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.

Photobiomodulation at a wavelength of 633 nm leads to faster functional recovery than 804 nm after facial nerve injury.

We analyzed the effects of photobiomodulation (PBM) of various wavelengths on regeneration of the facial nerve using in vitro and in vivo experimental models. We assessed the antioxidative effect of PBM in geniculate ganglion neurons irradiated with a diode laser at 633 nm, 780 nm and 804 nm. Wavelengths of 633 and 780 nm but not 804 nm inhibited cell death by oxidative stress. We assessed the effects of PBM on functional and morphologic recovery in rats divided into control, facial nerve damage (FND) and FND irradiated with a 633 nm or 804 nm lasers. Injured rats treated with 633-nm light had better facial palsy scores, larger axon diameter and higher expression of Schwann cells compared with the FND group. No positive results were observed in rats irradiated at 804-nm light. These findings indicate that 633-nm PBM promotes accelerated nerve regeneration and improved functional recovery in an injured facial nerve.

Peripheral trigeminal branch stimulation for refractory facial pain: A single-center experience.

OBJECTIVE: Facial pain refractory to medical treatments may benefit from neurosurgical interventions. Only a few studies have reported on the efficacy of peripheral trigeminal stimulation and more specifically supraorbital nerve (SON) and infraorbital nerve (ION) stimulation for the treatment of facial pain. PATIENTS AND METHODS: In the present study, we identified all patients at our institution who underwent SON and/or ION stimulation for treatment of facial pain due to post-herpetic, traumatic or idiopathic etiology. Relevant pre and post-operative outcomes were analyzed. RESULTS: We identified 15 patients who underwent SON and/or ION stimulation. Among them, 12 (80 %) endorsed >50 % pain relief during the trial stimulation period. After a median follow-up of 5.8 months with permanent implantation, 1 patient (8.3 %) was diagnosed with lead erosion and IPG migration, two patients had lead infections (16.7 %) and one (8.3 %) had wound dehiscence. No lead migrations were identified during the long-term follow-up. The VAS score showed a statistically significant reduction from a median pre-operative score of 7 to a post-operative score of 1.8 (p = 0.011), which corresponded to a 74.3 % average pain reduction. CONCLUSION: SON and/or ION stimulation can be an effective treatment for intractable facial pain due to post-herpetic, traumatic or idiopathic etiology; however the complication rate is relatively high. Future prospective studies with longer follow-up periods are warranted.

[Progress of the Mechanism of Acupuncture to Promote Repair of Facial Nerve Injury].

Facial nerve injury results in facial muscle movement disorders that interferes with patient's life. Acupuncture is an effective therapy for facial nerve injury, but its mechanism has not been clarified. The evidence supports that acupuncture can accelerate the repair of facial nerve injury by adjusting the electric wave of patient's facial muscle, improving facial blood circulation, and promoting the expression of cell and protein molecule.

[Comparative Observation on Electroacupuncture and Manual Acupuncture in Rabbits with Facial Nerve Injury by Electron Microscope].

OBJECTIVE: To observe the effect of manual acupuncture and electroacupuncture (EA) on ultrastructure of facial nerve Schwann cells, myelin sheath and mitochondria in facial nerve injury rabbits, so as to explore its mechanism underlying improving facial palsy. METHODS: A total of 50 New Zealand rabbits were randomly divided into normal, sham-operation, model, MA and EA groups (n=10 in each group). Facial nerve injury model was made by clamping the facial nerve for 5 min using a pair of forceps. Manual needle stimulation (mild reinforcing-reducing) or EA (continuous wave, 20 Hz) was applied to "Dicang" (ST 4), "Xiaguan" (ST 7), "Taiyang" (EX-HN 5) and "Yangbai" (GB 14) on the injured sides for 4 weeks, 30 min each day. The facial nerve motion score was performed every 7 days. The ultrastructure of facial nerve was observed by electron microscope after 28 days' treatment. RESULTS: There were no significant differences in behavioral score and ultrastructure in normal and sham-operation groups (P<0.05). Compared with the normal group, facial nerve motion scores, ultrastructural morphological changes and the number of axons per unit area, myelin sheath thickness and axon area were worse in the model group (P<0.05). After treatment, facial nerve motion scores, ultrastructural morphological changes and the number of axons per unit area, myelin sheath thickness and axon area in the two treatment groups were better than those in the model group (P<0.05), and EA worked better than MA (P<0.05). CONCLUSIONS: In the treatment of facial nerve injury, EA can promote axoplasmic mitochondrial proliferation, myelin sheath recovery and axonal regeneration more effectively than MA, which may be one of the mechanisms that EA therapy is superior to MA.

