GFP-labeled Schwann cell-like cells derived from hair follicle epidermal neural crest stem cells promote the acellular nerve allografts to repair facial nerve defects in rats.

BACKGROUND: Acellular nerve allografts (ANAs) have been successfully applied to bridge facial nerve defects, and transplantation of stem cells may enhance the regenerative results. Up to now, application of hair follicle epidermal neural crest stem cell-derived Schwann cell-like cells (EPI-NCSC-SCLCs) combined with ANAs for bridging facial nerve defects has not been reported. METHODS: The effect of ANAs laden with green fluorescent protein (GFP)-labeled EPI-NCSC-SCLCs (ANA + cells) on bridging rat facial nerve trunk defects (5-mm-long) was detected by functional and morphological examination, as compared with autografts and ANAs, respectively. RESULTS: (1) EPI-NCSC-SCLCs had good compatibility with ANAs in vitro. (2) In the ANA + cells group, the GFP signals were observed by in vivo imaging system for small animals within 8 weeks, and GFP-labeled EPI-NCSC-SCLCs were detected in the tissue slices at 16 weeks postoperatively. (3) The facial symmetry at rest after surgery in the ANA + cells group was better than that in the ANA group (p < 0.05), and similar to that in the autograft group (p > 0.05). The initial recovery time of vibrissal and eyelid movement in the ANA group was 2 weeks later than that in the other two groups. (4) The myelinated fibers, myelin sheath thickness and diameter of the axons of the buccal branches in the ANA group were significantly worse than those in the other two groups (P < 0.05), and the results in the ANA + cells group were similar to those in the autograft group (p > 0.05). CONCLUSIONS: EPI-NCSC-SCLCs could promote functional and morphological recovery of rat facial nerve defects, and GFP labeling could track the transplanted EPI-NCSC-SCLCs in vivo for a certain period of time. These may provide a novel choice for clinical treatment of peripheral nerve defects.

Facial nerve regeneration via body-brain crosstalk: The role of stem cells and biomaterials.

The human body is a complex, integral whole, and disruptions in one organ can lead to dysfunctions in other parts of the organ network. The facial nerve, as the seventh cranial nerve, arises from the brainstem, controls facial expression muscles and plays a crucial role in brain-body communication. This vulnerable nerve can be damaged by trauma, inflammation, tumors, and congenital diseases, often impairing facial expression. Stem cells have gained significant attention for repairing peripheral nerve injuries due to their multidirectional differentiation potential. Additionally, various biomaterials have been used in tissue engineering for regeneration and repair. However, the therapeutic potential of stem cells and biomaterials in treating facial nerve injuries requires further exploration. In this review, we summarize the roles of stem cells and biomaterials in the regeneration and repair of damaged facial nerves, providing a theoretical basis for the recovery and reconstruction of body-brain crosstalk between the brain and facial expression muscles.

Enhancing nerve regeneration in infraorbital nerve injury rat model: effects of vitamin B complex and photobiomodulation.

Orofacial nerve injuries may result in temporary or long-term loss of sensory function and decreased quality of life in patients. B vitamins are required for DNA synthesis and the repair and maintenance of phospholipids. In particular, vitamins B1, B6, and B12 are essential for neuronal function. Deficiency in vitamin B complex (VBC) has been linked to increased oxidative stress, inflammation and demyelination. Photobiomodulation (PBM) has antioxidant activity and is neuroprotective. In addition, a growing literature attests to the positive effects of PBM on nerve repair. To assess the effect of PBM and VBC on regenerative process we evaluated the expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), myelin basic protein (MBP), laminin and neurofilaments (NFs) using Western blotting to identify regenerative pattern after chronic constriction injury of the infraorbital nerve (CCI IoN) treated by PBM, VBC or its combination. After CCI IoN, the rats were divided into six groups naive, sham, injured (CCI IoN), treated with photobiomodulation (904 nm, 6.23 J/cm2, CCI IoN + PBM), treated with VBC (containing B1, B6 and B12) 5 times, CCI IoN + VBC) and treated with PBM and VBC (CCI IoN + VBC + PBM). The treatments could revert low expression of BDNF, MBP and laminin. Also reverted the higher expression of neurofilaments and enhanced expression of NGF. PBM and VBC could accelerate injured infraorbital nerve repair in rats through reducing the expression of neurofilaments, increasing the expression of BDNF, laminin and MBP and overexpressing NGF. These data support the notion that the use of PBM and VBC may help in the treatment of nerve injuries. This finding has potential clinical applications.

