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 axotomy induces morphological changes in hippocampal pyramidal neurons.

Facial nerve injury in rats have been widely used to study functional and structural changes that occur in the injured motoneurons and other central nervous system structures related with sensorimotor processing. A decrease in long-term potentiation of hippocampal CA3-to-CA1 commissural synapse has recently been reported related to this peripheral injury. Additionally, it has been found increased corticosterone plasmatic levels, impairment in spatial memory consolidation, and hippocampal microglial activation in animals with facial nerve axotomy. In this work, we analyzed the neuronal morphology of hippocampal CA1 and CA3 pyramidal neurons in animals with either reversible or irreversible facial nerve injury. For this purpose, brain tissues of injured animals sacrificed at different postlesion times, were stained with the Golgi-Cox method and compared with control brains. It was found that both reversible and irreversible facial nerve injury-induced significant decreases in dendritic tree complexity, dendritic length, branch points, and spine density of hippocampal neurons. However, such changes' timing varied according to hippocampal area (CA1 vs. CA3), dendritic area (apical vs. basal), and lesion type (reversible vs. irreversible). In general, the observed changes were transient when animals had the possibility of motor recovery (reversible injury), but perdurable if the recovery from the lesion was impeded (irreversible injury). CA1 apical and CA3 basal dendritic tree morphology were more sensible to irreversible injury. It is concluded that facial nerve injury induced significant changes in hippocampal CA1 and CA3 pyramidal neurons morphology, which could be related to LTP impairments and microglial activation in the hippocampal formation, previously described.

Anticipating Facial Nerve Position Using Three-Dimensional Tractography During the Preoperative Assessment of Cerebellopontine Angle Tumors.

OBJECTIVE: We aim to evaluate the usefulness of preoperative facial nerve tractography in determining the facial nerve position in cerebellopontine angle tumor resection and its value in helping to preserve facial nerve function during surgery. METHODS: A prospective study was designed to include patients presenting with cerebellopontine angle tumors. Three-dimensional reconstruction of facial nerve tractography was performed and added to the usual preoperative testing in all patients. Facial nerve position was compared between tractography results and surgical findings. Moreover, facial nerve function was evaluated at baseline and during follow-up. RESULTS: Fifteen patients were included for analysis. Complete resection was obtained in 5 patients, near-total resection was achieved in 8 patients, and partial resection in 2 patients. We found a strong statistically significant concordance between the preoperative facial nerve tractography reconstruction and the intraoperative findings (complete concordance in 86.66% of all the cases; κ = 0.784; P < 0.0001). Facial nerve anatomic structure was preserved in all patients during surgery. At 6 months follow-up, 66.66% of patients had a facial nerve normal function or a mild dysfunction. CONCLUSIONS: Preoperative facial nerve tractography reconstruction showed a high correlation with intraoperative findings. Preoperative tractography information regarding facial nerve position and its cisternal course is valuable information and could help the surgeon in increasing the safety of the procedure during cerebellopontine angle tumor surgery.

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.

Motoneuron-Specific PTEN Deletion in Mice Induces Neuronal Hypertrophy and Also Regeneration after Facial Nerve Injury.