Stimulation of morphofunctional repair of the facial nerve with photobiomodulation, using the end-to-side technique or a new heterologous fibrin sealant.

This research evaluated the influence of Photobiomodulation Therapy (PBMT) on lesions of the facial nerve repaired with the end-to-side technique or coaptation with a new heterologous fibrin sealant. Thirty-two Wistar rats were separated into 5 groups: Control group (CG), where the buccal branch of the facial nerve was collected; Experimental Suture Group (ESG) and Experimental Fibrin Group (EFG), in which the buccal branch was end-to-side sutured to the zygomatic branch on the right side of the face or coaptated with fibrin sealant on the left side; Experimental Suture Laser Group (ESLG) and Experimental Fibrin Laser Group (EFLG), in which the same procedures were performed as the ESG and EFG, associated with PBMT (wavelength of 830nm, energy density 6.2J/cm2, power output 30mW, beam area of 0.116cm2, power density 0.26W/cm2, total energy per session 2.16J, cumulative dose of 34.56J). The laser was applied for 24s/site at 3 points on the skin's surface, for a total application time of 72s, performed immediately after surgery and 3 times a week for 5weeks. A statistically significant difference was observed in the fiber nerve area between the EFG and EFLG (57.49±3.13 and 62.52±3.56µm2, respectively). For the area of the axon, fiber diameter, axon diameter, myelin sheath area and myelin sheath thickness no statistically significant differences were found (p<0.05). The functional recovery of whisker movement occurred faster in the ESLG and EFLG, which were associated with PBMT, with results closer to the CG. Therefore, PBMT accelerated morphological and functional nerve repair in both techniques.

Electrical response grading versus House-Brackmann scale for evaluation of facial nerve injury after Bell's palsy: a comparative study.

OBJECTIVE: There are no convenient techniques to evaluate the degree of facial nerve injury during a course of acupuncture treatment for Bell's palsy. Our previous studies found that observing the electrical response of specific facial muscles provided reasonable correlation with the prognosis of electroacupuncture treatment. Hence, we used the new method to evaluate the degree of facial nerve injury in patients with Bell's palsy in comparison with the House-Brackmann scale. The relationship between therapeutic effects and prognosis was analyzed to explore an objective method for evaluating Bell's palsy. METHODS: The facial nerve function of 68 patients with Bell's palsy was assessed with both electrical response grading and the House-Brackmann scale before treatment. Then differences in evaluation results of the two methods were compared. All enrolled patients received electroacupuncture treatment with disperse-dense wave at 1/100 Hz for 4 weeks. After treatment, correlation analysis was conducted to find the relationship between electrical response and therapeutic effects or prognosis. RESULTS: Checking consistency between electrical response grading and House-Brackmann scale: Kappa value 0.028 (P = 0.578). Correlation analysis: the two methods were correlated with the prognosis, and electrical response grading (rER = 0.789) was better than the House-Brackmann scale (rHB = 0.423). CONCLUSION: Electrical response grading is superior to the House-Brackmann scale in efficacy and reliability, and can conveniently assess the degree of facial nerve injury. The House-Brackmann scale is suitable for the patients with mild facial nerve injury, but its evaluation quality for severe facial nerve injury is poor.

