for current peripheral nerve care practices. To outline the considerations and management options for the care of patients with brachial plexopathy, spinal cord injury, and lower extremity peripheral nerve injury. Highlight contemporary surgical techniques to address terminal neuroma and phantom limb pain. Review progressive and future procedures in peripheral nerve care, such as supercharge end-to-side nerve transfers. Discuss rehabilitation techniques for peripheral nerve care.

Effects of regenerative peripheral nerve interface on dorsal root ganglia neurons following peripheral axotomy.

BackgroundLong-term delayed reconstruction of injured peripheral nerves always results in poor recovery. One important reason is retrograde cell death among injured sensory neurons of dorsal root ganglia (DRG). A regenerative peripheral nerve interface (RPNI) was capable of generating new synaptogenesis between the proximal nerve stump and free muscle graft. Meanwhile, sensory receptors within the skeletal muscle can also be readily reinnervated by donor sensory axons, which allows the target muscles to become sources of sensory information for function reconstruction. To date, the effect of RPNI on injured sensory neurons is still unclear. Here, we aim to investigate the potential neuroprotective role of RPNI on sensory DRG neurons after sciatic axotomy in adult rats.Materials and methodsThe sciatic nerves of sixty rats were transected. The rats were randomly divided into three groups following this nerve injury: no treatment (control group, n = 20), nerve stump implantation inside a fully innervated muscle (NSM group, n = 20), or nerve stump implantation inside a free muscle graft (RPNI group, n = 20). At 8 weeks post-axotomy, ipsilateral L4 and L5 DRGs were harvested in each group. Toluidine blue staining was employed to quantify the neuronal densities in DRGs. The neuronal apoptosis index was quantified with TUNEL assay. Western blotting was applied to measure the expressions of Bax, Bcl-2, and neurotrophins (NTs) in ipsilateral DRGs.ResultsThere were significantly higher densities of neurons in ipsilateral DRGs of RPNI group than NSM and control groups at 8 weeks post-axotomy (p < 0.01). Meanwhile, neuronal apoptosis index and the expressions of pro-apoptotic Bax within the ipsilateral DRGs were significantly lower in the RPNI group than those in the control and NSM groups (p < 0.05), while the opposite result was observed in the expression of pro-survival Bcl-2. Furthermore, the expressions of NGF, NT-3, BDNF, and GDNF were also upregulated in the ipsilateral DRGs in the RPNI group (p < 0.01).ConclusionThe present results demonstrate that RPNI could prevent neuronal loss after peripheral axotomy. And the neuroprotection effect has a relationship with the upregulation of NTs in DRGs, such as NGF, NT-3, BDNF, and GDNF. These findings provide an effective therapy for neuroprotection in the delayed repair of the peripheral nerve injury.