Exogenous GDNF promotes peripheral facial nerve regeneration in rats through the PI3K/AKT/mTOR signaling pathway.

Facial nerve regeneration still lacks a well-defined and practical clinical intervention. The survival of central facial motoneuron is a critical component in the successful peripheral facial nerve regeneration. Endogenous GDNF is vital for facial nerve regeneration according to earlier investigations. Nevertheless, the low endogenous GDNF level makes it challenging to achieve therapeutic benefits. Thus, we crushed the main trunk of facial nerve in SD rats to provide a model of peripheral facial paralysis, and we administered exogenous GDNF and Rapa treatments. We observed changes in the animal behavior scores, the morphology of facial nerve and buccinator muscle, the electrophysiological of facial nerve, and the expression of GDNF, GAP-43, and PI3K/AKT/mTOR signaling pathway-related molecules in the facial motoneurons. We discovered that GDNF could boost axon regeneration, hasten the recovery of facial paralysis symptoms and nerve conduction function, and increase the expression of GDNF, GAP-43, and PI3K/AKT/mTOR signaling pathway-related molecules in the central facial motoneurons. Therefore, exogenous GDNF injection into the buccinator muscle can enhance facial nerve regeneration following crushing injury and protect facial neurons via the PI3K/AKT/mTOR signaling pathway. This will offer a fresh perspective and theoretical foundation for the management of clinical facial nerve regeneration.

Porous Organic Materials in Tissue Engineering: Recent Advances and Applications for Severed Facial Nerve Injury Repair.

The prevalence of facial nerve injury is substantial, and the restoration of its structure and function remains a significant challenge. Autologous nerve transplantation is a common treatment for severed facial nerve injury; however, it has great limitations. Therefore, there is an urgent need for clinical repair methods that can rival it. Tissue engineering nerve conduits are usually composed of scaffolds, cells and neurofactors. Tissue engineering is regarded as a promising method for facial nerve regeneration. Among different factors, the porous nerve conduit made of organic materials, which has high porosity and biocompatibility, plays an indispensable role. This review introduces facial nerve injury and the existing treatment methods and discusses the necessity of the application of porous nerve conduit. We focus on the application of porous organic polymer materials from production technology and material classification and summarize the necessity and research progress of these in repairing severed facial nerve injury, which is relatively rare in the existing articles. This review provides a theoretical basis for further research into and clinical interventions on facial nerve injury and has certain guiding significance for the development of new materials.

The involvement of Neuregulin-1 in the process of facial nerve injury repair through the utilization of dental pulp stem cells.

BACKGROUND: Facial nerve injury often results in poor prognosis due to the challenging process of nerve regeneration. Neuregulin-1, a human calmodulin, is under investigation in this study for its impact on the reparative capabilities of Dental Pulp Stem Cells (DPSCs) in facial nerve injury. METHODS: Lentivirus was used to transfect and construct Neuregulin-1 overexpressed DPSCs. Various techniques assessed the effects of Neuregulin-1: osteogenic induction, lipid induction, Reverse Transcription Polymerase Chain Reaction, Western Blot, Cell Counting Kit-8 assay, wound healing, immunofluorescence, Phalloidin staining, nerve stem action potential, Hematoxylin-eosin staining, transmission electron microscopy, and immunohistochemistry. RESULTS: Neuregulin-1 effectively enhanced the proliferation, migration, and cytoskeletal rearrangement of DPSCs, while simultaneously suppressing the expression of Ras homolog gene family member A (RhoA) and Microfilament actin (F-actin). These changes facilitated the neural differentiation of DPSCs. Additionally, in vivo experiments showed that Neuregulin-1 expedited the restoration of action potential in the facial nerve trunk, increased the thickness of the myelin sheath, and stimulated axon regeneration. CONCLUSION: Neuregulin-1 has the capability to facilitate the repair of facial nerve injuries by promoting the regenerative capacity of DPSCs. Thus, Neuregulin-1 is a significant potential gene in the reparative processes of nerve damage.

