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• Comprehensively synthesize the functional features of OECs. • The function and mechanism of OECs in the repair of peripheral nerve injury were discussed. • Application of OECs in the treatment of pathological pain induced by peripheral nerve injury was discussed. Direct or indirect injury of peripheral nerve can lead to sensory and motor dysfunction, which can lead to pathological pain and seriously affect the quality of life and psychosomatic health of patients. While the internal repair function of the body after peripheral nerve injury is limited. Nerve regeneration is the key factor hindering the recovery of nerve function. At present, there is no effective treatment. Therefore, more and more attention have been paid to the development of foreground treatment to achieve functional recovery after peripheral nerve injury, including relief of pathological pain. Cell transplantation strategy is a therapeutic method with development potential in recent years, which can exert endogenous alternative repair by transplanting exogenous functional bioactive cells to the site of nerve injury. Olfactory ensheathing cells (OECs) are a special kind of glial cells, which have the characteristics of continuous renewal and survival. The mechanisms of promoting nerve regeneration and functional repair and relieving pathological pain by transplantation of OECs to peripheral nerve injury include secretion of a variety of neurotrophic factors, axonal regeneration and myelination, immune regulation, anti-inflammation, neuroprotection, promotion of vascular growth and improvement of inflammatory microenvironment around nerve injury. Different studies have shown that OECs combined with biomaterials have made some progress in the treatment of peripheral nerve injury and pathological pain. These biomaterials enhance the therapeutic effect of OECs. Therefore, the functional role of OECs in peripheral nerve injury and pathological pain was discussed in this paper. Although OECs are in the primary stage of exploration in the repair of peripheral nerve injury and the application of pain, but OECs transplantation may become a prospective therapeutic strategy for the treatment of peripheral nerve injury and pathological pain. [ABSTRACT FROM AUTHOR]

• We transplanted embryonic spinal motor neurons (SMNs) into peripheral nerve grafts. • SMNs formed a structure similar to the spinal cord. • The diaphragm was reinnervated. • Electrical stimulation of the nerve graft caused diaphragmatic contraction. • SMN transplantation had an inhibitory effect on the atrophy of denervated muscles. Respiratory muscle paralysis due to trauma or neurodegenerative diseases can have devastating consequences. Only a few studies have investigated the reconstruction of motor function in denervated diaphragms caused by such conditions. Here, we studied the efficacy of transplanting E14 embryonic spinal motor neurons (SMNs) into peripheral nerve grafts for functionally reconstructing a denervated diaphragm in a rat model. The diaphragms of 8-week-old male Fischer 344 rats were first denervated by transecting the phrenic nerves. Subsequently, peripheral nerve grafts taken from the lower limb were used for neurotization of the denervated diaphragms. One week later, fetal E14 SMNs were transplanted into the peripheral nerve grafts. After 3 months, we observed functional contraction of the diaphragm following neuromuscular electrical stimulation (NMES) of the peripheral nerve graft. Additionally, we confirmed that SMN transplantation into the peripheral nerve graft had an inhibitory effect on diaphragm muscle atrophy. The SMNs transplanted into the peripheral nerve grafts formed a structure similar to the spinal cord, and the neuromuscular junction of the denervated diaphragm was reinnervated. These findings suggest the establishment of an ectopic motor neuron pool in the peripheral nerve graft. Free peripheral intra-nerve SMN transplantation in combination with NMES, which can be applied for diaphragmatic pacing, offers novel insights into the development of neuroregenerative therapies for treating life-threatening and intractable respiratory muscle paralysis caused by severe nerve damage and degenerative diseases. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injury (SCI) causes massive death of neurons in the spinal cords and almost complete neurological dysfunctions. Transplantation of neural stem/progenitor cells (NSPCs) is acknowledged as one of the viable SCI treatments for complementing lost neurons and neural network reconstruction. However, administration of NSPCs suffers from extremely low survival rate and uncontrolled differentiation of the transplanted cells, which impairs the therapeutic effects significantly. Herein, NSPCs are encapsulated in decellularized spinal cord matrix (DSCM) microgels using a customized microfluidic system, then the obtained NSPCs‐encapsulated DSCM microgels (NSPC@DSCM‐MGs) are subjected to neuronal differentiation induction. Consequently, the resulting pre‐mature 3D neural spheroids are injected into severely contused spinal cords in rats. The DSCM microgels effectively protected the transplanted cells from shear damage and the inflammatory microenvironment at the lesion site. The survival and accommodation of the pre‐differentiated NSPC@DSCM‐MGs actively contributed to axonal regeneration, inhibiting glial scar formation, as well as remodeling the microenvironment that facilitated endogenous cell recruitment and neuronal network reconstruction. Consequentially, administration of the neural spheroids led to maintenance of spinal cord integrity, and significantly improved hindlimb locomotor function. This biomaterial‐based transplantation strategy has shown unique assets in cell protection and cell‐fate manipulation, which holds great promise in versatile biomedical applications. [ABSTRACT FROM AUTHOR]

Peripheral facial paralysis represents a disabling condition with serious psychological and social impact. Patients with peripheral facial paralysis have a disfigurement of the face with loss of harmony and symmetry and difficulties in everyday facial functions such as speaking, drinking, laughing, and closing their eyes, with impairment of their quality of life. This paralysis leads to impairment of facial expression, which represents one of the first means of communication, an important aspect of human interaction. This review aims to explore the reanimation techniques for managing peripheral facial paralysis. An analysis of static and dynamic techniques for facial reanimation is provided, including muscle flaps, nerve grafting techniques, and bioengineering solutions. Each technique showed its benefits and drawbacks; despite several options for facial reanimation, no technique has been detected as the gold standard. Therefore, each patient must be evaluated on an individual basis, considering their medical history, age, expectations, and treatment goals, to find the best and most fitting treatment. [ABSTRACT FROM AUTHOR]

The sural nerve provides sensory innervation to the skin on the distal posterolateral third of the lower extremity. The morphological variants are characterized by high variability. However, it most commonly arises from a union of the medial sural cutaneous nerve and the peroneal communicating branch of the common fibular nerve. This article overviews the anatomical and clinical significance of the sural nerve. Despite the remarkable development of genetic diagnostics, sural nerve biopsy is still a very important tool to diagnose peripheral neuropathies such as diabetic, vascular and inflammatory neuropathies. Furthermore, the sural nerve is also commonly transplanted due to its characteristics. Such a procedure is applicable in cases of segmental nerve loss, but it is also used to restore potency in patients after radical prostatectomy. The knowledge of anatomical variants of the sural nerve is also crucial as it allows to minimize its damage during surgical procedures. Furthermore, during an ankle surgery, a nerve block can be used to complement anesthesia. The major aim of this work is to review contributions of the sural nerve to physiological and pathophysiological processes. [ABSTRACT FROM AUTHOR]

Acellular nerve grafts (ANGs) are a promising therapeutic for patients with nerve defects caused by injuries. Conventional decellularization methods utilize a variety of detergents and enzymes. However, these methods have disadvantages, such as long processing times and the presence of detergents that remain on the graft. In this study, we aimed to reduce process time and minimize the risks associated with residual detergents by replacing them with supercritical carbon dioxide (scCO2) and compared the effectiveness to Hudson's decellularization method, which uses several detergents. The dsDNA and the expression of MHC1 and 2 were significantly reduced in both decellularized groups, which confirmed the effective removal of cellular debris. The extracellular matrix proteins and various factors were found to be better preserved in the scCO2 ANGs compared to the detergent-ANGs. We conducted behavioral tests and histological analyses to assess the impact of scCO2 ANGs on peripheral nerve regeneration in animal models. Compared with Hudson's method, the scCO2 method effectively improved the efficacy of peripheral nerve regeneration. Therefore, the decellularization method using scCO2 is not only beneficial for ANG synthesis, but it may also be helpful for therapeutics by enhancing the efficacy of peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