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 SELENOT mimetic PSELT promotes nerve regeneration by increasing axonal myelination in a facial nerve injury model in female rats.

Peripheral nerve injury (PNI) is frequent and many patients suffer lifelong disabilities in severe cases. Although the peripheral nervous system is able to regenerate, its potential is limited. In this study, we tested in a nerve regeneration model in rat the potential beneficial effect of a short mimetic peptide, named PSELT, which derives from SELENOT, an essential thioredoxin-like selenoprotein endowed with neuroprotective and antioxidant activities. For this purpose, the right facial nerve of female Long-Evans rats was axotomized then bridged with a free femoral vein interposition graft. PSELT (1 µM) was injected into the vein immediately and 48 h after the injury, and the effects observed were compared to those found after an end-to-end suture used as a gold standard treatment. Whisking behavior, electrophysiological potential, and histological analyses were performed 3 months after injury to determine the effects of these treatments. These analyses revealed that PSELT-treated animals exhibit a better motor recovery in terms of protraction amplitude and velocity of vibrissae compared to control and end-sutured nerve animal groups. Moreover, administration of PSELT following injury enhanced muscle innervation, axonal elongation, and myelination of newly formed nerve fibers. Altogether, these results indicate that a PSELT-based treatment is sufficient to enhance facial nerve myelination and regeneration and could represent a new therapeutic tool to treat PNI.

Potential Therapeutic Strategies and Substances for Facial Nerve Regeneration Based on Preclinical Studies.

Despite advances in microsurgical technology and an improved understanding of nerve regeneration, obtaining satisfactory results after facial nerve injury remains a difficult clinical problem. Among existing peripheral nerve regeneration studies, relatively few have focused on the facial nerve, particularly how experimental studies of the facial nerve using animal models play an essential role in understanding functional outcomes and how such studies can lead to improved axon regeneration after nerve injury. The purpose of this article is to review current perspectives on strategies for applying potential therapeutic methods for facial nerve regeneration. To this end, we searched Embase, PubMed, and the Cochrane library using keywords, and after applying exclusion criteria, obtained a total of 31 qualifying experimental studies. We then summarize the fundamental experimental studies on facial nerve regeneration, highlighting recent bioengineering studies employing various strategies for supporting facial nerve regeneration, including nerve conduits with stem cells, neurotrophic factors, and/or other therapeutics. Our summary of the methods and results of these previous reports reveal a common feature among studies, showing that various neurotrophic factors arising from injured nerves contribute to a microenvironment that plays an important role in functional recovery. In most cases, histological examinations showed that this microenvironmental influence increased axonal diameter as well as myelination thickness. Such an analysis of available research on facial nerve injury and regeneration represents the first step toward future therapeutic strategies.

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.

Early and continued manual stimulation is required for long-term recovery after facial nerve injury.

INTRODUCTION: We previously have shown that manual stimulation (MS) of vibrissal muscles for 2 months after facial nerve injury in rats improves whisking and reduces motor end plate polyinnervation. Here, we seek to determine whether discontinuing or delaying MS after facial-facial anastomosis (FFA) leads to similar results. METHODS: Rats were subjected to FFA and received MS for (1) 4 months (early and continued), (2) the first but not the last 2 months (discontinued), or (3) the last 2 months (delayed). Intact animals and those not receiving MS (no MS) were also examined. RESULTS: Early and continued MS restored whisking amplitude to 43°, a value significantly higher compared with the discontinued, delayed, and no MS groups (32°, 24°, and 10°, respectively). Motor end plate polyinnervation occurred in all experimental groups but was significantly higher in the delayed group. DISCUSSION: Early and continued MS results in better recovery than when it is either discontinued or delayed. Muscle Nerve 57: 100-106, 2018.

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.

Intracranial supramaximal facial nerve stimulation: a murine model.