Overexpression of c-Jun inhibits erastin-induced ferroptosis in Schwann cells and promotes repair of facial nerve function.

Myelin undergoes various changes after nerve injury, and c-Jun has a close relationship with Schwann cells (SCs). However, it remains unclear whether c-Jun can be involved in nerve repair by regulating ferroptosis. To explore this, we first set up a facial nerve injury model and detected the changes of ferroptosis-related proteins and c-Jun by immunofluorescence and Western blot. Then, we cultured RSC 96 and pSCs, and studied the potential regulatory relationships by a combination of experimental methods such as CCK-8, ELISA, immunofluorescence, qRT-PCR, Western blot and viral transfection. Finally, we corroborated the role of c-Jun through animal experiments. Our experiments revealed that ferroptosis occurs after facial nerve injury. Erastin decreased GPX4, c-Jun proteins and GSH content, while PTGS2, NRF2, HO-1 proteins, MDA, Fe2+ and ROS contents increased. This effect was inhibited after c-Jun overexpression but was reversed after the addition of c-Jun siRNA. Besides, we proved in vivo that c-Jun could inhibit ferroptosis and promote the recovery of facial nerve function. In conclusion, our study identified the relationship between c-Jun and ferroptosis during peripheral nerve injury repair, which provides new ideas for studying peripheral nerve injury and repair.

DHI Increases the Proliferation and Migration of Schwann Cells Through the PI3K/AKT Pathway and the Expression of CXCL12 and GDNF to Promote Facial Nerve Function Repair.

The facial nerve is one of the vulnerable nerves in otolaryngology. Repair and recovery of facial nerve injury have a high priority in clinical practice. The proliferation and migration of Schwann cells are considered of great significance in the process of nerve injury repair. Danhong injection (DHI), as a common drug for cardiovascular and cerebrovascular diseases, has been fully certified in neuroprotection research, but its role in facial nerve injury is still not clear. Our study found that DHI can promote the proliferation and migration of RSC96 cells, a Schwann cell line, and this effect is related to the activation of the PI3K/AKT pathway. LY294002, an inhibitor of PI3K, inhibits the proliferation and migration of RSC96 cells. Further studies have found that DHI can also promote the expression of CXCL12 and GDNF at gene and protein levels, and CXCL12 is, while GDNF is not, PI3K/AKT pathway-dependent. Animal experiments also confirmed that DHI could promote CXCL12 and GDNF expression and promote facial nerve function recovery and myelin regeneration. In conclusion, our in vitro and in vivo experiments demonstrated that DHI could promote the proliferation and migration of Schwann cells through the PI3K/AKT pathway and increase the expression of CXCL12 and GDNF to promote facial nerve function repair.

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway.

Many factors are involved in the process of nerve regeneration. Understanding the mechanisms regarding how these factors promote an efficient remyelination is crucial to deciphering the molecular and cellular processes required to promote nerve repair. Schwann cells (SCs) play a central role in the process of peripheral nerve repair/regeneration. Using a model of facial nerve crush injury and repair, we identified Annexin A1 (ANXA1) as the extracellular trigger of SC proliferation and migration. ANXA1 activated formyl peptide receptor 2 (FPR2) receptors and the downstream adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling cascade, leading to SC proliferation and migration in vitro. SCs lacking FPR2 or AMPK displayed a defect in proliferation and migration. After facial nerve injury (FNI), ANXA1 promoted the proliferation of SCs and nerve regeneration in vivo. Collectively, these data identified the ANXA1/FPR2/AMPK axis as an important pathway in SC proliferation and migration. ANXA1-induced remyelination and SC proliferation promotes FNI regeneration.

Efficacy of surgical repair for the functional restoration of injured facial nerve.