Background/Objectives: Peripheral nerve injuries (PNIs) are a debilitating problem, resulting in diminished quality of life due to the continued presence of both chronic and acute pain. The current standard of practice for the repair of PNIs larger than 10 mm is the use of autologous nerve grafts. Autologous nerve grafts have limitations that often result in outcomes that are not sufficient to remove motor and sensory impairments. Bio-mimetic nanocomposite scaffolds combined with mesenchymal stem cells (MSCs) represent a promising approach for PNIs. In this study, we investigated the potential of an electrospun wrap of polycaprolactone (PCL) + graphene oxide (GO), with and without xenogeneic human adipose tissue-derived MSCs (hADMSCs) to use as a platform for neural tissue engineering. Methods: We evaluated, in vitro and in vivo, the potential of the nerve wrap in providing support for axonal growth. To establish the rat sciatic nerve defect model, a 10 mm long limiting defect was created in the rat sciatic nerve of 18 Lewis rats. Rats treated with the nanocomposites were compared with autograft-treated defects. Gait, histological, and muscle analyses were performed after sacrifice at 12 weeks post-surgery. Results: Our findings demonstrate that hADMSCs had the potential to transdifferentiate into neural lineage and that the nanocomposite successfully delivered hADMSCs to the injury site. Histologically, we show that the PCL + GO nanocomposite with hADMSCs is comparable to the autologous nerve graft, to support and guide axonal growth. Conclusions: The novel PCL + GO nerve wrap and hADMSCs used in this study provide a foundation on which to build upon and generate future strategies for PNI repair. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the functional outcomes of nerve reconstruction for nerve gaps exceeding 7 cm, using sural nerve autografts. The cases primarily involved brachial plexus injuries and peripheral nerve injuries. The most frequent causes of these injuries were motorcycle accidents and workplace incidents, predominantly affecting young individuals. The best outcomes for nerve injuries are achieved through primary coaptation. All the patients in our study underwent delayed nerve reconstruction rather than primary repair for various reasons, resulting in outcomes that were not as favourable as those of primary repair. Despite using avascular nerve grafts to bridge long nerve gaps, many of our patients still experienced meaningful recovery. Motor function recovery outperformed sensory function recovery across all types of reconstructions. Hence, in situations where facilities and expertise for vascularized nerve grafts are unavailable, attempting reconstruction with an extended nerve graft for long nerve gap is justified. [ABSTRACT FROM AUTHOR]

Electrical stimulation has been integrated in recent decades into rehabilitation protocols following neuromuscular injuries. Existing literature supports the utilisation of prolonged or continuous stimulation generated by implantable or transcutaneous devices for chronic pain subsidence and muscle trophism maintenance, which improve outcomes following microsurgical interventions. Newer uses include brief electrical stimulation for peripheral nerve injury. Brief electrical stimulation has shown promise in expediting regeneration of both torn and crushed nerve axons in the murine model and has been incorporated into a limited number of clinical studies. Augmentation of the natural response of an injured peripheral nerve by electrical stimulation has the potential to accelerate regeneration, presumably leading to improved function and clinical outcomes. We review the existing literature on intraoperative utilisation of electrical stimulation to enhance regeneration, such as neural mechanisms of action and their microscopic effect in animal models, as well as results from initial human studies. Level of Evidence: Level V (Therapeutic) [ABSTRACT FROM AUTHOR]

Objectives: For nerve injuries, not amendable to tensionless epineural coaptation of the nerve, autografts are the preferred treatment. Although absorbable sutures are not recommended for nerve repair, there is no evidence that non-absorbable sutures are superior to absorbable sutures. This study aims to assess the effectiveness of non-absorbable monofilament nylon sutures, absorbable monofilament vicryl sutures, and fibrin glue when used for nerve grafting. Methods: Lewis rats (N = 32) were subjected to a sciatic nerve transection and randomly assigned to a group: graft with Nylon, graft with Vicryl, graft with Fibrin Glue, or no graft. Motor function, sensory function, and thermal pain were assessed during a 12-week recovery period, and immunohistochemistry was used to assess macrophage response. Results: At 12 weeks, the Vicryl and Nylon groups had significantly larger ankle angles at to lift off, which is a measure of motor function, compared to injured controls (p < 0.05). Grafted rats displayed no difference in thermal response but hypersensitivity to mechanical stimuli compared to the uninjured hindlimb. The Nylon, Vicryl, and Fibrin Glue groups all had significantly less atrophy of the gastrocnemius muscle compared to injured controls (p < 0.0001). In the Fibrin Glue group, 3/9 grafts did not incorporate. The Nylon group had significantly less (p = 0.0004) axon growth surrounding the suture holes compared to the Vicryl group. There were no differences in the axon counts, motor neurons, or sensory neurons between all grafted rats. Conclusions: These results demonstrate that vicryl sutures work just as well as nylon for nerve recovery after injury and grafting. [ABSTRACT FROM AUTHOR]

Spinal cord (SC) reconstruction (process to reestablish the severed neural continuity at the injury site) may provide better recovery from blunt SC injury (SCI). A miniature swine model of blunt SC compression was used to test the hypothesis that reconstruction of the SC with sural nerve in combination with surgical decompression and stabilization improves functional, macro- and microstructural recovery compared to decompression and stabilization alone. Following blunt T9-T11 SC compression injury, five adult Yucatan gilts randomly received laminectomy and polyethylene glycol (as fusogen) with (n = 3) or without (n = 2) sural nerve graft SC reconstruction. Fusogens are a heterogeneous collection of chemicals that fuse the axon membrane and are currently used to augment epineural coaptation during peripheral nerve graft reconstruction. Outcome measures of recovery included weekly sensory and motor assessments, various measurements obtained from computed tomography (CT) myelograms up to 12 weeks after injury Measurements from postmortem magnetic resonance imaging (MRI) and results from spinal cord histology performed 12 weeks after injury were also reported. Vertebral canal (VC), SC and dural sac (DS) dimensions and areas were quantified on 2-D CT images adjacent to the injury. Effort to stand and response to physical manipulation improved 7 and 9 weeks and 9 and 10 weeks, respectively, after injury in the reconstruction group. Myelogram measures indicated greater T13-T14 VC, smaller SC, and smaller DS dimensions in the reconstruction cohort, and increased DS area increased DS/VC area ratio, and higher contrast migration over time. Spinal cord continuity was evident in 2 gilts in the reconstruction cohort with CT and MRI imaging. At the SCI, microstructural alterations included axonal loss and glial scarring. Better functional outcomes were observed in subjects treated with sural nerve SC reconstruction. Study results support the use of this adult swine model of blunt SCI. Long-term studies with different nerve grafts or fusogens are required to expand upon these findings. [ABSTRACT FROM AUTHOR]

Background. The use of adipose tissue in reconstructive procedures has become popular in the last decades due to the adipose tissue properties of stem cells and mechanical protection. In acute nerve lesions, there have been experimental reports on the use of non-vascularised adipose tissue as an adjuvant for nerve recovery but to our knowledge there is no published research that describes the effect of the pedicled vascularised adipose tissue (pVAT) on acute nerve injuries. Therefore we decided to study the effect of pVAT on nerve regeneration when wrapped around an epineurial coaptation site and for a 5 mm defect of the sciatic nerve from the rat. Methods. The effect of pedicled vascularized adipose tissue (pVAT) on nerve regeneration was studied on the sciatic nerve injury model in twenty-four Wistar rats divided into four groups: epineurial repair; epineurial repair and pVAT; a 5 mm nerve gap bridged by an autograft; a 5 mm nerve gap bridged by a conduit-pVAT (C-pVAT). Automatization injuries, walking track analysis, postoperative extraneural fibrosis and histological analysis were performed three months after the intervention. Results. Although histological and functional nerve regeneration was present in various degrees in all the studied groups, nerve regeneration was not enhanced by the use of the pVAT or C-pVAT. The harvesting of the pVAT flap caused postoperative fibrosis when used as a conduit. Automutilation was not decreased by the use of the pVAT nor a correlation between automutilation and postoperative fibrosis in the studied groups could be established. The postoperative fibrosis did not influence neural regeneration in the pVAT and autograft group. Conclusion. Vascularized adipose tissue did not enhance neural regeneration when used as an adjunct procedure for primary nerve repair and or even as a novel conduit for 5 mm nerve defects in the rat sciatic nerve. [ABSTRACT FROM AUTHOR]