Hyperbaric oxygen versus steroid in facial nerve injury: an experimental animal study.

OBJECTIVE: The aim of this experimental study was to evaluate the effects of hyperbaric oxygen, methylprednisolone and combined hyperbaric oxygen-methylprednisolone treatments on traumatic facial nerve regeneration in rats. SUBJECTS AND METHODS: After exposure to facial nerve injury, four groups of rats were created with five subjects in each group: Group 1 (hyperbaric oxygen), group 2 (control), group 3 (combined hyperbaric oxygen-methylprednisolone), group 4 (methylprednisolone). Facial nerve specimens from sacrificed animals were examined for axonal degeneration, vascular congestion, macro vacuolization, axon diameter and thickness of myelin sheath. RESULTS: There were significant differences with regard to axonal degeneration, vascular congestion and axon diameter between group 3 and the control group. In addition to lower axonal degeneration and vascular congestion, a larger diameter of axons was observed in group 3. There were significant differences with regard to vascular congestion and axon diameter between group 4 and the control group. We observed thicker myelin and lower axonal degeneration in group 3 compared with group 4. CONCLUSION: The combination therapy with hyperbaric oxygen and methylprednisolone had an additive beneficial effect on regeneration of the facial nerve and may provide better treatment outcomes than methylprednisolone or hyperbaric oxygen therapy alone.

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.

[Effect of electroacupuncture on ultrastructural changes of facial nerve in rabbits with facial nerve injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on ultrastructure of facial nerve and Schwann cells in facial nerve injury rabbits so as to explore its mechanism underlying improving facial palsy. METHODS: A total of 60 Japanese white rabbits were randomly assigned to normal control (normal, n = 6), sham-operation (sham, n = 18), model (n = 18) and EA (n = 18) groups. The facial nerve injury model was established by clamping the right facial nerve for 5 min by using a pair of forceps. EA (1.5 V, 3 Hz/60 Hz) was applied to "Yifeng" (TE 17)-"Hegu" (LI 4), and "Dicang" (ST4)-"Jiache" (ST6) on the affected side for 30 min, respectively, once daily for 3 weeks. Morphologic changes of the myelin sheath and Schwann cells of the facial nerve were observed by using electron microscope after 1, 2 and 3 weeks' treatment. RESULTS: Compared with the normal control group, the number of the myelin sheaths and the thickness values of the facial nerve after treatment of 1, 2 and 3 weeks in the model group were decreased significantly (P < 0.01, P < 0.05). While in comparison with the model group, the thickness value of the facial nerve 2 weeks after modeling in EA group was increased considerably (P < 0.01). In the model group, there were many vacuoles in the cytoplasm of Schwann cells instead of organells in the facial nerve. In the sham group, the demyelination was milder than that of the model group, and majority of myelin sheaths showed integral structure after 2 and 3 weeks, being similar to the normal group. Compared with the model group, the extent of demyelination was less distinct, with relatively more abundant organells in the facial nerve of the EA group, especially after 1 week of treatment. Among the three time points in the EA group, demyelination was milder in the 1st week not in the other time points. In contrast, along with the continuous EA treatment, the situation became worse after 3 weeks of treatment in the EA group. CONCLUSION: In the acute stage of facial nerve injury, EA intervention can play a positive effect on the repair of the nerve and Schwann cells. However, continuous 3- weeks' EA intervention may worsen the facial nerve injury.

Single session of brief electrical stimulation immediately following crush injury enhances functional recovery of rat facial nerve.