BACKGROUND: Early surgical repair to restore nerve integrity has become the most commonly practiced method for managing facial nerve injury. However, the evidence for the efficacy of surgical repair for restoring the function of facial nerves remains deficient. This study evaluated the outcomes of surgical repair for facial nerve lesions. METHODS: This retrospective observational study recruited 28 patients with the diagnosis of facial nerve injury who consecutively underwent surgical repairs from September 2012 to May 2019. All related clinical data were retrospectively analyzed according to age, sex, location of the facial nerve lesion, size of the facial nerve defect, method of repair, facial electromyogram, and blink reflex. Facial function was then stratified with the House-Brackmann grading system pre-operation and 3, 9, 15, and 21 months after surgical repair. RESULTS: The 28 patients enrolled in this study included 17 male and 11 female patients with an average age of 34.3 ± 17.4 years. Three methods were applied for the repair of an injured facial nerve, including great auricular nerve transplantation in 15 patients, sural nerve grafting in 7 patients, and hypoglossal to facial nerve anastomosis in 6 patients. Facial nerve function was significantly improved at 21 months after surgery compared with pre-operative function (P = 0.008). Following surgical repair, a correlation was found between the amplitude of motor unit potential (MUP) and facial nerve function (r = -6.078, P = 0.02). Moreover, the extent of functional restoration of the facial nerve at 21 months after surgery depended on the location of the facial nerve lesion; lesions at either the horizontal or vertical segment showed significant improvement(P = 0.008 and 0.005), while no functional restoration was found for lesions at the labyrinthine segment (P = 0.26). CONCLUSIONS: For surgical repair of facial nerve lesions, the sural nerve, great auricular nerve, and hypoglossal-facial nerve can be grafted effectively to store the function of a facial nerve, and MUP may provide an effective indicator for monitoring the recovery of the injured nerve.

Periangular transmasseteric infraparotid approach in the treatment of condylar-base and low condylar­neck fractures.

AIM: Mandibular condylar fractures account for 25 to 52 % of all mandibular fractures. Though current literature favors open reduction and internal fixation (ORIF) of condylar­base and low condylar­neck fractures, extraoral approaches are usually considered to be complicated by the risk of facial nerve injury and other possible complications. This study was undertaken to demonstrate that the periangular transmasseteric infraparotid surgical approach (TMIP) to condylar­base and low condylar­neck fractures provides excellent access to the bony fragments with minimal risk of complications such as facial nerve and parotid gland injury. PATIENTS: In the period from January 2010 to December 2018, 81patients (96 fractures) with condylar­base and low condylar­neck fractures underwent ORIF via periangular transmasseteric infraparotid surgical approach. RESULTS: The results of this retrospective study showed minimal postoperative complications. The periangular transmasseteric infraparotid surgical approach allowed precise anatomic repositioning and fixation of the bony fragments in almost all cases except for two juvenile cases with noticeable scars and one case with plate fracture. There were no transient or permanent facial nerve palsies, parotid gland or salivary fistulae complications during a 12­month follow­up period. CONCLUSION: The periangular infraparotid transmasseteric approach to ORIF of condylar­base and low condylar­neck fractures is an effective and safe approach allowing accurate anatomic reposition and fixation of the fragments with minimum surgical complications (Tab. 1, Fig. 12, Ref. 21).

Overexpression of Foxc1 regenerates crushed rat facial nerves by promoting Schwann cells migration via the Wnt/ß-catenin signaling pathway.

