Appropriate dosage, timing, and site of intramuscular injections of brain-derived neurotrophic factor (BDNF) promote motor recovery after facial nerve injury in rats.

INTRODUCTION/AIMS: Daily intramuscular injections of fibroblast growth factor 2 (FGF2) but not of brain-derived neurotrophic factor (BDNF) significantly improve whisking behavior and mono-innervation of the rat levator labii superioris (LLS) muscle 56 days after buccal nerve transection and suture (buccal-buccal anastomosis, BBA). We explored the dose-response of BDNF, FGF2, and insulin growth factor 2 (IGF2) on the same parameters, asking whether higher doses of BDNF would promote recovery. METHODS: After BBA, growth factors were injected (30 µL volume) daily into the LLS muscle over 14, 28, or 56 days. At 56 days, video-based motion analysis of vibrissal whisking was performed and the extent of mono- and poly-reinnervation of the reinnervated neuromuscular junctions (NMJs) of the muscle determined with immunostaining of the nerve with ß-tubulin and histochemical staining of the endplates with Alexa Fluor 488-conjugated α-bungarotoxin. RESULTS: The dose-response curve demonstrated significantly higher whisking amplitudes and corresponding increased mono-innervation of the NMJ in the reinnervated LLS muscle at concentrations of 20-30 µg/mL BDNF administered daily for 14-28 days after BBA surgery. In contrast, high doses of IGF2 and FGF2, or doses of 20 and 40 µg/mL of BDNF administered for 14-56 days had no effect on either whisking behavior or in reducing poly-reinnervation of endplates in the muscle. DISCUSSION: These data suggest that the re-establishment of mono-innervation of whiskerpad muscles and the improved motor function by injections of BDNF into the paralyzed vibrissal musculature after facial nerve injury have translation potential and promote clinical application.

Sustained Release In Situ Thermogelling Hydrogel of Cerebrolysin for Treatment of Facial Nerve Axotomy in Rats.

PURPOSE: The most essential principle in managing facial nerve (FN) injury is proper diagnosis and early treatment. This study evaluated local application of different concentrations and injection intervals of Cerebrolysin hydrogel (CBLH) for facial nerve axotomy (FNA) treatment. We hypothesized that local application of CBLH may provide a sustained release of Cerebrolysin and enhance neural regeneration. METHODS: The authors implemented a randomized, controlled, blinded animal study. The sample was composed of the right FN. Functionally, eye-blink reflex was evaluated 2 and 4 weeks postoperatively. All rats were euthanized after 4 weeks, and nerve regeneration was evaluated histopathologically and immunohistochemically (IHC) with antibody against neurofilament (anti-NF) and S100 proteins. Descriptive and correlation statistics were computed, and the P value was set at .05. RESULTS: The sample was composed of 72 adult male rats equally allocated into 8 groups. Groups I and V served as control groups and were injected with phosphate buffered saline once and four times, respectively. Rest of the groups were injected with 5%, 10%, and 15% CBLH once in groups II, III, IV and weekly in groups VI, VII, and VIII. CBLH showed statistically significant FN regeneration by enhancing Schwann and axonal growth compared to control group especially with single injection of 10%, 15%, and 5% 4-time injections, where the P value was less than .001. Significant improvement of eye-blink reflex was correlated with structural improvement associated with CBLH. CONCLUSION: Finally, CBLH enhanced nerve regeneration and rehabilitation after FNA in rats. Therefore, it could be considered as an alternative treatment of FNA. More experimental and clinical trials should be considered to detect the effectiveness of CBLH in neural regeneration.

Is Decorin a Promising New Agent for Facial Nerve Regeneration? An Experimental Study.