In postmitotic neurons, several tumor suppressor genes (TSGs), including p53, Rb, and PTEN, modulate the axon regeneration success after injury. Particularly, PTEN inhibition is a key driver of successful CNS axon regeneration after optic nerve or spinal cord injury. In contrast, in peripheral neurons, TSG influence in neuronal morphology, physiology, and pathology has not been investigated to the same depth. In this study, we conditionally deleted PTEN from mouse facial motoneurons (Chat-Cre/PtenloxP/loxP ) and analyzed neuronal responses in vivo with or without peripheral facial nerve injury in male and female mice. In uninjured motoneurons, PTEN loss induced somatic, axonal, and nerve hypertrophy, synaptic terminal enlargement and reduction in physiological whisker movement. Despite these morphologic and physiological changes, PTEN deletion positively regulated facial nerve regeneration and recovery of whisker movement after nerve injury. Regenerating PTEN-deficient motoneurons upregulated P-CREB and a signaling pathway involving P-Akt, P-PRAS40, P-mTOR, and P-4EBP1. In aged mice (12 months), PTEN deletion induced hair loss and facial hyperplasia of the epidermis. This suggests a time window in younger mice with PTEN loss stimulating axon growth after injury, however, at the risk of hyperplasia formation at later time points in the old animal. Overall, our data highlight a dual TSG function with PTEN loss impairing physiological neuron function but furthermore underscoring the positive effects of PTEN ablation in axon regeneration also for the PNS.SIGNIFICANCE STATEMENT Tumor suppressor genes (TSGs) restrict cell proliferation and growth. TSG inhibition, including p53 and PTEN, stimulates axon regeneration after CNS injury. In contrast, in PNS axon regeneration, TSGs have not been analyzed in great depth. Herein we show enhanced peripheral axon regeneration after PTEN deletion from facial motoneurons. This invokes a signaling cascade with novel PTEN partners, including CREB and PRAS40. In adult mice, PTEN loss induces hyperplasia of the skin epidermis, suggesting detrimental consequences when reaching adulthood in contrast to a beneficial TSG role for regeneration in young adult mice. Thus, our data highlight the double-edged sword nature of interfering with TSG function.

Controlled release of ciliary neurotrophic factor from bioactive nerve grafts promotes nerve regeneration in rats with facial nerve injuries.

It is critical to repair severed facial nerves, as lack of treatment may cause long-term motor and sensory impairments. Ciliary neurotrophic factor (CNTF) plays an important role in terms of enhancing nerve axon regrowth and maturation during peripheral nerve regeneration after injury. However, simple application of CNTF to the transected nerve site does not afford functional recovery, because it is rapidly flushed away by bodily fluids. The aim of the present study was the construction of a new, bioactive composite nerve graft facilitating persistent CNTF delivery to aid the reconstruction of facial nerve defects. The in vitro study showed that the bioactive nerve graft generated sustainable CNTF release for more than 25 days. The bioactive nerve graft was then transplanted into the injury sites of rat facial nerves. At 6 and 12 weeks post-transplantation, functional and histological analyses showed that the bioactive nerve graft featuring immobilized CNTF significantly enhanced nerve regeneration in terms of both axonal outgrowth and Schwann cell proliferation in the rat facial nerve gap model, compared to a collagen tube with adsorbed CNTF that initially released high levels of CNTF. The bioactive nerve graft may serve as novel, controlled bioactive release therapy for facial nerve regeneration.

Facial nerve management in patients with malignant skull base tumors.

INTRODUCTION: The course of the facial nerve through the cerebellopontine angle, temporal bone, and parotid gland puts the nerve at risk in cases of malignancy. In contrast to Bell's palsy, which presents with acute facial paralysis, malignancies cause gradual or fluctuating weakness. METHODS: We review malignancies affecting the facial nerve, including those involving the temporal bone, parotid gland, and cerebellopontine angle, in addition to metastatic disease. Intraoperative management of the facial nerve and long term management of facial palsy are reviewed. RESULTS: Intraoperative management of the facial nerve in cases of skull base malignancy may involve extensive exposure, mobilization, or rerouting of the nerve. In cases of nerve sacrifice, primary neurorrhaphy or interposition grafting may be used. Cranial nerve substitution, gracilis free functional muscle transfer, and orthodromic temporalis tendon transfer are management options for long term facial paralysis. CONCLUSION: Temporal bone, parotid gland, and cerebellopontine angle malignancies pose a tremendous risk to the facial nerve. When possible, the facial nerve is preserved. If the facial nerve is sacrificed, static and dynamic reanimation strategies are used to enhance facial function.

Novel Hexb-based tools for studying microglia in the CNS.