Facial paralysis can result in severe implications for patients. A good prognosis depends on the degree of nerve regeneration. Schwann cells (SCs) play an important role in facial nerve development and regeneration through migration. Forkhead box C1 (Foxc1), a member of the forkhead transcription factor family, is implicated in cell migration. However, the role of Foxc1 in the progression after facial nerve crush remains unknown. Our aim was to evaluate the effect of Foxc1 overexpression on SC migration and recovery of facial nerves after crush injury. The rat facial nerve crush injury model was established through the use of unilateral surgery. The results showed that the expression of Foxc1 was increased in the surgery group compared to that of the control group. SCs were isolated from the sciatic nerves and cultured. Foxc1, delivered by an adeno-associated virus in vivo, or adenovirus in vitro, both induced overexpression of Foxc1, and increased the expression of CXCL12 and ß-catenin. After the transfection of Foxc1, the migration of SC was increased both in vitro and in vivo, was reduced by the inhibition of CXCL12 or ß-catenin. The facial nerve function and the nerve axon remyelination of the rats transfected with Foxc1 were significantly improved after nerve crush injury. Overall, the results demonstrated that overexpression of Foxc1 promoted SC migration by regulating CXCL12 via the Wnt/ß-catenin pathway, thus contributing to improved facial nerve function after crush injury.

Two Pathways Regulate Differential Expression of nAChRs Between the Orbicularis Oris and Gastrocnemius.

BACKGROUND: We previously demonstrated differential expression of nicotinic acetylcholine receptors (nAChRs) in the facial nerve-innervated orbicularis oris and somatic nerve-innervated gastrocnemius, which contribute to different sensitivities to muscle relaxants. Furthermore, the orbicularis oris exhibits less sensitivity to muscle relaxants after facial nerve injury, which is also related to upregulation of nAChRs. Here, we explored the regulatory mechanism for the different expression patterns. Because the agrin/Lrp4/MuSK/rapsyn and neuregulin1/ErbB signaling pathways are indispensable for maintaining the expression of nAChRs, we examined the activity of these two signaling pathways in gastrocnemius and orbicularis oris innervated by normal or injured facial nerves. MATERIALS AND METHODS: A quantitative analysis of these two signaling pathways was realized by immunofluorescence, and immunoprecipitation was applied to detect the level of phosphorylated MuSK in the gastrocnemius and orbicularis oris innervated by normal or injured facial nerves in adult rats. RESULTS: ErbB and the phosphorylated MuSK were expressed more in orbicularis oris than in gastrocnemius (P < 0.05). No significant difference was found in the expression of agrin/Lrp4/MuSK/rapsyn. After facial nerve injury, the level of agrin and the percentage of phosphorylated MuSK decreased significantly, although the expression levels of MuSK, rapsyn, and neuregulin1/ErbB were highly upregulated. CONCLUSIONS: Differential expression of the neuregulin1/ErbB signaling pathway may account for the different expression patterns of nAChRs at the neuromuscular junctions of the orbicularis oris and gastrocnemius. Overexpression of MuSK and rapsyn may contribute to upregulation of nAChRs after facial nerve injury.

[Facial nerve injury in neurosurgery: a rehabilitation potential of botulinum therapy]. / Porazhenie litsevogo nerva pri neirokhirurgicheskikh operatsiiakh: reabilitatsionnyi potentsial botulinoterapii.

Surgical treatment of posterior cranial fossa and cerebellopontine angle tumors is associated with a risk of facial nerve dysfunction. The causes for facial muscle paresis include nerve compression by the tumor, destruction of the nerve structure by the tumor growing from nerve fibers, nerve injury during surgical removal of the tumor, etc. The first 3 months after facial nerve injury are a potential therapeutic window for the use of botulinum toxin type A (BTA). During this period, the drug is introduced both in the healthy side to improve the facial symmetry at rest and during mimetic movements and in the affected side to induce drug-induced ptosis. Post-paralytic syndrome develops 4-6 months after facial nerve injury. At this stage, administration of BTA is also an effective procedure; in this case, drug injections are performed on the affected side at small doses and symmetrically on the healthy side at doses doubling those for the affected side. BTA injections are mandatory in complex treatment of facial muscle paralysis.

Nicotine effects on muscarinic receptor-mediated free Ca[Formula: see text] level changes in the facial nucleus following facial nerve injury.