Purpose: Extensive lesions of the brachial plexus, or late cases, require free functional muscle grafts because the expected recovery time exceeds the critical threshold of 1.5 years, beyond which irreversible damage may be expected in the distal nerve stump and in the muscle. The reconstructive concept consists of a two-stage procedure where, in the first step, a nerve transfer is performed (from ipsi- or contralateral donor nerves). In the second step, after successful axonal regeneration within the graft has been confirmed, a free muscle transfer is performed. These grafts often exceed 40 cm in length, particularly for contralateral transfers. The purpose of this study was to assess whether robust motor recovery could be supported by such long nerve grafts. Methods: From April 2004 to April 2023, a total of 327 free functional muscle transfers were performed, the nerve graft length ranging from 0 cm (direct coaptation) to 90 cm (serial grafts). Motor recovery was evaluated 1.5 years after surgery according to the MRC scale. Results: A total of 208 patients were available for follow up. Direct coaptation yielded the best results, with 83% of patients reaching an M3 or M4 level of muscle strength. With the application of long (30–60 cm) grafts, 73% of the patients were classified as M3 or M4. The application of serial nerve grafts, however, only resulted in 18% of patients achieving a motor recovery rating of M3. Conclusions: These findings demonstrate that robust motor regeneration is supported by long (30–60 cm) nerve grafts, whereas serial nerve grafting results in a marked reduction in the quality of regeneration. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a devastating condition that significantly decreases the patient's quality of life. Therefore, treatments that can facilitate nerve regeneration, reduce complications, and increase quality of life are valuable for these patients. In this study, we aimed to assess nerve bypass surgery's feasibility and clinical outcomes by transferring the intercostal nerves into the spinal cord. Eight patients with complete thoracic SCI and delayed presentation more than a year after the injury were analyzed retrospectively. All patients underwent nerve bypass surgery with the transfer of 2 pairs of intercostal nerves from proximal to the injury site to the anterolateral spinal cord, followed by duraplasty with fascia grafting to close the dura. Six of the 8 (75%) patients demonstrated motor and sensory improvements, based on the American SCI Association score. Three patients demonstrated a limited recovery of motor function that could be independently triggered without ICN initiation. Five patients demonstrated evidence of cerebrospinal fluid leakage after surgery; however, only 1 patient complained of a headache. Spinal cord bypass surgery is a potential reconstruction method to treat chronic complete thoracic SCI with functional improvements, and is worth further investigation. [ABSTRACT FROM AUTHOR]

Traumatic and postoperative hemorrhages are life-threatening complications. Ankaferd BloodStopper (ABS) is a potent topical hemostatic agent to stop bleeding. However, ABS is associated with nerve toxicity. The present study aimed to investigate the functional and structural neurodegenerative effects of ABS in a mouse model. A total of 30 male BALB/c mice, aged 6-8 weeks, were randomly divided into control group (no treatment), a sham group (treated with saline) and an experimental group (treated with ABS). In the saline and the ABS groups, the right sciatic nerve was surgically exposed and treated with saline or ABS, respectively. No surgical procedure was performed in the control group. On day 7 post-treatment, functional changes of the sciatic nerve were evaluated by a horizontal ladder rung walking task. Structural changes were assessed with immunohistochemistry. In the horizontal ladder rung walking test, the gait impairment was proportional to the severity of sciatic nerve damage, with the ABS group showing a significantly higher rate of errors than the control and saline groups. Immunohistochemistry demonstrated extensive degeneration and deformation in the axons and myelin sheath of the sciatic nerve in the ABS group. The results provide compelling evidence for the neurotoxicity of ABS. [ABSTRACT FROM AUTHOR]

The regeneration of peripheral nerves after injury is often slow and impaired, which may be associated with weakened and denervated muscles subsequently leading to atrophy. Adipose-derived stem cells (ADSCs) are often regarded as cell-based therapeutic candidate due to their regenerative potential. The study aims to assess the therapeutic efficacy of gene-modified ADSCs on sciatic nerve injury. We lentivirally transduced ADSCs with shRNA-TWIST1 and transplanted modified cells to rats undergoing sciatic nerve transection and repair. Results showed that TWIST1 knockdown accelerated functional recovery of rats with sciatic nerve injury as faster nerve conduction velocity and higher wire hang scores obtained by rats transplanted with TWIST1-silenced ADSCs than scramble ADSCs. Although the rats experienced degenerated axons and decreased myelin sheath thickness after sciatic nerve injury 8 weeks after operation, those transplanted with TWIST1-silenced ADSCs exhibited more signs of regenerated nerve fibers surrounded by newly formed myelin sheaths than those with scramble ADSCs. The rats transplanted with TWIST1-silenced ADSCs presented increased expressions of neurotrophic factors including neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) in the sciatic nerves than those with scramble ADSCs. These results suggest that genetically modifying TWIST1 in ADSCs could facilitate peripheral nerve repair after injury in a more efficient way than that with ADSCs alone. [ABSTRACT FROM AUTHOR]

Following nipple-sparing mastectomy (NSM), patients commonly experience significant impairment or total loss of nipple sensitivity, which negatively impacts the patients' quality of life, whereas patients who retain nipple sensation postoperatively experience enhanced physical, psychosocial, and sexual well-being. Reinnervation techniques such as nerve allografting have been utilized to retain sensation. Despite the benefits of nerve allografts, such as lack of donor site morbidity, ease of use, and potentially shorter surgery time, there are shortcomings, such as the cost of commercially available acellular nerve allografts, and, most importantly, decreased sensory and motor function recovery for acellular nerve allografts with a diameter greater than 3 mm or a length greater than 50 mm. We present a technique where we performed immediate implant-based breast reconstruction combined with nipple–areola complex reinnervation using an autologous nerve graft. Following the procedure, the patient had improved sensory outcomes in the reconstructed breast and good quality-of-life indices. This report highlights the potential for sural nerve autografts in restoring breast sensation following mastectomy. [ABSTRACT FROM AUTHOR]

Purpose: A systematic review to identify treatment approaches for the management of pain following peripheral nerve injury. Methods: A published literature search was performed for the concepts of peripheral nerve injury and pain management with related synonyms. The strategies were created using a combination of controlled vocabulary terms and keywords and were executed in Embase.com, Ovid-Medline All, and Scopus from database inception. Database searches were completed on August 22, 2023. Results: The initial search resulted in a total of 1,793 citations. In total, 724 duplicates were removed, leaving 1,069 unique citations remaining for analysis. This review excluded all papers that were not specific to pain following peripheral nerve injury. Case and cohort studies (n < 5) were also excluded. Thirty-two articles on pain management strategies after peripheral nerve injury remained, with years of publication ranging from 1981 to 2023. An additional four articles were identified by manual search. Of the 36 articles reviewed, 15 articles reported on the approach to the treatment of pain after a peripheral nerve injury, and the other 22 articles consisted of cohort and case series studies. Conclusions: There is a lack of literature describing efficacy of various treatment strategies for pain following peripheral nerve injuries. Few studies provide clear, stepwise clinical guidance for practicing physicians and other health care providers on the treatment of these complicated patients.