OBJECTIVE: The aim of this study was to investigate the effects of systemic administration of decorin (DC) on facial nerve (FN) regeneration. METHODS: A total of 32 female albino Wistar rats were divided into 4 groups: control (C) group: no bilateral FN neurorrhaphy (B-FNN), no DC application, sham-operated group: B-FNN without DC application, DC group: DC application without B-FNN, and B-FNN + DC group: B-FNN and DC application. Nerve conduction studies were performed before and after skin incisions at 1st, 3rd, 5th, and 7th weeks in all groups. The amplitude and latency of compound muscle action potentials were recorded. FN samples were obtained and were investigated under light microscopy and immunohistochemical staining. The nerve and axon diameter, number of axons, H score, Schwann cell proliferation, and myelin and axonal degeneration were recorded quantitatively. RESULTS: In the sham group, the 3rd and 5th postoperative week, amplitude values were significantly lower than those of the B-FNN + DC group (p < 0.05). Nerve diameters were found to be significantly larger in the sham, DC, and B-FNN + DC groups than in the C group (p < 0.05). The number of axons, the axon diameter, and the H scores were found to be significantly higher in the B-FNN + DC group than in the sham group (p < 0.05). The Schwann cell proliferation, myelin degeneration, and axonal degeneration scores were significantly lower in the B-FNN + DC group than in the sham group (p < 0.05). CONCLUSION: Electrophysiological and histopathological evaluation revealed the potential benefits provided by DC. This agent may increase FN regeneration.

The effects of 4-aminopyridine and methylprednisolone on recovery of the facial nerve crush injury.

OBJECTIVE: 4-Aminopyridine (4-AP) is a potassium channel blocker that enhances nerve excitability. In this study, rat models that have facial nerve crush injury (FNCI) were grouped and treated with methylprednisolone (MP), 4-AP, and a combination of these two drugs. Electrophysiologic and histopathologic outcomes of these groups will be compared with a control group. MATERIALS AND METHODS: Thirty healthy male Wistar rats (mean weight of 265 g) were used in this study. The rats were randomly divided into five groups with six subjects in each: Group 1 (sham group), Group 2 (control group), Group 3 (MP group), Group 4 (4-aminopyridine group), and Group 5 (4-AP + MP group). All groups except the sham group underwent crush injury to the right facial nerve. Electrophysiologic and histologic recovery was recorded three weeks postoperatively. RESULTS: The 4-AP group and the combined group had a more significant recovery at Nerve Excitability Thresholds (NET) at the end of three weeks. The methylprednisolone group and the control group had a minimal recovery of NET. Histologically, when compared with the control group, the combined group was the only group that had significant recovery at all three of axonal degeneration, axon diameter, and myelin thickness. CONCLUSION: In this experimental study, we demonstrated that a combination treatment of 4-AP and MP is more effective in the recovery of peripheric FNCI than in the no-treatment control group and in the 4-AP- or MP-alone groups. Moreover, our results suggested that 4-AP can be a potent alternative to MP in the treatment of the FNCI. LEVEL OF EVIDENCE: N/A.

Neuroprotective Effect of Brimonidine against Facial Nerve Crush Injury in Rats via Suppressing GFAP/PAF Activation and Neuroinflammation.

OBJECTIVE: This study aimed to investigate the potential neuroprotective action of brimonidine against facial nerve crush injury in rats and the possible underlying mechanisms. METHODS: Sixty Wistar adult rats were randomly and equally divided into 3 groups: 40 rats underwent unilateral facial nerve crush injury and were administered with either saline (intraperitoneal, n = 20) or brimonidine 1 mg/kg/day (intraperitoneal, n = 20) for 5 consecutive days. Functional and electromyographic recovery was recorded postoperatively. The facial nucleus of 5 mice in each group was analyzed for mRNA expression levels of GFAP, PAF, NT-4, P75NTR, NF-κB, TNF-α, IL-6, and α2-ARs by qRT-PCR. RESULTS: Brimonidine promoted the recovery of vibrissae movement, eyelid closure, and electrophysiological function in a rat model of nerve crush injury. Hematoxylin and eosin staining and electron microscopy showed significant recovery of Schwann cells and axons in the brimonidine group. Brimonidine attenuated the crush-induced upregulation in GFAP and PAF mRNA (p < 0.05), as well as enhanced the mRNA levels of NT-4 and P75NTR (p < 0.05), while decreased the expression of NF-κB, TNF-α and IL-6 (p < 0.05). CONCLUSIONS: Brimonidine could promote the recovery of facial nerve crush injury in rats via suppressing of GFAP/PAF activation and neuroinflammation and increasing neurotrophic factors. Brimonidine may be apromising candidate agent for the treatment of facial nerve injury.