It was suggested that muscarinic, and nicotinic receptors increase free Ca[Formula: see text] levels in the facial nerve nucleus via various channels following facial nerve injury. However, intracellular Ca[Formula: see text] overload can trigger either necrotic or apoptotic cell death. It is assumed that, following facial nerve injury, the interactions of nicotinic and muscarinic acetylcholine receptors in facial nerve nucleus may negatively regulate free Ca[Formula: see text] concentrations in the facial nerve nucleus, which provide important information for the repair and regeneration of the facial nerve. The present study investigated the regulatory effects of nicotine on muscarinic receptor-mediated free calcium ion level changes in the facial nucleus in a rat model of facial nerve injury at 7, 30, and 90 days following facial nerve injury using laser confocal microscopy. The dose-dependent regulation of nicotine on muscarinic receptor-mediated free calcium ion level changes in the facial nucleus may decrease the range of free Ca[Formula: see text] increases following facial nerve injury, which is important for nerve cell regeneration. It is concluded that the negative effects of nicotine on muscarinic receptors are related to the [Formula: see text] subtype of nicotinic receptors.

Synaptic plasticity in the facial nucleus in rats following infraorbital nerve manipulation after facial nerve injury.

The aim of this study is to investigate the effect of sensory input on the neural plasticity in the facial nucleus following facial nerve injury. Adult male Wistar rats were randomly assigned to four groups: (1) sham control; (2) facial nerve crush (FNC); (3) nerve crush plus daily manual vibrissal stimulation (FMS); and (4) nerve crush with infraorbital nerve transection plus daily manual stimulation (FIMS). Plasticity related proteins in the facial nucleus were evaluated by western blot at 7, 14, and 28 days postsurgery (n = 6/group per timepoint). Synaptophysin-positive terminals were evaluated by immunohistochemistry in a second set of animals (n = 6/group) at 14 days. Quantitation of synaptophysin immunostaining showed that rats in the FNC group had a significantly lower mean number of pixels compared to control animals (29.1 ± 2.6 × 10(6) vs. 34.2 ± 2.3 × 10(6); P < 0.05). Values in the FMS group (33.2 ± 1.7 × 10(6)) were similar to that of the control group, while the mean number in the FIMS group (26.5 ± 2.4 × 10(6)) was significantly lower than in the control group. Synapsin I phosphorylation was reduced to 70-83 % in FNC rats, but increased to 121-132 % in the FMS group (P < 0.05 vs. controls). Phosphorylation of cAMP response element-binding protein was similarly reduced by facial nerve crush, which was delayed in FMS animals (P < 0.05 vs. controls at 28 days). Expression and phosphorylation of all proteins were reduced to the lowest in the FIMS group (all P < 0.05). Sensory input from the IoN have a strong effect on synaptic plasticity within the facial nucleus, which is necessary to achieve the benefit of manual stimulation.

Results of anterior facial nerve rerouting procedures for removing skull base tumors.

OBJECTIVES: The purpose of this study was to estimate the rates of functional recovery of the facial nerve and of total tumor resection in patients who undergo short anterior rerouting and long anterior rerouting of the facial nerve in removal of skull base tumors. METHODS: We retrospectively collected data on 37 patients with skull base tumors who underwent facial nerve rerouting during the procedure for tumor removal. Information on the rerouting technique, the completeness of tumor resection, and changes in facial nerve function were obtained from the medical records. Rerouting techniques were classified as short anterior rerouting or long anterior rerouting. RESULTS: Ten of 16 patients (62.5%) in the group with short anterior rerouting showed postoperative facial palsy, and all completely recovered within 1 year. In the group with long anterior rerouting, 18 of 21 patients (85.7%) showed postoperative facial palsy, and recovery to a preoperative level of facial function was found in 10 patients at 1 year of follow-up. Total tumor resection was possible in 94% and 81% of patients with short rerouting and long rerouting, respectively. The mean operation time was not significantly related to the postoperative recovery of facial function. CONCLUSIONS: Short rerouting techniques, when appropriately chosen on the basis of tumor and patient characteristics, offer excellent preservation of facial function and tumor resection, comparable to those of long rerouting techniques.