Purpose: Vascularized nerve grafts (VNGs) have been proposed as encouraging alternatives to conventional nerve grafting; however, there is ongoing debate regarding the clinical advantages of the approach compared with standard grafting. This review aims to gather and analyze reported cases of upper extremity nerve repair using VNGs documented in the published literature. Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed/MEDLINE, Embase, and Cochrane were searched. Inclusion criteria for this review included the following: (1) human subjects or cadaveric studies, (2) describing a vascularized nerve grafting procedure or suggesting a nerve and vascular supply for a potential vascularized nerve graft, and (3) upper extremity nerve repair in clinical studies. Results: Data were extracted from 45 clinical studies. Of 535 patients, the most common injury pattern was root avulsion and rupture (88.7%). The most utilized VNG was the ulnar nerve (72.8%), followed by nerve to long head of triceps (8.8%) and sural nerve (8.2%); most common recipients were median (57.6%), axillary (12.5%), and musculocutaneous nerves (11.9%). Between patients who had medical research council scale scores, 69% had functional (M3 and above) motor and 72.7% sensory (S3

• The therapeutic effects of different types of cell transplantation (Neural stem cells, Schwann cells, olfactory ensheathing cells and mesenchymal stem cells) in the application of NPP were discussed comprehensively. • The application value of cell transplantation in NPP clinical trial was discussed. • The problems and challenges of cell transplantation in the treatment of NPP were discussed. Nerve injury can not only lead to sensory and motor dysfunction, but also be complicated with neuropathic pain (NPP), which brings great psychosomatic injury to patients. At present, there is no effective treatment for NPP. Based on the functional characteristics of cell transplantation in nerve regeneration and injury repair, cell therapy has been used in the exploratory treatment of NPP and has become a promising treatment of NPP. In this article, we discuss the current mainstream cell types for the treatment of NPP, including Schwann cells, olfactory ensheathing cells, neural stem cells and mesenchymal stem cells in the treatment of NPP. These bioactive cells transplanted into the host have pharmacological properties of decreasing pain threshold and relieving NPP by exerting nutritional support, neuroprotection, immune regulation, promoting axonal regeneration, and remyelination. Cell transplantation can also change the microenvironment around the nerve injury, which is conducive to the survival of neurons. It can effectively relieve pain by repairing the injured nerve and rebuilding the nerve function. At present, some preclinical and clinical studies have shown that some encouraging results have been achieved in NPP treatment based on cell transplantation. Therefore, we discussed the feasible strategy of cell transplantation as a treatment of NPP and the problems and challenges that need to be solved in the current application of cell transplantation in NPP therapy. [ABSTRACT FROM AUTHOR]

Purpose: Facial paralysis results from congenital or acquired facial nerve damage, leading to significant cosmetic and functional deficits. Surgical resection of parotid and midface tumors can cause facial paralysis, necessitating effective treatment strategies. This review addresses the challenge of restoring movement and function in late-stage facial paralysis, focusing on dynamic repair techniques involving nerve and muscle transplantation. Methods: The review encompasses studies on dynamic repair surgery for late facial paralysis, including techniques such as local muscle flap with pedicle transfer, vascularized nerve flap with pedicle transfer, and multiple muscle flap procedures. A systematic literature search was conducted using PubMed, Web of Science, and Google Scholar, covering studies from 2000 to 2024. Keywords included "dynamic repair", "late-stage facial paralysis", "nerve and muscle transplantation", "muscle flap", and "tendon transposition". Included were clinical studies, systematic reviews, and meta-analyses reporting surgical outcomes. Exclusion criteria included studies with insufficient data and non-peer-reviewed articles. Results: Dynamic repair techniques involving nerve and muscle transplantation are essential for treating late-stage facial paralysis. Each surgical method has strengths and limitations. The masseter muscle flap demonstrates high success rates, although it can cause horizontal tension and jaw contour issues. The temporalis muscle flap is effective for smile restoration but may lead to temporal concavity. The gracilis muscle flap is widely used, especially with dual nerve innervation, showing high success in spontaneous smiles but requiring a longer recovery period. The latissimus dorsi flap is effective but can cause edema and shoulder issues. The serratus anterior free flap offers flexibility with precise vector positioning but may not achieve adequate lip elevation and can cause cheek swelling. Combined multi-flap surgeries provide more natural facial expressions but increase surgical complexity and require advanced microsurgical skills. Conclusions: Dual nerve innervation shows promise for restoring spontaneous smiles. One-stage surgery offers faster recovery and reduced financial burden. Comprehensive patient evaluation is crucial to select the most suitable surgical method. Dynamic repair techniques involving nerve and muscle transplantation provide effective solutions for restoring function and aesthetics in late-stage facial paralysis. Future research should focus on long-term outcomes, patient satisfaction, and standardizing surgical protocols to optimize treatment strategies. [ABSTRACT FROM AUTHOR]

Neurosurgical interventions and trauma are common causes of damage to the optic nerve. This determines the relevance of research for solutions aimed at restoration of the nerve's anatomical integrity, electrical conductivity, and subsequently – restoration of its function. Restore a damaged (cut) optic nerve using n. suralis autograft in vivo. The experiment involved reconstruction of the optic nerve through injury modulation, graft placement and restored nerve harvest and evaluation. Injury modulation included removal of a fragment of the optic nerve. Autograft harvesting and placement involved resection of a fragment of the sural (sensory) nerve and its subsequent anastomosis in place of the removed fragment of the optic nerve. As an experimental model, a rabbit of the "Burgundy" breed was used. The animal was previously examined for the presence of infectious and other diseases to confirm its health. Four months post operatively when stimulating the operated right eye, low-amplitude components altered in shape are registered. Thus, signs of mild restoration of electrical conductivity on the treated optic nerve were seen. Our initial experience shows the technical feasibility of reconstructing the optic nerve using an autograft, the possibility of axonal growth through the graft and, in the future, using this method for direct optic nerve reconstruction, as well as a bypass method for damage to the optic nerve with various tumor diseases of the optic nerve, tumors of the chiasmatic-sellar localization, orbital injuries. [ABSTRACT FROM AUTHOR]

Extrarenal extracranial malignant rhabdoid tumour (MRT) is a rare and highly aggressive tumour representing <1% of paediatric soft tissue malignancies. Only a few cases of MRT of the thigh arising from the sciatic nerve have been reported in medical literature to date. A 5-year-old girl presented with progressively increasing painless lump in the posterior aspect of the left thigh. A contrast-enhanced magnetic resonance imaging (MRI) of the left thigh showed a 4.7 × 5 × 10.5 cm well-marginated, lobulated, homogeneously enhancing lesion in the posterior compartment of the left thigh along the course of the sciatic nerve. She underwent en bloc excision of the left sciatic nerve tumour and end-to-end anastomosis of the left sciatic nerve with a right sural nerve graft. Histopathological and immunohistochemical examination of the surgical specimen revealed a malignant rhabdoid tumour. INI-1 immunoexpression was lost in the tumour cells. The metastatic workup was essentially normal. Subsequently, she received post-operative radiotherapy to the tumour bed (50.4 Gray in 28 fractions over 5.5 weeks) followed by six cycles of multiagent chemotherapy with ICE (Ifosfamide, Carboplatin, and Etoposide) regimen. On the last follow-up visit, 20 months after surgery, she was in complete clinical and radiological response. Aggressive multimodality management comprising radical resection of tumour, post-operative radiotherapy to the tumour bed, and multiagent chemotherapy with ICE regimen can lead to favourable outcomes in patients with this rare tumour. [ABSTRACT FROM AUTHOR]