Microglia and central nervous system (CNS)-associated macrophages (CAMs), such as perivascular and meningeal macrophages, are implicated in virtually all diseases of the CNS. However, little is known about their cell-type-specific roles in the absence of suitable tools that would allow for functional discrimination between the ontogenetically closely related microglia and CAMs. To develop a new microglia gene targeting model, we first applied massively parallel single-cell analyses to compare microglia and CAM signatures during homeostasis and disease and identified hexosaminidase subunit beta (Hexb) as a stably expressed microglia core gene, whereas other microglia core genes were substantially downregulated during pathologies. Next, we generated HexbtdTomato mice to stably monitor microglia behavior in vivo. Finally, the Hexb locus was employed for tamoxifen-inducible Cre-mediated gene manipulation in microglia and for fate mapping of microglia but not CAMs. In sum, we provide valuable new genetic tools to specifically study microglia functions in the CNS.

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.

Repair of facial nerve crush injury in rabbits using collagen plus basic fibroblast growth factor.

Facial nerves are frequently crushed or cut during facial surgery. In this study, the feasibility of repairing facial nerves in rabbits after crush or cut off injury was evaluated using collagen conduits with A collagen-binding domain (CBD)-human basic fibroblast growth factor (bFGF). A total of 39 six-month-old New Zealand White rabbits were randomly divided into four groups of nine rabbits, and bilateral crush or cut off injuries were made on each animal's face. Three rabbits were classified as the healthy control. The facial nerves were cut or crushed and then were either untreated or wrapped with a collagen conduit plus bFGF. At the 15, 30, and 90 days after the injury, three rabbits in each group were sacrificed. Regeneration of the injured facial nerve was evaluated using electrophysiological examination (compound muscle action potentials, CAMPs), scanning electron microscopy, and histological observation. The results suggested that using collagen conduits with recombinant proteins CBD-bFGF to repair facial nerves with crush or cut off injuries promoted functional facial nerve recovery. This treatment, as a possible therapeutic for patients with facial nerve injury, requires further investigation.

Cautionary Findings for the Presence of Facial Canal Dehiscence During Cholesteatoma Surgery.

Our aim was to investigate the relationship between facial canal dehiscence (FCD) and surgical findings and procedures in patients with cholesteatoma. A total of 186 patients (118 males, 39.2 ± 15 years) who underwent surgery for advanced cholesteatoma between 2013 and 2018 were included in the study. The relationship between FCD and surgical findings was investigated via the surgical registries. The prevalence of FCD was 36.6% (68/186). The prevalence of FCD was 44%, and 13.2% for the patients who underwent canal wall down mastoidectomy (62/141) and canal wall up mastoidectomy (6/45), respectively (P < .001). Facial canal dehiscence was detected in 73.9% of the 23 patients who had a lateral semicircular canal (LSCC) defect (P < .001), in 61.9% of 21 patients who had a tegmen tympani defect, and in 58.1% of the 31 patients who had erosion on the posterior wall of the external auditory canal (EAC; P < .05). The prevalence of FCD was 3.1% in patients with isolated incus erosion, 59.1% in patients with erosion of malleus and incus, 60.7% in patients with erosion of stapes suprastructure and incus, and 43.2% in patients with whole ossicular chain deformation (P < .001). The defects on LSCC, EAC, tegmen tympani, and malleus and incus might be cautionary findings for the presence of FCD during cholesteatoma surgery.

Rat Facial Nerve Regeneration with Human Immature Dental Pulp Stem Cells.