Neutralizing BDNF and FGF2 injection into denervated skeletal muscle improve recovery after nerve repair.

BACKGROUND: After facial nerve injury and surgical repair in rats, recovery of vibrissal whisking is associated with a high proportion of mono-innervated neuro-muscular junctions (NMJs). Our earlier work with Sprague Dawley (SD)/Royal College of Surgeons (RCS) rats, which are blind and spontaneously restore NMJ-monoinnervation and whisking, showed correlations between functional recovery and increase of fibroblast growth factor-2 (FGF2) and brain-derived neurotrophic factor (BDNF) in denervated vibrissal muscles. METHODS: We used normally sighted rats (Wistar), in which NMJ-polyinnervation is highly correlated with poor whisking recovery, and injected the vibrissal muscle levator labii superioris (LLS) with combinations of BDNF, anti-BDNF, and FGF2 at different postoperative periods after facial nerve injury. RESULTS: Rats receiving anti-BDNF+FGF2 showed low NMJ-polyinnervation and best recovery of whisking amplitude. CONCLUSIONS: Restoration of target reinnervation after peripheral nerve injury requires a complex mixture of trophic factors with a specific time course of availability for each of them.

[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.

The effect of tacrolimus on facial nerve injury: Histopathological findings in a rabbit model.

HYPOTHESIS: Tacrolimus helps healing of facial nerve injury. BACKGROUND: Positive effects of tacrolimus on axon regeneration and healing of injured peripheral nerves (eg. sciatic nerve) have been reported in the literature. Tacrolimus may be an additional treatment method that could improve the nerve healing after surgical treatment of cut injury of facial nerve. METHODS: 20 New Zealand rabbits were randomly separated into control and study groups of 10. In control group, no medical treatment was given after facial nerve anastomosis, and the animals were followed up for 2months. In the study group rabbits were given 1mg/kg/day tacrolimus subcutaneously for 2months after the facial nerve anastomosis. The histopathologic findings of axon regeneration like axon myelination were analyzed in both groups under electron and light microscopy. The data obtained in the groups were compared. RESULTS: Greater axon diameters, thicker myelin sheaths, and higher total number of myelinated axons were found in the tacrolimus group, suggesting better regeneration in this group when compared to the control group. There was less vacuolar degeneration in the study group. All these findings suggest that tacrolimus positively affects healing after facial nerve anastomosis. CONCLUSION: The results of this study indicate that tacrolimus has favorable effects on the healing process of the facial nerve after end-to-end anastomosis. Tacrolimus may be a promising agent in the future for nerve regeneration following traumatic facial paralysis surgery.

Effect of FK506 on apoptosis of facial motor neurons in rats and its possible mechanism.

To investigate the effect of FK506 on apoptosis of facial motor neurons in rats and its possible mechanism. A total of 48 Wistar rats were randomly divided into experimental group and control group. Facial nerve injury model was established by transection of facial nerve at stylomastoid foramen. Rats in experimental group and control group were provided with FK506 and normal saline by intraperitoneal injection, respectively. The morphology of facial neurons was observed under light microscope at different time points after injury. Apoptotic facial motor neurons were detected by TdT-mediated dUTP-biotin nick and labeling (TUNEL) staining, and expression of bcl-2 and bax was evaluated by immunohistochemistry. After facial nerve transection, the apoptotic cells in experimental group significantly decreased compared to control group (P < 0.05), with higher expression of bcl-2 and lower expression of bax in experimental group. FK506 could inhibit apoptosis of facial motor neurons after facial nerve transection, possibly via up-regulation of bcl-2 expression and down-regulation of bax expression.