Background: Injury of peripheral nerve capable of regeneration with much poorer prognosis affects people's life quality. The recovery of nerve function after transplantation for peripheral nerve injury remain a worldwide problem. Silicon-induced biofilms as vascularized biological conduits can promote nerve regeneration by encapsulating autologous or allogeneic nerve graft. Objective: We proposed to explore the effect of silicon-induced biofilms on nerves regeneration and whether the VEGF/VEGFR2/ERK pathway was involved in the present study. Methods: Biofilms around the transplanted nerves in peripheral nerve injury rats were induced by silicon. Vascularization and proteins related to VEGF/VEGFR2/ERK were measured. Pathology and morphology of nerves were investigated after encapsulating the transplanted nerves by silicon-induced biofilms. Results: Our results indicated that the biofilms induced by silicon for 6 weeks showed the most intensive vascularization and the optimal effect on nerve regeneration. Moreover, silicon-induced biofilms for 4, 6 and 8 weeks could significantly secrete VEGF with the highest content at week 6 after induction. VEGFR2, VEGF, p-VEGFR2, ERK1, ERK2, p-ERK1 and p-ERK2 were expressed in the biofilms. p-VEGFR2, p-ERK1 and p-ERK2 expression were different at each time point and significantly increased at week 6 compared with that at week 4 or week 8 which was consistent with that 6 week of was the optimum time for biofilms induction to improve the nerve repair after peripheral nerve injury. Conclusion: Our results suggested that combination of silicon-induced autologous vascularized biofilm and autologous transplantation may promote the repair of rat sciatic nerve defect quickly through VEGF/VEGFR2/ERK pathway. [ABSTRACT FROM AUTHOR]

Peripheral nerve defect are common clinical problem caused by trauma or other diseases, often leading to the loss of sensory and motor function in patients. Autologous nerve transplantation has been the gold standard for repairing peripheral nerve defects, but its clinical application is limited due to insufficient donor tissue. In recent years, the application of tissue engineering methods to synthesize nerve conduits for treating peripheral nerve defect has become a current research focus. This study introduces a novel approach for treating peripheral nerve defects using a tissue‐engineered PLCL/SF/NGF@TA‐PPy‐RGD conduit. The conduit was fabricated by combining electrospun PLCL/SF with an NGF‐loaded conductive TA‐PPy‐RGD gel. The gel, synthesized from RGD‐modified tannic acid (TA) and polypyrrole (PPy), provides growth anchor points for nerve cells. In vitro results showed that this hybrid conduit could enhance PC12 cell proliferation, migration, and reduce apoptosis under oxidative stress. Furthermore, the conduit activated the PI3K/AKT signalling pathway in PC12 cells. In a rat model of sciatic nerve defect, the PLCL/SF/NGF@TA‐PPy‐RGD conduit significantly improved motor function, gastrocnemius muscle function, and myelin sheath axon thickness, comparable to autologous nerve transplantation. It also promoted angiogenesis around the nerve defect. This study suggests that PLCL/SF/NGF@TA‐PPy‐RGD conduits provide a conducive environment for nerve regeneration, offering a new strategy for peripheral nerve defect treatment, this study provided theoretical basis and new strategies for the research and treatment of peripheral nerve defect. [ABSTRACT FROM AUTHOR]

Complicated peripheral nerve injuries or defects, especially at branching sites, remain a prominent clinical challenge after the application of different treatment strategies. Current nerve grafts fail to match the expected shape and size for delicate and precise branched nerve repair on a case-by-case basis, and there is a lack of geometrical and microscale regenerative navigation. In this study, we develop a sugar painting-inspired individualized multilevel epi-/peri-/endoneurium-mimetic device (SpinMed) to customize natural cues, featuring a selectively protective outer sheath and an instructive core, to support rapid vascular reconstruction and consequent efficient neurite extension along the defect area. The biomimetic perineurium dictates host-guest crosslinking in which new vessels secrete multimerin 1 binding to the fibroin filler surface as an anchor, contributing to the biological endoneurium that promotes Schwann cell homing and remyelination. SpinMed implantation into rat sciatic nerve defects yields a satisfactory outcome in terms of structural reconstruction, with sensory and locomotive function restoration. We further customize SpinMed grafts based on anatomy and digital imaging, achieving rapid repair of the nerve trunk and branches superior to that achieved by autografts and decellularized grafts in a specific beagle nerve defect model, with reliable biosafety. Overall, this intelligent art-inspired biomimetic design offers a facile way to customize sophisticated high-performance nerve grafts and holds great potential for application in translational regenerative medicine. Nerve grafts often fail to match the expected shape and size for branched nerve repair. Here, the authors fabricate a sugar painting-inspired individualized multilevel epi-/peri-/endoneurium-mimetic device to achieve efficient regeneration of neural fibers. [ABSTRACT FROM AUTHOR]

Care for patients with peripheral nerve injury is multifaceted, as traditional methods are not devoid of limitations. Although the utilization of neural conduits shows promise as a therapeutic modality for peripheral nerve injury, its efficacy as a standalone intervention is limited. Hence, there is a pressing need to investigate a composite multifunctional neural conduit as an alternative treatment for peripheral nerve injury. In this study, a BDNF-loaded chitosanbased mimetic mussel polymer conduit was prepared. Its unique adhesion characteristics allow it to be suture-free, improve the microenvironment of the injury site, and have good antibacterial properties. Researchers utilized a rat sciatic nerve injury model to evaluate the progression of nerve regeneration at the 12-week postoperative stage. The findings of this study indicate that the chitosan-based mimetic mussel polymer conduit loaded with BDNF had a substantial positive effect on myelination and axon outgrowth. The observed impact demonstrated a favorable outcome in terms of sciatic nerve regeneration and subsequent functional restoration in rats with a 15-mm gap. Hence, this approach is promising for nerve tissue regeneration during peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury is a prevalent clinical problem that often leads to lifelong disability and reduced quality of life. Although peripheral nerves can regenerate, recovery after severe injury is slow and incomplete. The current gold standard treatment, autologous nerve transplantation, has limitations including donor site morbidity and poor functional outcomes, highlighting the need for improved repair strategies. We developed a reproducible in vitro hollow channel collagen gel construct to investigate peripheral nerve regeneration (PNR) by exploring the influence of key extracellular matrix (ECM) proteins on axonal growth and regeneration. Channels were coated with ECM proteins: collagen IV, laminin, or fibronectin and seeded with dorsal root ganglia (DRG) collected from E16 rat embryos to compare the ability of the ECM proteins to enhance axonal growth. Robust axonal extension and Schwann cell (SC) infiltration were observed in fibronectin-coated channels, suggesting its superiority over other ECM proteins. Differential effects of ECM proteins on axons and SCs indicated direct growth stimulation beyond SC-mediated guidance. In vitro laceration injury modeling further confirmed fibronectin's superior pro-regenerative effects, showcasing its potential in enhancing axonal regrowth post-injury. Advancing in vitro modeling that closely replicates native microenvironments will accelerate progress in overcoming the limitations of current nerve repair approaches. [ABSTRACT FROM AUTHOR]

BACKGROUND: Spinal cord injury not only causes serious physical and psychological injuries to patients but also brings a heavy economic burden to society. Spinal cord injury is initially triggered by mechanical trauma, followed by secondary injuries, and as the disease progresses, a glial scar develops. OBJECTIVE: To summarize the pathological process of spinal cord injury and strategies for stem cell transplantation to repair spinal cord injury, aiming to provide the best protocol for treating spinal cord injury. METHODS: Computer search was used to search PubMed and CNKI databases. Chinese search terms were “stem cell transplantation, spinal cord injury”. English search terms were “stem cell, spinal cord injury, spinal cord, mesenchymal stem cells, neural stem cells, pathophysiology, clinical trial, primary injury, secondary injury”. The literature was screened according to the inclusion and exclusion criteria. Finally, 91 articles were included for review analysis. RESULTS AND CONCLUSION: (1) The strategies for repairing spinal cord injury through stem cell transplantation can be divided into exogenous stem cell transplantation and endogenous stem cell transplantation. The exogenous stem cell transplantation strategy for the treatment of spinal cord injury is divided into four kinds: injecting stem cells into the site of injury; transplantation of biomaterials loaded with stem cells; fetal tissue transplantation; transplantation of engineered neural network tissue or spinal cord-like tissue. (2) Compared with a single treatment method, combination therapy can more effectively promote nerve regeneration and spinal cord function recovery. (3) Microenvironment regulating the injury site, magnetic stimulation, electrical stimulation, epidural oscillating electric field stimulation, transcription factor overexpression and rehabilitation therapy can be combined with stem cell transplantation for combination therapy, thereby promoting the recovery of spinal cord function. [ABSTRACT FROM AUTHOR]