Peripheral nerve injuries lead to a variety of pathological conditions, including paresis or paralysis when the injury involves motor axons. We have been studying ways to enhance the regeneration of peripheral nerves using daily electrical stimulation (ES) following a facial nerve crush injury. In our previous studies, ES was not initiated until 24 h after injury. The current experiment tested whether ES administered immediately following the crush injury would further decrease the time for complete recovery from facial paralysis. Rats received a unilateral facial nerve crush injury and an electrode was positioned on the nerve proximal to the crush site. Animals received daily 30 min sessions of ES for 1 d (day of injury only), 2 d, 4 d, 7 d, or daily until complete functional recovery. Untreated animals received no ES. Animals were observed daily for the return of facial function. Our findings demonstrated that one session of ES was as effective as daily stimulation at enhancing the recovery of most functional parameters. Therefore, the use of a single 30 min session of ES as a possible treatment strategy should be studied in human patients with paralysis as a result of acute nerve injuries.

Intrinsic and therapeutic factors determining the recovery of motor function after peripheral nerve transection.

Insufficient recovery after peripheral nerve injury has been attributed to (i) poor pathfinding of regrowing axons, (ii) excessive collateral axonal branching at the lesion site and (iii) polyneuronal innervation of the neuromuscular junctions (NMJ). The facial nerve transection model has been used initially to measure restoration of function after varying therapies and to examine the mechanisms underlying their effects. Since it is very difficult to control the navigation of several thousand axons, efforts concentrated on collateral branching and NMJ-polyinnervation. Treatment with antibodies against trophic factors to combat branching improved the precision of reinnervation, but had no positive effects on functional recovery. This suggested that polyneuronal reinnervation--rather than collateral branching--may be the critical limiting factor. The former could be reduced by pharmacological agents known to perturb microtubule assembly and was followed by recovery of function. Because muscle polyinnervation is activity-dependent and can be manipulated, attempts to design a clinically feasible therapy were performed by electrical stimulation or by soft tissue massage. Electrical stimulation applied to the transected facial nerve or to paralysed facial muscles did not improve vibrissal motor performance and failed to diminish polyinnervation. In contrast, gentle stroking of the paralysed muscles (vibrissal, orbicularis oculi, tongue musculature) resulted in full recovery of function. This manual stimulation was also effective after hypoglossal-facial nerve suture and after interpositional nerve grafting, but not after surgical reconstruction of the median nerve. All these findings raise hopes that clinically feasible and effective therapies could be soon designed and tested.

Poor functional recovery and muscle polyinnervation after facial nerve injury in fibroblast growth factor-2-/- mice can be improved by manual stimulation of denervated vibrissal muscles.

Functional recovery following facial nerve injury is poor. Adjacent neuromuscular junctions (NMJs) are "bridged" by terminal Schwann cells and numerous regenerating axonal sprouts. We have recently shown that manual stimulation (MS) restores whisking function and reduces polyinnervation of NMJs. Furthermore, MS requires both insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF). Here, we investigated whether fibroblast growth factor-2 (FGF-2) was also required for the beneficial effects of MS. Following transection and suture of the facial nerve (facial-facial anastomisis, FFA) in homozygous mice lacking FGF-2 (FGF-2(-/-)), vibrissal motor performance and the percentage of poly-innervated NMJ were quantified. In intact FGF-2(-/-) mice and their wildtype (WT) counterparts, there were no differences in amplitude of vibrissal whisking (about 50°) or in the percentage of polyinnervated NMJ (0%). After 2 months FFA and handling alone (i.e. no MS), the amplitude of vibrissal whisking in WT-mice decreased to 22±3°. In the FGF-2(-/-) mice, the amplitude was reduced further to 15±4°, that is, function was significantly poorer. Functional deficits were mirrored by increased polyinnervation of NMJ in WT mice (40.33±2.16%) with polyinnervation being increased further in FGF-2(-/-) mice (50.33±4.33%). However, regardless of the genotype, MS increased vibrissal whisking amplitude (WT: 33.9°±7.7; FGF-2(-/-): 33.4°±8.1) and concomitantly reduced polyinnervation (WT: 33.9%±7.7; FGF-2(-/-): 33.4%±8.1) to a similar extent. We conclude that, whereas lack of FGF-2 leads to poor functional recovery and target reinnervation, MS can nevertheless confer some functional benefit in its absence.