Vitamin D3 potentiates myelination and recovery after facial nerve injury.

Roles of vitamin D on the immune and nervous systems are increasingly recognized. Two previous studies demonstrated that ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) induced functional recovery and increased myelination in a rat model of peroneal nerve transection. The current report assessed whether cholecalciferol was efficient in repairing transected rabbit facial nerves. Animals were randomized into two groups of rabbits with an unilateral facial nerve surgery: the vitamin D group included animals receiving a weekly oral bolus of vitamin D3 (200 IU/kg/day), from day 1 post-surgery; the control group included animals receiving a weekly oral bolus of vehicle (triglycerides). Contralateral unsectioned facial nerves from all experimental animals were used as controls for the histological study. The facial functional index was measured every week while the inner diameter of myelin sheath and the G ratio were quantified at the end of the 3 month experiment. The current report indicates that cholecalciferol significantly increases functional recovery and myelination, after 12 weeks of treatment. To the best of our knowledge, this is the first study investigating the therapeutic benefit of vitamin D supplementation in an animal model of facial paralysis. It paves further the way for clinical trials based on the administration of this steroid in individuals with injured facial nerves.

The effect of memantine on functional recovery of the facial nerve after crush injury.

The objective of this study is to establish whether memantine is an alternative and effective treatment on facial nerve recovery after crush injury, and also to analyze the effective doses of this promising agent. This is a randomized controlled animal study. 40 rats underwent crush injury to left main trunk of the facial nerve, and divided into 4 groups; (1) control (saline treated), (2) 5-mg/kg memantine, (3) 10-mg/kg memantine, and (4) 20-mg/kg memantine group. Facial nerve functions were evaluated by eye reflex, and whisker movement compared to the unaffected side. They were scored on a 3-point scale. On day 28, the rats were sacrificed, and the facial nerves were dissected. The paraffin sections were studied with caspase-3 immunostaining. According to statistical data, the recovery in Group 4 began significantly earlier than the other groups on the basis of restoring eye blink reflexes and whisker movement. Groups 2 and 3 showed faster recovery than Group 1 on the basis of whisker movement. The caspase-3 positive staining was rarely detected in all groups. The Kruskal­Wallis test revealed that Group 4 showed fewer apoptotic cells than other groups; this was statistically significant. However, the Mann­Whitney U test with the Bonferroni correction did not reveal any significant difference between the groups. In conclusion, this study revealed that memantine acted to restore facial nerve functions, and accelerate recovery after facial nerve injury by inhibiting apoptosis.

The effect of coenzyme Q10 on the regeneration of crushed facial nerve.

OBJECTIVE: The aim of this study is to show the possible positive effect of coenzyme Q10 (Co Q10) on regenerating in facial palsy. MATERIALS AND METHODS: Sixteen female Sprague-Dawley albino rats were randomly divided into 2 groups as Co Q10 and control groups. Group Q10 (n = 8) received Co Q10 of 10 mg/kg/d intraperitoneally for 30 days, and group C (n = 8) received saline solution of 1 mL/d intraperitoneally once daily for 30 days. The right facial nerve stimulation thresholds were determined before crush, immediately after crush, and after 1 month.After determination of the thresholds, the crushed part of the facial nerve was then excised. All specimens were examined by a pathologist using a light microscope. RESULTS: No statistically significant difference in stimulation threshold was found between the Co Q10 and saline groups after crushing (P = 0.645). After 1 month of treatment, stimulation thresholds were significantly lower in both the Co Q10 and saline groups (Ps = 0.028 and 0.016). However, the Co Q10 group showed greater improvement than the saline group (P = 0.050).After 1 month of treatment, neither the Co Q10 group nor the saline group had reached the precrushing amplitude levels (Ps = 0.027 and 0.011).Significant differences were found in vascular congestion, macrovacuolization, and myelin thickness between the Co Q10 and control groups by light microscopy (P < 0.05). CONCLUSIONS: Although many treatment methods have been tried to accelerate facial nerve regeneration after trauma, a definitive method has not been found yet. Co Q for the treatment of acute facial paralysis is promising on both physiologic assessments and pathologic evaluation.