PURPOSE: Supramaximal facial nerve stimulation is an applied current sufficient to evoke a maximal electromyographic response of facial musculature. It is used during cerebellopontine angle surgery for prognostication of postoperative nerve function. We utilized a rat model to examine safe parameters for intracranial electrical stimulation. MATERIALS AND METHODS: Intracranial facial nerve stimulation with electromyographic monitoring of 14 rats was performed. Supramaximal current level was determined and 50 additional pulses of supramaximal (4 rats), 3 times supramaximal (4), 10 times supramaximal (3), or zero (3) current were applied. To monitor progression of facial nerve injury, video recordings of vibrissae movements and eye closure were captured at 1, 3 and 28 days after surgery; animals were sacrificed on day 28, when nerve morphometry was performed. RESULTS: One rat in the supramaximal stimulation group (of 4), and one rat in the 10 times supramaximal stimulation group (of 3) demonstrated persistent impairment of facial nerve function as evidenced by decreased amplitude of vibrissae sweeping and eye closure impairment. The remainder of rats in all experimental groups demonstrated symmetric and normal facial nerve function at all time points. CONCLUSIONS: A novel animal model for supramaximal stimulation of the rat intracranial facial nerve is described. A small proportion of animals demonstrated functional evidence of nerve injury postoperatively. Function was preserved in some animals after stimulation with current order of magnitude higher than supramaximal levels. Further study with this model is necessary to definitively isolate the effects of surgical trauma from those of supramaximal electrical stimulation.

Mesenchymal Stem Cell-Derived Exosomes Promote Recovery of The Facial Nerve Injury through Regulating Macrophage M1 and M2 Polarization by Targeting the P38 MAPK/NF-Κb Pathway.

Facial nerve (FN) injury seriously affects human social viability and causes a heavy economic and social burden. Although mesenchymal stem cell-derived exosomes (MSC-Exos) promise therapeutic benefits for injury repair, there has been no evaluation of the impact of MSC-Exos administration on FN repair. Herein, we explore the function of MSC-Exos in the immunomodulation of macrophages and their effects in repairing FN injury. An ultracentrifugation technique was used to separate exosomes from the MSC supernatant. Administrating MSC-Exos to SD rats via local injection after FN injury promoted axon regeneration and myelination and alleviated local and systemic inflammation. MSC-Exos facilitated M2 polarization and reduced the M1-M2 polarization ratio. miRNA sequencing of MSC-Exos and previous literature showed that the MAPK/NF-κb pathway was a downstream target of macrophage polarization. We confirmed this hypothesis both in vivo and in vitro. Our findings show that MSC-Exos are a potential candidate for treating FN injury because they may have superior benefits for FN injury recovery and can decrease inflammation by controlling the heterogeneity of macrophages, which is regulated by the p38 MAPK/NF-κb pathway.

Predicting in vivo therapeutic efficacy of CelTrac1000-labeled hair follicle epidermal neural crest stem cells in models of repairing rat facial nerve defects via second near-infrared fluorescence imaging.

AIMS: To detect the therapeutic efficacy of CelTrac1000-labeled hair follicle epidermal neural crest stem cells (EPI-NCSCs) on repairing facial nerve defects by second near-infrared (NIR-II) fluorescence imaging. MATERIALS AND METHODS: Firstly, CelTrac1000-labeled EPI-NCSCs were microinjected into the acellular nerve allografts (ANAs) to bridge a 10-mm-long gap in the buccal branch of facial nerve in adult rats. Then, Celtrac1000-labeled EPI-NCSCs were detected by NIR-II fluorescence imaging system to visualize the behavior of the transplanted cells in vivo. Additionally, the effect of the transplanted EPI-NCSCs on repairing facial nerve defect was examined. KEY FINDINGS: Through 14 weeks of dynamic observation, the transplanted EPI-NCSCs survived in the ANAs in vivo after surgery. Meanwhile, the region of the NIR-II fluorescence signals was gradually limited to be consistent with the direction of the regenerative nerve segment. Furthermore, the results of functional and morphological analysis showed that the transplanted EPI-NCSCs could promote the recovery of facial paralysis and neural regeneration after injury. SIGNIFICANCE: Our research provides a novel way to track the transplanted cells in preclinical studies of cell therapy for facial paralysis, and demonstrates the therapeutic potential of EPI-NCSCs combined with ANAs in bridging rat facial nerve defects.

Management of facial nerve trauma.

PURPOSE OF REVIEW: To present the current literature on management of facial nerve disorder secondary to trauma, with a focus on the utility of electrodiagnostic testing in this setting. RECENT FINDINGS: Patients with facial palsy related to temporal bone fractures should be started on high-dose corticosteroids as early as possible. Recent literature on the benefit of surgical intervention in the setting of temporal bone fracture is mixed. Some studies support early surgical decompression whereas others have found no benefit compared with conservative treatment. SUMMARY: The management of facial nerve trauma is based on location and extent of injury. Extratemporal trauma and transected nerve should be treated with surgical exploration and tension-free coaptation ideally within 72 h. There are no guidelines for intratemporal facial nerve trauma. Surgical decompression compared with medical management is debated in the literature without consensus and more large studies are needed.