Facial paralysis can result in severe implications for the patients. However, stem cell biology has become an important field in regenerative medicine since the discovery and characterization of mesenchymal stem cells. Our aim was to evaluate the regeneration after facial nerve crush injury and application of human immature dental pulp stem cells (iDPSC). For this study 70 Wistar rats underwent a unilateral facial nerve crush injury and were divided into two groups: Group I (GI): Crushed; Group II (GII): Crushed and iDPSC, and distributed into study periods of 3, 7, 14, 21, and 42 postoperative days. Facial nerve regeneration was analyzed via functional recovery of whisker movement, histomorphometric analysis, and immunoblotting assay. The results show that GII had complete functional recovery at 14 days, while GI recovered after 42 days. Also, regarding the facial nerve trunk, GII presented histological improvement, evidencing better axonal and structural organization of the myelin sheath, and exhibited statistically higher values for the outer and inner perimeters and g-ratio. Nevertheless, GI exhibited statistically higher values for the thickness of myelin sheath. In the buccal branch, no differences were observed for all parameters between groups. At 42 days, both groups GI and GII were close to the levels observed for the control group. Concerning nerve growth factor expression, GII exhibited statistically greater values (p < 0.05) compared with the control group at 7 days. In summary, a single injection of human iDPSC promoted a positive effect on regeneration of the facial nerve trunk after 14 days and provided an alternative to support regeneration following peripheral nerve injury.

Is there a relationship between mastoid pneumatisation and facial canal dimensions?

OBJECTIVE: To evaluate mastoid pneumatisation and facial canal dimensions. METHOD: In this retrospective study, 169 multidetector computed tomography scans of temporal bone were reviewed. Facial canal dimensions were evaluated at the labyrinthine, tympanic and mastoid segments using axial and coronal multidetector computed tomography scans of temporal bone. Mastoid pneumatisation and facial canal dehiscence were evaluated. Facial canal dehiscence was measured if it was found to be present. RESULTS: This study showed that facial canal dimensions decreased in pneumatised mastoids. Facial canal dimensions in females were smaller than in males. Facial canal dehiscence was detected in 5.9 per cent and 6.5 per cent of the patients on the right and left sides, respectively. No correlations were found between facial canal dehiscence and mastoid pneumatisation. The length of dehiscence was 1.92 ± 0.44 mm (range, 0.86-2.51 mm) on the left side. In older subjects, left facial canal dehiscence was detected more, and the length of the dehiscence increased. CONCLUSION: This study concluded that during surgery, facial canal dehiscence should be kept in mind in order to avoid complications.

Brief Electrical Stimulation Improves Functional Recovery After Femoral But Not After Facial Nerve Injury in Rats.

Brief low-frequency electrical stimulation (ES, 1 h, 20 Hz) of the proximal nerve stump has emerged as a potential adjunct treatment for nerve injury. Despite available experimental and clinical data, the potentials and limitations of the ES therapy still have to be defined using different animal models, types of nerves, and clinical settings. Here, we show that brief ES of the proximal stump of the transected rat femoral nerve causes, as estimated by motion analysis, enhanced functional recovery reaching preoperative levels within 5 months of injury, in contrast to the incomplete restoration in sham-stimulated (SS) animals. The functional advantage seen in ES rats was associated with higher numbers, as compared with SS, of correctly targeted quadriceps motoneurons. In contrast, ES prior to facial nerve suture did not lead to improvement of whisking compared with SS. Lack of functional effects of the treatment was correlated with lack of changes, as compared with SS, in the precision of muscle reinnervation and frequency of abnormally innervated muscle fibers. These results show that ES is an effective therapy in a spinal nerve injury model leading to complete restoration of function. Although this finding and the safety of the procedure are encouraging, the results for the facial nerve model suggest that brief ES may not be a universal treatment for nerve injuries. Anat Rec, 302:1304-1313, 2019. © 2019 Wiley Periodicals, Inc.

Mechanisms of the Immunomodulation Effects of Bone Marrow-Derived Mesenchymal Stem Cells on Facial Nerve Injury in Sprague-Dawley Rats.