Background/aim: In the literature, almost all of the nerve conduits proposed for obtaining better nerve recovery were applied as graft materials. In this study, we aimed to propose a new nerve conduit model with a flap pattern and evaluate the effect of a pedicled vascularized jejunal flap on nerve regeneration after wrapping it around a sciatic nerve. Materials and methods: A total of 90 Wistar albino rats were randomly divided into nine groups with 10 rats in each. The first three groups constituted the control groups, whereas Groups 4-6 were the jejunum conduit (JC)-applied groups. A mucosa-resected JC (MRJC) was applied in Groups 7 and 8. Epineurial neurorrhaphy was performed in Groups 1, 4, and 7; repair with a nerve graft was applied in Groups 2, 5, and 8; and a 1-cm-long nerve defect was created in Groups 3, 6, and 9. After 2 months of follow-up, nerve regeneration was assessed by statistical analyses of the Sciatic Functional Index (SFI) and histopathological evaluation. Results: The MRJC groups had significantly better results in terms of SFI (p = 0.005). Statistical differences in axonal degeneration, axonal density, myelination, and disorganization were found between all control groups and MRJC groups (p = 0.022, p = 0.001, p = 0.001, and p = 0.039, respectively). Conclusion: In this study, the feasibility of wrapping around the nerve repair zones of pedicled autologous flaps designed in a tubular fashion was observed in a small rat model. The findings must be further validated with larger animals before clinical testing. [ABSTRACT FROM AUTHOR]

Introduction Facial trauma can cause damage to the facial nerve, which can have negative effects on function, aesthetics, and quality of life if left untreated. Objective To evaluate the effectiveness of peripheral facial nerve direct end-to-end anastomosis and/or nerve grafting surgery for patients with facial nerve injury after facial trauma. Methods Fifty-nine patients with peripheral facial nerve paralysis after facial injuries underwent facial nerve rehabilitation surgery from November 2017 to December 2021 at Ho Chi Minh City National Hospital of Odontology. Results All 59 cases of facial trauma with damage to the peripheral facial nerve underwent facial nerve reconstruction surgery within 8 weeks of the injury. Of these cases, 25/59 (42.3%) had end-to-end anastomosis, 22/59 (37.3%) had nerve grafting, and 12/59 (20.4%) had a combination of nerve grafting and end-to-end anastomosis. After surgery, the rates of moderate and good recovery were 78.4% and 11.8%, respectively. All facial paralysis measurements showed statistically significant improvement after surgery, including the Facial Nerve Grading Scale 2.0 (FNGS 2.0) score, the Facial Clinimetric Evaluation (FaCE) scale, and electroneurography. The rate of synkinesis after surgery was 34%. Patient follow-up postoperatively ranged from 6 to > 36 months; 51 out of 59 patients (86.4%) were followed-up for at least 12 months or longer. Conclusion Nerve rehabilitation surgery including direct end-to-end anastomosis and nerve grafting is effective in cases of peripheral facial nerve injury following facial trauma. The surgery helps restore nerve conduction and improve facial paralysis. [ABSTRACT FROM AUTHOR]

The regenerative microenvironment after peripheral nerve injury is imbalanced and difficult to rebalance, which is mainly affected by inflammation, oxidative stress, and inadequate blood supply. The difficulty in remodeling the nerve regeneration microenvironment is the main reason for slow nerve regeneration. Traditional drug treatments have certain limitations, such as difficulty in penetrating the blood-nerve barrier and lack of pleiotropic effects. Therefore, there is an urgent need to build multifunctional nerve grafts that can effectively regulate the regenerative microenvironment and promote nerve regeneration. Nitric oxide (NO), a highly effective gas transmitter with diatomic radicals, is an important regulator of axonal growth and migration, synaptic plasticity, proliferation of neural precursor cells, and neuronal survival. Moreover, NO provides potential anti-inflammation, anti-oxidation, and blood vessel promotion applications. However, excess NO may cause cell death and neuroinflammatory cell damage. The prerequisite for NO treatment of peripheral nerve injury is that it is gradually released over time. In this study, we constructed an injectable NO slow-release system with two main components, including macromolecular NO donor nanoparticles (mPEG-P(MSNO-EG) nanoparticles, NO-NPs) and a carrier for the nanoparticles, mPEG-PA-PP injectable temperature-sensitive hydrogel. Due to the multiple physiological regulation of NO and better physiological barrier penetration, the conduit effectively regulates the inflammatory response and oxidative stress of damaged peripheral nerves, promotes nerve vascularization, and nerve regeneration and docking, accelerating the nerve regeneration process. The slow regeneration speed of peripheral nerves is mainly due to the destruction of the regeneration microenvironment. Neural conduits with drug delivery capabilities have the potential to improve the microenvironment of nerve regeneration. However, traditional drugs are hindered by the blood nerve barrier and cannot effectively target the injured area. NO, an endogenous gas signaling molecule, can freely cross the blood nerve barrier and act on target cells. However, excessive NO can lead to cell apoptosis. In this study, a NO sustained-release system was constructed to regulate the microenvironment of nerve regeneration through various pathways and promote nerve regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

This case report describes the treatment of a postoperative painful neuroma of the tibial nerve using an autologous nerve graft in a dog. The patient presented with sudden non–weight-bearing lameness 10 days after iatrogenic tibial nerve injury during preparation of a reverse saphenous conduit flap. The dog showed severe pain at the surgical site without nerve deficits. A magnetic resonance imaging examination revealed an enlarged tibial nerve at the injury site, consistent with a neuroma. Analgesics were administered over 11 days, but the patient remained in severe pain and non–weight-bearing. Therefore, surgical resection was recommended. The fusiform neuroma was resected microsurgically, and a saphenous nerve graft was transplanted using an epineural nerve repair technique. Histopathological examination was consistent with a neuroma. The dog showed immediate pain relief and weight-bearing the day after surgery with normal motor function. The dog made a full recovery by the last follow-up 6 mo after surgery. If patients develop pain and lameness following surgery or nerve injury, neuroma formation must be considered, even shortly after surgery. Microsurgical resection and autologous nerve transplantation using an epineural nerve repair technique is a viable method to treat painful neuromas and minimize the risk for recurrence in dogs. [ABSTRACT FROM AUTHOR]

A study was undertaken to establish the incidence and types of traumatic brachial plexus injury in the Scottish population over a 10-year period between 2011 and 2020, using a prospectively compiled database. There were 425 injuries, of which 328 were infraclavicular and 97 were supraclavicular. Infraclavicular injury associated with anterior shoulder dislocation was the most common subtype (n = 166). The most common mechanism of injury was fall from standing height (n = 160). In total, 45 operations were performed for supraclavicular and 89 for infraclavicular injuries, with 54 requiring nerve repairs with grafts, transfers or suture. The incidence was 0.8/100,000 per year, with numbers of infraclavicular injuries increasing. The majority were low-energy infraclavicular injuries, not requiring surgery. Supraclavicular injuries were less common but associated with high-energy trauma and likely to require nerve repair. This study gives information on epidemiology and resource requirement for brachial plexus injuries in this defined population, which is likely to be representative of Western European countries with similar demographics. Level of evidence: III [ABSTRACT FROM AUTHOR]