Nerve growth factor reduces apoptotic cell death in rat facial motor neurons after facial nerve injury.

OBJECTIVE: To assess the effects of nerve growth factor (NGF) on motor neurons after induction of a facial nerve lesion, and to compare the effects of different routes of NGF injection on motor neuron survival. METHODS: This study was carried out in the Department of Otolaryngology Head & Neck Surgery, China Medical University, Liaoning, China from October 2012 to March 2013. Male Wistar rats (n = 65) were randomly assigned into 4 groups: A) healthy controls; B) facial nerve lesion model + normal saline injection; C) facial nerve lesion model + NGF injection through the stylomastoid foramen; D) facial nerve lesion model + intraperitoneal injection of NGF. Apoptotic cell death was detected using the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. Expression of caspase-3 and p53 up-regulated modulator of apoptosis (PUMA) was determined by immunohistochemistry. RESULTS: Injection of NGF significantly reduced cell apoptosis, and also greatly decreased caspase-3 and PUMA expression in injured motor neurons. Group C exhibited better efficacy for preventing cellular apoptosis and decreasing caspase-3 and PUMA expression compared with group D (p<0.05). CONCLUSION: Our findings suggest that injections of NGF may prevent apoptosis of motor neurons by decreasing caspase-3 and PUMA expression after facial nerve injury in rats. The NGF injected through the stylomastoid foramen demonstrated better protective efficacy than when injected intraperitoneally.

[The use of botulinum toxin type a in the acute phase of facial nerve injury after neurosurgical surgery].

AIM: To evaluate the role of botulinum toxin type A in the acute phase of facial nerve injury after neurosurgical surgery. MATERIALS AND METHODS: The study involved 55 patients with acute facial muscle paresis caused by facial nerve injury during surgery on the posterior cranial fossa and cerebello-pontine angle (CPA). The first group consisted of 35 patients (mean age, 48.14±1.26 years) who were administered botulinum toxin type A (xeomin) at a dose of 2-3 U per point in muscles of the intact side of the face. The control group included 20 patients (mean age, 49.85±1.4 years) who underwent standard rehabilitation treatment of this pathology. The treatment efficacy was evaluated using the House-Brackmann Scale, the Yanagihara facial grading system, the Facial Disability Index (FDI), and the Sunnybrook Facial Grading (SFG) Scale. RESULTS: Before treatment, patients of both groups experienced severe dysfunction according to the House-Brackmann Scale. A month after the botulinium toxin type A therapy had been started, a significant improvement in the group of patients who received botulinum toxin was observed at all scales (p<0.05), whereas improvement in the facial nerve function in the second group was observed only by the 3rd month of rehabilitation treatment (p<0.05). The number of synkineses in the patients who did not receive botulinum toxin was 46% higher than that in the first group (p=0.019) one year after the surgery, and it was higher by 91% after 2 years (p<0.001). CONCLUSIONS: The use of botulinum toxin type A is reasonable in acute facial nerve injury and should be mandatory in combined therapy of these patients.

Localized application of SAG21k-loaded fibrin hydrogels for targeted modulation of the hedgehog pathway in facial nerve injury.