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

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

Electrophysiological and histopathological evaluation of the effectiveness of melatonin and glatiramer acetate for traumatic facial nerve injuries.

AIM: This study aimed to evaluate the effect of systemic/local use of melatonin and glatiramer acetate on regeneration in traumatic nerve injury models. MATERIALS AND METHODS: A total of 42 male Wistar albino rats were randomly divided into 6 groups: healthy control (Group 1), injured control (Group 2), local melatonin (Group 3), systemic melatonin (Group 4), local glatiramer acetate (Group 5), and systemic glatiramer acetate (Group 6). In all groups, electromyography recordings of the facial nerve were obtained after surgery and before sacrifice, and the damaged nerve region was histopathologically examined after sacrifice. RESULTS: In the electrophysiological evaluation, the control group had the greatest decrease in amplitude and extension in latency time following surgery than the treatment groups. Furthermore, a significant decrease in the degenerative axon count, edematous areas, and fibrotic areas as well as a significant increase in axonal surface areas was observed in all the treatment groups compared with the damage control group. CONCLUSIONS: Although both glatiramer acetate and melatonin are beneficial in regeneration in traumatic facial nerve injuries, it can be concluded that systemic use of melatonin can yield more positive results than glatiramer acetate and local use of both two drugs.

Evolution of Superficial Muscular Aponeurotic System Facelift Techniques: A Comprehensive Systematic Review of Complications and Outcomes.

Background: Facelift procedures are a popular method of facial rejuvenation. The most common technique is superficial muscular aponeurotic system (SMAS) plication, with several variations. However, the optimal approach remains unclear. This review analyzed previous studies to compare SMAS facelift techniques, their outcomes, and complication rates. Methods: A systematic search was conducted using the MEDLINE, Cochrane, Embase, and Google Scholar electronic databases in September 2022. The search included studies published from January 2000 to September 2022 using keywords such as "facelift," "complications," and "outcomes." Results: This review examined 27 selected studies that evaluated 6 SMAS facelift techniques. The studies involved 6086 patients in total, over 85% of who were satisfied with the outcome of their surgery. The complication rates varied depending on the technique used, with the SMAS flap and composite SMAS technique having the highest (5.75%) and lowest (0.05%) complication rates, respectively. The most common complications were temporary facial nerve injury (0.85%) and skin necrosis (0.41%). To date, only one case of permanent facial nerve injury has been reported. Conclusions: On the basis of our findings, SMAS facelift techniques achieve high patient satisfaction rates, with complication rates that vary by technique. The composite SMAS technique showed the lowest complication rates, whereas the SMAS flap showed the highest rate. However, some studies have not reported all complications, making it difficult to determine the best approach. Therefore, future studies are required to identify the most aesthetically pleasing technique with the lowest complication risk.

Incidence of Facial Nerve Injury and Sialocele Formation Following Mandibular Condylar and Sub-condylar Fracture Fixation.

Purpose: To study the incidence of sialocele formation in the parotid gland and to study the incidence of facial nerve affliction following treatment of mandibular condylar and sub-condylar fractures. Materials and methods: The present study is a retrospective study conducted on a total of 82 patients with 107 sub-condylar and condylar fractures treated in this centre from August 2008 to August 2020. The surgical approaches used to treat the fractures were considered, and the occurrence of sialocele, salivary fistula and facial nerve paralysis was noted. The facial nerve function was analysed using House-Brackmann system of classification. Results: The incidence of sialocele formation was seen in 15.87% of cases, and the incidence was seen more commonly during a preauricular approach (52.94%) followed by retromandibular (41.17%) followed by anterior parotid transmassetric approach (11.76%). The incidence of facial nerve affliction was seen in 17.57% of cases with majority of them showing temporal branch involvement in 21.05% of cases. Conclusion: During the treatment of condylar and sub-condylar fractures, the facial nerve is at considerable risk of damage; however, understanding the anatomy of the nerve is of importance to avoid such complications. Sialocele formation is also an undesirable complication of such surgeries, a prompt diagnosis and early treatment is mandatory to overcome further unwanted sequel.