Normal facial nerve (FN) function is very important for human being. However, if injured, FN function is difficult to restore completely. Recently, many studies reported the immune regulation function of stem cells (SCs). However, the immunomodulation function of SCs on FN injury is still unclear. Our study aims to explore the mechanism of immunomodulation effect of Sprague-Dawley rat bone marrow-derived SCs (BMSCs) on FN injury and specially focus on the regulation of Th17 and the protection effects of BMSCs on central facial motor neurons (FMNs). First, rat FNs were harvested. FN and BMSCs were cultured together or separately and levels of transforming growth factor (TGF)-ß1, interleukin (IL)-6, hepatocyte growth factor (HGF), inducible nitric oxide synthase (iNOS), and prostaglandin E2 (PGE2) in supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Then, after treating with or without local BMSCs injection, the proportion of Th17 in neck lymph nodes (LNs) was investigated in rat FN injury models. Furthermore, the apoptotic index of FMNs was studied in rat FN injury models that were treated with or without BMSCs. We found that BMSCs could secrete high levels of IL-6, HGF, PGE2, iNOS, and TGF-ß1 in culture. The percentage of Th17 of neck LNs in BMSCs-treated group was significantly lower than that in the control group. The apoptotic index of FMNs in BMSCs-treated group was significantly lower than that in the control group. In conclusion, our research indicates BMSCs could independently secrete cytokines IL-6, HGF, PGE2, iNOS, and TGF-ß1, and these cytokines could regulate the balance among subsets of CD4+ T cells and could protect FMNs by inhibiting neuron apoptosis.

Regenerative Failure Following Rat Neonatal Chorda Tympani Transection is Associated with Geniculate Ganglion Cell Loss and Terminal Field Plasticity in the Nucleus of the Solitary Tract.

Neural insult during development results in recovery outcomes that vary dependent upon the system under investigation. Nerve regeneration does not occur if the rat gustatory chorda tympani nerve is sectioned (CTX) during neonatal (≤P10) development. It is unclear how chorda tympani soma and terminal fields are affected after neonatal CTX. The current study determined the impact of neonatal CTX on chorda tympani neurons and brainstem gustatory terminal fields. To assess terminal field volume in the nucleus of the solitary tract (NTS), rats received CTX at P5 or P10 followed by chorda tympani label, or glossopharyngeal (GL) and greater superficial petrosal (GSP) label as adults. In another group of animals, terminal field volumes and numbers of chorda tympani neurons in the geniculate ganglion (GG) were determined by labeling the chorda tympani with DiI at the time of CTX in neonatal (P5) and adult (P50) rats. There was a greater loss of chorda tympani neurons following P5 CTX compared to adult denervation. Chorda tympani terminal field volume was dramatically reduced 50 days after P5 or P10 CTX. Lack of nerve regeneration after neonatal CTX is not caused by ganglion cell death alone, as approximately 30% of chorda tympani neurons survived into adulthood. Although the total field volume of intact gustatory nerves was not altered, the GSP volume and GSP-GL overlap increased in the dorsal NTS after CTX at P5, but not P10, demonstrating age-dependent plasticity. Our findings indicate that the developing gustatory system is highly plastic and simultaneously vulnerable to injury.

Collagen/ß-TCP nerve guidance conduits promote facial nerve regeneration in mini-swine and the underlying biological mechanism: A pilot in vivo study.

This study aimed to evaluate the efficiency of new nerve guidance conduits (NGCs) in bridging facial nerve gaps, and investigate the underlying biological mechanisms implicated in the regeneration process. A collagen/ß-TCP conduit was prepared and applied to a facial nerve gap in a mini-swine model. Functional recovery and axonal regeneration were further evaluated by electrophysiological and histological examinations at 3 months after surgery. Furthermore, the global transcriptomic profiles of regenerated and normal tissues were analyzed by gene microarray to identify the differentially expressed genes at day three and seven, postoperatively. Subsequently, associated biological processes were analyzed by gene ontology (GO) enrichment analysis. The electrophysiological examination and morphological analysis revealed that significant nerve regeneration effects were achieved in the Col/ß-TCP group (p < 0.05). Transcriptional analysis revealed that at day three post-surgery, the majority of overexpressed genes were associated with inflammatory, immune and stimuli response, accompanied by angiogenesis, while at day seven, the majority of overexpressed genes were associated with cell, tissue and organ regeneration and development, synaptic transmission, neurogenesis, and neuronal differentiation, as well as the WNT, MAPK/ERK, and JAK/STAT signaling pathways. In conclusion, the present results suggest that collagen/ß-TCP NGCs provide a promising tubular micro-environment for nerve regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1122-1131, 2019.