Background: Trigeminal trophic syndrome (TTS) is a rare condition caused by damage to the trigeminal nervous system, resulting in sensory disturbances and ulcers on the face. Treating TTS is complex and often requires medical or surgical intervention like flap reconstruction. However, there is limited research on surgical treatments for TTS ulcers. Methods: We report the case of a 19‐year‐old man with TTS. We employed an innovative surgical technique involving dual cross‐face nerve grafts. In the initial procedure, corneal neuralization was accomplished using supraorbital and cross‐face infraorbital nerve graft. The subsequent operation utilized auricular composite tissue flap transplantation repair and cross‐face mental nerve graft. Results: This procedure led to rapid and sustained healing, as well as aesthetic improvement. Conclusion: Cross‐face nerve grafts is a promising tool in the treatment of refractory ulcers caused by diseases such as TTS. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries present a complex clinical challenge, requiring a nuanced approach in surgical management. The consequences of injury vary, with sometimes severe disability, and a risk of lifelong pain for the individual. For late management, the choice of surgical techniques available range from neurolysis and nerve grafting to tendon and nerve transfers. The choice of technique utilized demands an in-depth understanding of the anatomy, patient demographics and the time elapsed since injury for optimized outcomes. This paper focuses on injuries to the radial, median and ulnar nerves, outlining the authors' approach to these injuries. Level of evidence: IV [ABSTRACT FROM AUTHOR]

From the first surgical repair of a nerve in the 6th century, progress in the field of peripheral nerve surgery has marched on; at first slowly but today at great pace. Whether performing primary neurorrhaphy or managing multiple large nerve defects, the modern nerve surgeon has an extensive range of tools, techniques and choices available to them. Continuous innovation in surgical equipment and technique has enabled the maturation of autografting as a gold standard for reconstruction and welcomed the era of nerve transfer techniques all while bioengineers have continued to add to our armamentarium with implantable devices, such as conduits and acellular allografts. We provide the reader a concise and up-to-date summary of the techniques available to them, and the evidence base for their use when managing nerve transection including current use and applicability of nerve transfer procedures. [ABSTRACT FROM AUTHOR]

Nerve grafting, tendon transfer and joint fusion are routinely used to improve the upper limb function in patients with brachial plexus palsies. Newer techniques have been developed that provide additional options for reconstruction. Nerve transfer is a tool for restoring upper limb function in total root avulsions where nerve grafting is not possible. In partial brachial plexus injuries, nerve transfers can greatly improve shoulder, elbow, wrist and hand function. Intraoperative electrical stimulation can be used to diagnose precisely which nerve is injured and to choose which nerve fascicles should be transferred. Finally, measuring the postoperative outcome can improve the evaluation of our techniques. The aim of this article was to present the current techniques used to treat patients with brachial plexus injury. [ABSTRACT FROM AUTHOR]

Distal nerve transfer is a refined surgical technique involving the redirection of healthy sacrificable nerves from one part of the body to reinstate function in another area afflicted by paralysis or injury. This approach is particularly valuable when the original nerves are extensively damaged and standard repair methods, such as direct suturing or grafting, may be insufficient. As the nerve coaptation is close to the recipient muscles or skin, distal nerve transfers reduce the time to reinnervation. The harvesting of nerves for transfer should usually result in minimal or no donor morbidity, as any anticipated loss of function is compensated for by adjacent muscles or overlapping cutaneous territory. Recent years have witnessed notable progress in nerve transfer procedures, markedly enhancing the outcomes of upper limb reconstruction for conditions encompassing peripheral nerve, brachial plexus and spinal cord injuries. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to investigate the relationship between neuropathic pain and CREB-binding protein (CBP) and methyl-CpG-binding protein 2 (MeCP2) expression levels in a rat model with spared nerve injury (SNI). Materials and Methods: Rat (male Sprague-Dawley white rats) models with surgical SNI (n = 6) were prepared, and naive rats (n = 5) were used as controls. The expression levels of CBP and MeCP2 in the spinal cord and dorsal root ganglion (DRG) were compared through immunohistochemistry at 7 and 14 days after surgery. The relationship between neuropathic pain and CBP/MeCP2 was also analyzed through intrathecal siRNA administration. Results: SNI induced a significant increase in the number of CBPs in L4 compared with contralateral DRG as well as with naive rats. The number of MeCP2 cells in the dorsal horn on the ipsilateral side decreased significantly compared with the contralateral dorsal horn and the control group. SNI induced a significant decrease in the number of MeCP2 neurons in the L4 ipsilateral DRG compared with the contralateral DRG and naive rats. The intrathecal injection of CBP siRNA significantly inhibited mechanical allodynia induced by SNI compared with non-targeting siRNA treatment. MeCP2 siRNA injection showed no significant effect on mechanical allodynia. Conclusions: The results suggest that CBP and MeCP2 may play an important role in the generation of neuropathic pain following peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Peripheral nerve deficits give rise to motor and sensory impairments within the limb. The clinical restoration of extensive segmental nerve defects through autologous nerve transplantation often encounters challenges such as axonal mismatch and suboptimal functional recovery. These issues may stem from the limited regenerative capacity of proximal axons and the subsequent Wallerian degeneration of distal axons. To achieve the integration of sensory and motor functions, a spatially differential plasmid DNA (pDNA) dual‐delivery nanohydrogel conduit scaffold is devised. This innovative scaffold facilitates the localized administration of the transforming growth factor β (TGF‐β) gene in the proximal region to accelerate nerve regeneration, while simultaneously delivering nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) to the distal region to mitigate Wallerian degeneration. By promoting autonomous and selective alignment of nerve fiber gap sutures via structure design, the approach aims to achieve a harmonious unification of nerve regeneration, neuromotor function, and sensory recovery. It is anticipated that this groundbreaking technology will establish a robust platform for gene delivery in tissue engineering. [ABSTRACT FROM AUTHOR]

Background: Simulating the post-traumatic continuity defect of small human peripheral nerves, we compared the effectiveness of fibrin glue with neurorrhaphy for nerve gap restoration. Methods: In twenty-four male Wistar rats, a fifteen mm defect in one sciatic nerve only was made and immediately repaired with an inverted polarity autograft. According to the used technique, rats were divided into Group A (Control), using traditional neurorrhaphy, and Group B (Study), using fibrine glue sealing; in total, 50% of rats were sacrificed at 16 weeks and 50% at 21 weeks. Before sacrifice, an assessment of motor function was done through Walking Track Analysis and an electroneurophysiological evaluation. After sacrifice, selected muscle mass indexes and the histology of the regenerated nerves were assessed. All data were evaluated by Student's t test for unpaired data. Results: No significant differences were found between the two groups, with only the exception of a relative improvement in the tibialis anterior muscle's number of motor units in the study group. Conclusion: Despite the fact that the use of fibrin glue as a nerve sealant is not superior in terms of functional recovery, its effectiveness is comparable to that of microsurgical repair. Hence, the faster and technically easier glueing technique could deserve broader clinical application. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluates the impact of equol, a metabolite of soy isoflavone, on bladder dysfunction in rats with bladder outlet obstruction (BOO). In addition, we investigate its potential as a neuroprotective agent for the obstructed bladder and discuss its applicability in managing overactive bladder (OAB). Methods: Eighteen male Sprague–Dawley rats were divided into three groups (six rats per group) during the rearing period. The Sham and C‐BOO groups received an equol‐free diet, while the E‐BOO group received equol supplementation (0.25 g/kg). At 8 weeks old, rats underwent BOO surgery, followed by continuous cystometry after 4 weeks of rearing. The urinary oxidative stress markers (8‐hydroxy‐2′‐deoxyguanosine and malondialdehyde) were measured, and the bladder histology was analyzed using hematoxylin–eosin, Masson's trichrome, and immunohistochemical staining (neurofilament heavy chain for myelinated nerves, peripherin for unmyelinated nerves, and malondialdehyde). Results: Equol reduced BOO‐induced smooth muscle layer fibrosis, significantly prolonged the micturition interval (C‐BOO: 193 s, E‐BOO: 438 s) and increased the micturition volume (C‐BOO: 0.54 mL, E‐BOO: 1.02 mL) compared to the C‐BOO group. Equol inhibited the increase in urinary and bladder tissue malondialdehyde levels. While the C‐BOO group exhibited reduced peripherin alone positive nerve fibers within the smooth muscle layer, equol effectively attenuated this decline. Conclusions: Equol reduces lipid peroxidation and smooth muscle layer fibrosis in the bladder and exhibited neuroprotective effects on bladder nerves (peripheral nerves) and prevented the development of bladder dysfunction associated with BOO in rats. Consumption of equol is promising for the prevention of OAB associated with BOO. [ABSTRACT FROM AUTHOR]