Hypoxic Bone Mesenchymal Stem Cell-Derived Exosomes Direct Schwann Cells Proliferation, Migration, and Paracrine to Accelerate Facial Nerve Regeneration via circRNA_Nkd2/miR-214-3p/MED19 Axis.

Background: Facial nerves have the potential for regeneration following injury, but this process is often challenging and slow. Schwann cells (SCs) are pivotal in this process. Bone mesenchymal stem cells (BMSC)-derived exosomes promote tissue repair through paracrine action, with hypoxic preconditioning enhancing their effects. The main purpose of this study was to determine whether hypoxia-preconditioned BMSC-derived exosomes (Hypo-Exos) exhibit a greater therapeutic effect on facial nerve repair/regeneration and reveal the mechanism. Methods: CCK-8, EdU, Transwell, and ELISA assays were used to evaluate the functions of Hypo-Exos in SCs. Histological analysis and Vibrissae Movements (VMs) recovery were used to evaluate the therapeutic effects of Hypo-Exos in rat model. circRNA array was used to identify the significantly differentially expressed exosomal circRNAs between normoxia-preconditioned BMSC-derived exosomes (Nor-Exos) and Hypo-Exos. miRDB, TargetScan, double luciferase assay, qRT-PCR and WB were used to predict and identify potential exosomal cirRNA_Nkd2-complementary miRNAs and its target gene. The function of exosomal circRNA_Nkd2 in facial nerve repair/regeneration was evaluated by cell and animal experiments. Results: This study confirmed that Hypo-Exos more effectively promote SCs proliferation, migration, and paracrine function, accelerating facial nerve repair following facial nerve injury (FNI) compared with Nor-Exos. Furthermore, circRNA analysis identified significant enrichment of circRNA_Nkd2 in Hypo-Exos compared with Nor-Exos. Exosomal circRNA_Nkd2 positively regulates mediator complex subunit 19 (MED19) expression by sponging rno-miR-214-3p. Conclusion: Our results demonstrated a mechanism by which Hypo-Exos enhanced SCs proliferation, migration, and paracrine function and facial nerve repair and regeneration following FNI through the circRNA_Nkd2/miR-214-3p/Med19 axis. Hypoxic preconditioning is an effective and promising method for optimizing the therapeutic action of BMSC-derived exosomes in FNI.

Risk factors for postoperative facial nerve injury in retromandibular-approach surgery: A retrospective study including CT measurements of maxillofacial bone structure.

The purpose of this retrospective study was to identify risks of postoperative facial nerve injury (FNI) in mandibular condylar fractures. A total of 59 consecutive cases of condyle fracture or plate removal with a retromandibular transparotid approach (RMTA) were divided into FNI and non-FNI groups that were evaluated for associations with age, sex, laterality, fracture type, height, weight, body mass index (BMI), and maxillofacial bone height and width diameters on computed tomography (CT). FNI occurred in 11 of 59 patients (18.64%), all of them female (p = 0.0011). Other statistically significant factors on univariate analysis for FNI included a short height (156.95 ± 8.16 cm vs. 164.29 ± 9.89 cm, p = 0.04), low weight (46.08 ± 8.03 kg vs. 58.94 ± 11.79 kg, p = 0.003), low BMI (18.64 ± 2.63 kg/m2 21.68 ± 3.02 kg/m2, p = 0.007), short condylion-anterior fracture distance (19.34 ± 3.15 mm vs. 22.26 ± 3.96 mm, p = 0.04) and short condylion-posterior fracture distance (20.12 ± 3.98 mm vs. 25.45 ± 5.02 mm, p = 0.009). Our retrospective study suggested that FNI with RMTA surgery occurs particularly in female patients and may occur more frequently in patients who are short, lean or have high condyle fractures.