CXCL12 has therapeutic value in facial nerve injury and promotes Schwann cells autophagy and migration via PI3K-AKT-mTOR signal pathway.

Facial nerve injury is a clinically common disease accompanied by demyelination of damaged nerves. The remyelination of damaged nerves and the unsatisfactory function recovery are problems that have been plaguing people for a long time. The role that CXCL12 plays after facial nerve injury remains unknown. Our experiments found that the expression of CXCL12 was up-regulated in the early stage of facial nerve injury and decreased after two weeks. Further research found that CXCL12 had no effect on Schwann cells proliferation, apoptosis and cell cycle, while significantly promoted Schwann cells migration. Treatment with CXCL12 decreased the phosphorylation of PI3K, AKT and mTOR, but increased autophagy marker LC3II/I. The CXCL12-induced Schwann cells migration was significantly attenuated by inhibition of autophagy and activation of PI3K pathway through pretreatment with 3-MA and IGF-1 respectively, and this effect was enhanced by PI3K pathway inhibitor LY294002. Animal experiment also confirmed that CXCL12 could improve facial nerve function and myelin regeneration. The findings of this study indicate that CXCL12 can promote the migration of Schwann cells and potentially become a key molecule in the repair of facial nerve injury.

Bilateral Post-Traumatic Facial Paralysis That Contains Longitudinal and Transverse Temporal Fracture.

Acute bilateral post-traumatic facial paralysis is rare in the literature. Post-traumatic facial paralysis is frequently accompanied transverse fractures of temporal more. The incidence of acute bilateral post-traumatic facial paralysis has been reported as 1 to 5 per million in the literature. Trauma and concurrent facial paralysis are usually in the same subsite (right temporal bone fracture and right facial paralysis). There is one pathophysiological pattern for a single temporal bone fracture in a subsite. The authors present a bilateral isolated different pathophysiological pattern sudden onset facial paralysis in a patient herein.

Identification of a resilient mouse facial motoneuron population following target disconnection by injury or disease.

BACKGROUND: When nerve transection is performed on adult rodents, a substantial population of neurons survives short-term disconnection from target, and the immune system supports this neuronal survival, however long-term survival remains unknown. Understanding the effects of permanent axotomy on cell body survival is important as target disconnection is the first pathological occurrence in fatal motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). OBJECTIVE: The goal of this study was to determine if facial motoneurons (FMN) could survive permanent target disconnection up to 26 weeks post-operation (wpo) after facial nerve axotomy (FNA). In addition, the potentially additive effects of immunodeficiency and motoneuron disease on post-axotomy FMN survival were examined. METHODS: This study included three wild type (WT) mouse strains (C57BL/6J, B6SJL, and FVB/NJ) and three experimental models (RAG-2-/-: immunodeficiency; mSOD1: ALS; Smn-/-/SMN2+/+: SMA). All animals received a unilateral FNA, and FMN survival was quantified at early and extended post-operative timepoints. RESULTS: In the C57BL/6J WT group, FMN survival significantly decreased at 10 wpo (55±6%), and then remained stable out to 26 wpo (47±6%). In the RAG-2-/- and mSOD1 groups, FMN death occurred much earlier at 4 wpo, and survival plateaued at approximately 50% at 10 wpo. The SMA model and other WT strains also exhibited approximately 50% FMN survival after FNA. CONCLUSION: These results indicate that immunodeficiency and motoneuron disease accelerate axotomy-induced neuron death, but do not increase total neuron death in the context of permanent target disconnection. This consistent finding of a target disconnection-resilient motoneuron population is prevalent in other peripheral nerve injury models and in neurodegenerative disease models as well. Characterization of the distinct populations of vulnerable and resilient motoneurons may reveal new therapeutic approaches for injury and disease.