[Diagnosis and treatment of 68 cases of traumatic facial nerve paralysis].

Objective:To summarize the clinical characteristics and therapeutic effect of traumatic facial nerve palsy. Methods:Sixty-eight cases of traumatic facial nerve palsy were retrospectively analyzed from January 2015 to May 2023. Results:The median course of disease was 33 days. The facial nerve function of the patients was grade HB-Ⅱin 2 cases, grade HB-Ⅲ in 4 cases, grade HB-Ⅳin 16 cases, grade HB-Ⅴ in 37 cases（38 ears）, and grade HB-Ⅵ in 9 cases. 42 cases occurred immediately after injury and 26 cases were delayed. CT examination of temporal bone revealed longitudinal fractures in 51 cases（52 ears） , transverse fractures in 6 cases and mixed fractures in 4 cases. No definite temporal bone fracture was found in the remaining 7 cases. The segments of facial nerve injury in 49 cases（50 ears） were geniculate ganglion and adjacent, in 7 cases were vertical segment, in 7 cases were horizontal segment, in 2 cases were horizontal segment and vertical segment; and the other 3 cases could not be evaluated. Conservative treatment with glucocorticoids was used in 23 ears and surgery was used in 46 ears. Patients were followed up 6-24 months after treatment, including 20 cases of grade HB-Ⅰ, 19 cases of grade HB-Ⅱ, 23 cases（24 ears） of grade HB-Ⅲ, 4 cases of grade HB-Ⅳ, and 1 case of grade HB-Ⅴ.One patient was lost to follow-up. After treatment, the facial nerve function of patients was significantly improved（P<0.05）, and there were significant differences between conservative treatment group and surgical treatment group in the course of facial nerve palsy, the ratio of facial palsy immediately after injury, the nerve function before treatment and the nerve function after treatment（P<0.05）. There were no significant differences in age, sex, hearing condition, temporal bone fracture, facial nerve injury segment and rate of favorable neurologic outcomes（P>0.05）. The comparison of patients with neurodegeneration rate>90% and ≤90% showed that the facial nerve function of patients with neurodegeneration rate>90% before treatment was significantly worse（P<0.05）, but there was no significant difference between the facial nerve function after treatment（P>0.05）. There was no significant difference in facial nerve function between middle fossa approach group and mastoid approach group（P>0.05）. Conclusion:Patients with traumatic facial nerve palsy should be evaluated individually. Patients with mild facial nerve palsy, low neurodegeneration rate and short course of disease can be treated conservatively and followed up closely. Patients with severe facial nerve palsy, high neurodegeneration rate and more than 6 weeks of disease can be actively considered surgery. Good prognosis can be obtained by correct evaluation and treatment.

Enhancing facial nerve regeneration with scaffold-free conduits engineered using dental pulp stem cells and their endogenous, aligned extracellular matrix.

Objective. Engineered nerve conduits must simultaneously enhance axon regeneration and orient axon extension to effectively restore function of severely injured peripheral nerves. The dental pulp contains a population of stem/progenitor cells that endogenously express neurotrophic factors (NTFs), growth factors known to induce axon repair. We have previously generated scaffold-free dental pulp stem/progenitor cell (DPSC) sheets comprising an aligned extracellular matrix (ECM). Through the intrinsic NTF expression of DPSCs and the topography of the aligned ECM, these sheets both induce and guide axon regeneration. Here, the capacity of bioactive conduits generated using these aligned DPSC sheets to restore function in critical-sized nerve injuries in rodents was evaluated.Approach. Scaffold-free nerve conduits were formed by culturing DPSCs on a substrate with aligned microgrooves, inducing the cells to align and deposit an aligned ECM. The sheets were then detached from the substrate and assembled into scaffold-free cylindrical tissues.Main results. In vitroanalyses confirmed that scaffold-free DPSC conduits maintained an aligned ECM and had uniformly distributed NTF expression. Implanting the aligned DPSC conduits across critical-sized defects in the buccal branch of rat facial nerves resulted in the regeneration of a fascicular nerve-like structure and myelinated axon extension across the injury site. Furthermore, compound muscle action potential and stimulated whisker movement measurements revealed that the DPSC conduit treatment promoted similar functional recovery compared to the clinical standard of care, autografts. Significance. This study demonstrates that scaffold-free aligned DPSC conduits supply trophic and guidance cues, key design elements needed to successfully promote and orient axon regeneration. Consequently, these conduits restore function in nerve injuries to similar levels as autograft treatments. These conduits offer a novel bioactive approach to nerve repair capable of improving clinical outcomes and patient quality of life.

Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/mTOR Signaling Pathway.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS: EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.

Elevated TRPV2 expression in the facial nerve of rats by cold stimulation: Implications for Bell's palsy.

OBJECTIVE: Bell's palsy, also referred to as clinical manifestations of unilateral facial nerve palsy, encompasses downward angling of the corners of the mouth, the absence of forehead creases, and unilateral incomplete eyelid closure. The incidence of Bell's palsy has increased progressively in recent years, but the underlying mechanism of its occurrence remains unknown; therefore, it is essential to investigate both the cause and treatment of Bell's palsy. Member 2 of the Subfamily V Transient Receptor Potential Cation Channel is a mechanically and thermally sensitive ion channel that plays a crucial role in neural growth and development. Using a novel modeling technique, we endeavored to develop an animal model of Bell's palsy and determine whether TRPV2 expression is altered throughout the course of a facial nerve injury. MATERIALS AND METHODS: The rats were categorized into 3 groups, and their facial nerve function was assessed using RT-qPCR, WB, and pathologic testing, respectively, after undergoing unilateral cold air stimulation for 1, 3, and 7 days. TRPV2 expression was identified using these techniques. RESULTS: In response to cold stimulation, rats exhibited facial nerve paralysis symptoms, demyelinating lesions in the facial nerve, and increased TRPV2 expression. CONCLUSIONS: Extended cold stimulation of the facial nerve in rats may lead to an imbalance in facial nerve homeostasis and increased TRPV2 expression. These findings will contribute to the understanding of the potential mechanism by which cold stimulation affects the facial nerve. Moreover, this finding implies that TRPV2 could possibly function as an additional diagnostic marker or therapeutic target in the context of Bell's palsy.

Delivery of neurotrophin-3 by RVG-Lamp2b-modified mesenchymal stem cell-derived exosomes alleviates facial nerve injury.

We aim to investigate the effect of RVG-Lamp2b-modified exosomes (exos) loaded with neurotrophin-3 (NT-3) on facial nerve injury. Exos were collected from control cells (Ctrl Exo) or bone marrow mesenchymal stem cells co-transfected with RVG-Lamp2b and NT-3 plasmids (RVG-NT-3 Exo) by gradient centrifugation and identified by western blotting, transmission electron microscopy, and nanoparticle tracking analysis. Effect of RVG-NT-3 Exo on oxidative stress damage was determined by analysis of the morphology, viability, and ROS production of neurons. Effect of RVG-NT-3 Exo on facial nerve axotomy (FNA) was determined by detecting ROS production, neuroinflammatory reaction, microglia activation, facial motor neuron (FMN) death, and myelin sheath repair. Loading NT-3 and modifying with RVG-Lamp2b did not alter the properties of the exos. Moreover, RVG-NT-3 Exo could effectively target neurons to deliver NT-3. Treatment with RVG-NT-3 Exo lowered H2O2-induced oxidative stress damage in primary neurons and Nsc-34 cells. RVG-NT-3 Exo treatment significantly decreased ROS production, neuroinflammatory response, FMN death, and elevated microglia activation and myelin sheath repair in FNA rat models. Our findings suggested that RVG-NT-3 Exo-mediated delivery of NT-3 is effective for the treatment of facial nerve injury.

Stimulation of trigeminal afferents improves motor recovery after facial nerve injury: functional, electrophysiological and morphological proofs.

Recovery of mimic function after facial nerve transection is poor: the successful regrowth of axotomized motoneurons to their targets is compromised by (1) poor axonal navigation and excessive collateral branching, (2) abnormal exchange of nerve impulses between adjacent regrowing axons, and (3) insufficient synaptic input to facial motoneurons. As a result, axotomized motoneurons get hyperexcitable and unable to discharge. Since improvement of growth cone navigation and reduction of the ephaptic cross talk between axons turn out be very difficult, we concentrated our efforts on the third detrimental component and proposed that an intensification of the trigeminal input to axotomized electrophysiologically silent facial motoneurons might improve specificity of reinnervation. To test our hypothesis we compared behavioral, electrophysiological, and morphological parameters after single reconstructive surgery on the facial nerve (or its buccal branch) with those obtained after identical facial nerve surgery but combined with direct or indirect stimulation of the ipsilateral infraorbital (ION) nerve. We found that in all cases, trigeminal stimulation was beneficial for the outcome by improving the quality of target reinnervation and recovery of vibrissa! motor performance.