Background: Parotidectomies are indicated for a variety of reasons. Regardless of the indication for surgery, facial reanimation may be required because of facial nerve sacrifice or iatrogenic damage. In these cases, facial restoration performed concurrently with ablative surgery is considered the gold standard, and delayed reanimation is usually not attempted. Methods: A retrospective review of all patients who underwent parotidectomies from 2009 to 2022 in a single institution was performed. Indications, surgical techniques, and outcomes of an algorithmic template were applied to these cases using the Sunnybrook, Terzis scores, and Smile Index. A comparison was made between immediate vs. late repairs. Results: Of a total of 90 patients who underwent parotidectomy, 17 (15.3%) had a radical parotidectomy, and 73 (84.7%) had a total or superficial parotidectomy. Among those who underwent complete removal of the gland and nerve sacrifice, eight patients (47.1%) had facial restoration. There were four patients each in the immediate (n = 4) and late repair (n = 4) groups. Surgical techniques ranged from cable grafts to vascularized cross facial nerve grafts (sural communicating nerve flap as per the Koshima procedure) and vascularized nerve flaps (chimeric vastus lateralis and anterolateral thigh flaps, and superficial circumflex perforator flap with lateral femoral cutaneous nerve). Conclusions: The algorithm between one technique and another should take into consideration age, comorbidities, soft tissue defects, presence of facial nerve branches for reinnervation, and donor site morbidity. While immediate facial nerve repair is ideal, there is still benefit in performing a delayed repair in this algorithm. [ABSTRACT FROM AUTHOR]

Severely damaged peripheral nerves will regenerate incompletely due to lack of directionality in their regeneration, leading to loss of nerve function. To address this problem, various nerve guidance conduits (NGCs) have been developed to provide guidance for nerve repair. However, their clinical application is still limited, mainly because its effect in promoting nerve repair is not as good as autologous nerve transplantation. Therefore, it is necessary to enhance the ability of NGCs to promote directional nerve growth. Strategies include preparing various directional structures on NGCs to provide contact guidance, and loading various substances on them to provide electrical stimulation or neurotrophic factor concentration gradient to provide directional physical or biological signals. [ABSTRACT FROM AUTHOR]

Objective: Common peroneal nerve (CPN) injury is a frequently encountered lower extremity injury. Furthermore, several previous studies have demonstrated that patients who underwent direct suturing of the CPN following rupture experienced unfavorable postoperative prognoses. Therefore, we aimed to present a novel modified surgical approach for CPN rupture and assess the effectiveness of this technique in restoring lower limb functionality. Methods: In this retrospective observational study, we included patients with CPN rupture who underwent one‐stage neurorrhaphy and posterior transposition combined with nerve wrapping using a gastrocnemius fascial flap for CPN rupture between January 2016 and December 2020. Lower limb function was evaluated using the lower extremity functional scale (LEFS) and British Medical Research Council (BMRC) grading system. We also assessed the influence of age, sex, duration of symptoms, mechanism of injury, and surgical modality on the postoperative recovery of lower extremity function using subgroup and regression analyses. Results: Thirty‐seven patients (mean age = 35.76 ± 13.01 years) with at least 2 years of follow‐up were included in the final analysis. The LEFS scores significantly improved after surgery at the last follow‐up (p < 0.01). Moreover, 67.57% of the patients achieved good or excellent postoperative outcomes (BMRC: M3 or above). Results of the subgroup analysis and regression models suggested that patients who underwent direct suturing showed better recovery of lower extremity function than those who underwent nerve grafting. Conclusion: One‐stage neurorrhaphy and posterior transposition combined with nerve wrapping using a gastrocnemius fascial flap exhibited encouraging outcomes in restoring lower‐limb function among patients with CPN rupture. This novel surgical technique is expected to be an effective method for treating CPN ruptures in the future. [ABSTRACT FROM AUTHOR]

Background: There are several methods developed for the treatment of high-level peripheral nerve injury (HLPNI) in the upper extremity. However, it causes significant loss of motor functions and sensory defects for the patients, and it is a challenging topic for surgeons. The purpose of our study is to analyze patient characteristics and long-term results of early and late repair of the HLPNI in the upper extremity. Patients and Methods: Patients who were operated from January 2016 to January 2022 due to HLPNI in the upper extremity are included. The characteristics of the patients, which are gender, age, affected nerve, time frame from the injury to operation time, mechanism of injury, whether nerve grafts are used during surgery, and mean follow-up time, are evaluated. Long-term functional results are assessed according to the British Medical Research Council scale during follow-up examinations. Results: The study included 24 patients, and the majority were male (79.1%). Sixteen patients were injured with sharp objects (66.6%). 41.6% of the patients are operated within 72 h after admission to the emergency room, whereas 58.4% of them are operated on after the outpatient clinic admission. The mean motor and sensory results of the patients who operated within the first 72 h after injury were M3S3+. The mean motor and sensory results of the patients who were operated on 72 h-1 month after the injury were M3S3, and for the patients who were operated on 1-5 months after the injury, the mean motor and sensory result was M2S2. The results of the injuries due to sharp objects were M3S3, whereas it was M2S2 for the patients who have been injured due to blunt trauma or firearms. Results of the patients under 20 years old were M3S3+; it was M3S2+ for the 20-50-year-old patients, whereas it was M2S2 for the patients older than 50 years old. Conclusion: Early repair is suggested for the HLPNI in the upper extremity, and gross motor function of the upper extremity is regained better, especially in young patients. Nerve graft necessity should be considered for the late repair. Early repair and secondary nerve repair with nerve graft are not always disappointing for the patient and the surgeon. [ABSTRACT FROM AUTHOR]

Purpose: In individuals who develop drop foot due to nerve loss, several methods such as foot-leg orthosis, tendon transfer, and nerve grafting are used. Nerve transfer, on the other hand, has been explored in recent years. The purpose of this study was to look at the tibial nerve's branching pattern and the features of its branches in order to determine the suitability of the tibial nerve motor branches, particularly the plantaris muscle motor nerve, for deep fibular nerve transfer. Methods: There were 36 fixed cadavers used. Tibial nerve motor branches were observed and measured, as were the lengths, distributions, and thicknesses of the common fibular nerve and its branches at the bifurcation region. Result: The motor branches of the tibial nerve that supply the soleus muscle, lateral head, and medial head of the gastrocnemius were studied, and three distinct forms of distribution were discovered. The motor branch of the gastrocnemius medial head was commonly observed as the first branch to divide, and it appeared as a single root. The nerve of the plantaris muscle was shown to be split from many origins. When the thickness and length of the motor branches measured were compared, the nerve of the soleus muscle was determined to be the most physically suited for neurotization. Conclusion: In today drop foot is very common. Traditional methods of treatment are insufficient. Nerve transfer is viewed as an application that can both improve patient outcomes and hasten the patient's return to society. The nerve of the soleus muscle was shown to be the best candidate for transfer in our investigation. [ABSTRACT FROM AUTHOR]