Given the broad biological effects of the Hedgehog (Hh) pathway, there is potential clinical value in local application of Hh pathway modulators to restrict pathway activation of target tissues and avoid systemic pathway activation. One option to limit Hh pathway activation is using fibrin hydrogels to deliver pathway modulators directly to tissues of interest, bypassing systemic distribution of the drug. In this study, we loaded the potent Hh pathway agonist, SAG21k, into fibrin hydrogels. We describe the binding between fibrin and SAG21k and achieve sustained release of the drug in vitro. SAG21k-loaded fibrin hydrogels exhibit strong biological activity in vitro, using a pathway-specific reporter cell line. To test in vivo activity, we used a mouse model of facial nerve injury. Application of fibrin hydrogels is a common adjunct to surgical nerve repair, and the Hh pathway is known to play an important role in facial nerve injury and regeneration. Local application of the Hh pathway agonist SAG21k using a fibrin hydrogel applied to the site of facial nerve injury successfully activates the Hh pathway in treated nerve tissue. Importantly, this method appears to avoid systemic pathway activation when Hh-responsive organs are analyzed for transcriptional pathway activation. This method of local tissue Hh pathway agonist administration allows for effective pathway targeting surgically accessible tissues and may have translational value in situations where supranormal pathway activation is therapeutic.

Evoked electromyography to rocuronium in orbicularis oris and gastrocnemius in facial nerve injury in rabbits.

BACKGROUND: Muscles innervated by the facial nerve show different sensitivities to muscle relaxants than muscles innervated by somatic nerves, especially in the presence of facial nerve injury. We compared the evoked electromyography (EEMG) response of orbicularis oris and gastrocnemius in with and without a non-depolarizing muscle relaxant in a rabbit model of graded facial nerve injury. METHODS: Differences in EEMG response and inhibition by rocuronium were measured in the orbicularis oris and gastrocnemius muscles 7 to 42 d after different levels of facial nerve crush injuries in adult rabbits. RESULTS: Baseline EEMG of orbicularis oris was significantly smaller than those of the gastrocnemius. Gastrocnemius was more sensitive to rocuronium than the facial muscles (P < 0.05). Baseline EEMG and EEMG amplitude of orbicularis oris in the presence of rocuronium was negatively correlated with the magnitude of facial nerve injury but the sensitivity to rocuronium was not. No significant difference was found in the onset time and the recovery time of rocuronium among gastrocnemius and normal or damaged facial muscles. CONCLUSIONS: Muscles innervated by somatic nerves are more sensitive to rocuronium than those innervated by the facial nerve, but while facial nerve injury reduced EEMG responses, the sensitivity to rocuronium is not altered. Partial neuromuscular blockade may be a suitable technique for conducting anesthesia and surgery safely when EEMG monitoring is needed to preserve and protect the facial nerve. Additional caution should be used if there is a risk of preexisting facial nerve injury.

Beneficial Effect of Bee Venom and Its Major Components on Facial Nerve Injury Induced in Mice.

Peripheral nerve injury (PNI) is a health problem that affects many people worldwide. This study is the first to evaluate the potential effect of bee venom (BV) and its major components in a model of PNI in the mouse. For that, the BV used in this study was analyzed using UHPLC. All animals underwent a distal section-suture of facial nerve branches, and they were randomly divided into five groups. Group 1: injured facial nerve branches without any treatment. Group 2: the facial nerve branches were injured, and the normal saline was injected similarly as in the BV-treated group. Group 3: injured facial nerve branches with local injections of BV solution. Group 4: injured facial nerve branches with local injections of a mixture of PLA2 and melittin. Group 5: injured facial nerve branches with local injection of betamethasone. The treatment was performed three times a week for 4 weeks. The animals were submitted to functional analysis (observation of whisker movement and quantification of nasal deviation). The vibrissae muscle re-innervation was evaluated by retrograde labeling of facial motoneurons in all experimental groups. UHPLC data showed 76.90 ± 0.13%, 11.73 ± 0.13%, and 2.01 ± 0.01%, respectively, for melittin, phospholipase A2, and apamin in the studied BV sample. The obtained results showed that BV treatment was more potent than the mixture of PLA2 and melittin or betamethasone in behavioral recovery. The whisker movement occurred faster in BV-treated mice than in the other groups, with a complete disappearance of nasal deviation two weeks after surgery. Morphologically, a normal fluorogold labeling of the facial motoneurons was restored 4 weeks after surgery in the BV-treated group, but no such restoration was ever observed in other groups. Our findings indicate the potential of the use of BV injections to enhance appropriate functional and neuronal outcomes after PNI.

Effects of platelet-rich fibrin and dexamethasone on nerve regeneration after acute facial-nerve injury.

BACKGROUND: Acute facial-nerve injury. OBJECTIVE: To investigate the effects of platelet-rich fibrin (PRF) and dexamethasone on nerve regeneration. MATERIALS AND METHODS: Thirty-six rats were randomly divided into six groups. Facial-nerve injury was created using a full-thickness incision in all groups except Group E. Next, primary anastomosis, PRF application, topical dexamethasone application, primary anastomosis with topical PRF and dexamethasone application, and no facial-nerve repair were performed in Groups A, B, C, D, and F, respectively. Clinical, functional, and structural improvements were evaluated at eight weeks. RESULTS: The mean eye-closure movement score in Group B was significantly higher than that in Group F (p < .001). The mean whisker-movement score in Group B was significantly higher than that in Group F (p = .001). The mean amplitude of whisker movement in Group F was significantly lower than those in Groups A, B, C, and E, and the mean amplitude in Group D was significantly lower than that in Group E (p < .001). Furthermore, an improvement in nerve ultrastructure was observed in Group B. CONCLUSION: PRF application has a positive effect on nerve recovery after anastomosis. SIGNIFICANCE: Contribute to the literature to improve nerve regeneration.

Distinct neurotoxic effects of select local anesthetics on facial nerve injury and recovery.

BACKGROUND: Local anesthetic toxicity has been well-documented to cause neuronal injury, death, and dysfunction, particularly in a susceptible nerve. OBJECTIVE: To determine whether select local anesthetics affect neuron survival and/or functional recovery of an injured nerve. METHODS: This report describes 6 separate experiments that test immediate or delayed application of local anesthetics in 3 nerve injury models. Adult C57/black6 male mice underwent a facial nerve sham, transection, or crush injury. Local anesthetic or saline was applied to the facial nerve at the time of injury (immediate) or 1 day after injury (delayed). Average percent facial motoneuron (FMN) survival was evaluated four-weeks after injury. Facial nerve regeneration was estimated by observing functional recovery of eye blink reflex and vibrissae movement after facial nerve crush injury. RESULTS: FMN survival after: transection + immediate treatment with ropivacaine (54.8%), bupivacaine (63.2%), or tetracaine (66.9%) was lower than saline (85.5%) and liposomal bupivacaine (85.0%); crush + immediate treatment with bupivacaine (92.8%) was lower than saline (100.7%) and liposomal bupivacaine (99.3%); sham + delayed treatment with bupivacaine (89.9%) was lower than saline (96.6%) and lidocaine (99.5%); transection + delayed treatment with bupivacaine (67.3%) was lower than saline (78.4%) and liposomal bupivacaine (77.6%); crush + delayed treatment with bupivacaine (85.3%) was lower than saline (97.9%) and lidocaine (96.0%). The average post-operative time for mice to fully recover after: crush + immediate treatment with bupivacaine (12.83 days) was longer than saline (11.08 days) and lidocaine (10.92 days); crush + delayed treatment with bupivacaine (16.79 days) was longer than saline (12.73 days) and lidocaine (11.14 days). CONCLUSIONS: Our data demonstrate that some local anesthetics, but not all, exacerbate motoneuron death and delay functional recovery after a peripheral nerve injury. These and future results may lead to clinical strategies that decrease the risk of neural deficit following peripheral nerve blocks with local anesthetics.