Subthreshold continuous electrical stimulation facilitates functional recovery of facial nerve after crush injury in rabbit.

We sought to determine whether electrical stimulation (ES) with subthreshold, continuous, low-frequency impulses is a viable clinical method for improving functional recovery after facial nerve crush injury. In 10 rabbits, bilateral crush injuries were made on the facial nerve by compression for 30 s with mosquito forceps, causing complete facial paralysis. Subthreshold continuous direct current ES with 20-Hz square-wave pulses was applied to the proximal stump on one side for 4 weeks. Vibrissae movement returned significantly earlier on the ES side, with a less variable recovery time. Electrophysiologically, the stimulated side had a significantly shorter latency, longer duration, and faster conduction velocity. Light and transmission electron microscopy revealed that the electrical stimulation also markedly decreased Wallerian degeneration. The average numbers of fluorescent, double-labeled nerve cells were significantly different between the ES and non-ES sides. This study shows that subthreshold, continuous, low-frequency ES immediately after a crush injury of the facial nerve results in earlier recovery of facial function and shorter overall recovery time.

Efficacy of functional training of the facial muscles for treatment of incomplete peripheral facial nerve injury.

OBJECTIVE: To investigate the efficacy of functional training of facial mimic muscles for patients with incomplete peripheral facial nerve injury. METHODS: Ninety-two patients with 241 injured branches of incomplete peripheral facial nerve injury were divided into a treatment group and a control group. The treatment group consisted of 58 cases that received functional training of facial mimic muscles. The rest of the cases served as controls. Assessment parameters included the House-Brackmann grading system, a quantitative facial nerve function estimating system and electroneurography. According to the three assessments, the facial nerve injury was divided into four grades: normal, minor, moderate and severe. The treatment group started training facial mimic muscle activity 2 weeks after facial nerve injury. After follow-ups of 1 to 4 years, the outcomes were statistically analysed. RESULTS: In the minor facial nerve injury group, there was no significant difference in the time needed for initial recovery (Ti, the time needed for significant recovery of the facial nerve function after injury) and final recovery (Tf, the time point after which no further improvement of facial nerve function was obtained) between the two groups (P > 0.05). No adverse effect was found in these cases. In the moderate facial nerve injury group, the Ti and Tf of the treatment group were shorter than those of the control group (P < 0.05). One case had synkinesis. In the patients with severe facial nerve injury, the recovery rate of facial nerve function in the treatment group was higher than that of the control group and the sequelae were less. CONCLUSION: Functional training of facial mimic muscles cannot shorten the time of recovery for the patients with minor facial nerve injury but it can speed up the recovery and reduce the undesirable sequelae such as synkinesis and hemifacial spasm for the patients with moderate and severe facial nerve injury.

Combinatorial treatments enhance recovery following facial nerve crush.

OBJECTIVES/HYPOTHESIS: To investigate the effects of various combinatorial treatments, consisting of a tapering dose of prednisone (P), a brief period of nerve electrical stimulation (ES), and systemic testosterone propionate (TP) on improving functional recovery following an intratemporal facial nerve crush injury. STUDY DESIGN: Prospective, controlled animal study. METHODS: After a right intratemporal facial nerve crush, adult male Sprague-Dawley rats were divided into the following eight treatment groups: 1) no treatment, 2) P only, 3) ES only, 4) ES + P, 5) TP only, 6) TP + P, 7) ES + TP, and 8) ES + TP + P. For each group n = 4-8. Recovery of the eyeblink reflex and vibrissae orientation and movement were assessed. Changes in peak amplitude and latency of evoked response, in response to facial nerve stimulation, was also recorded weekly. RESULTS: : Brief ES of the proximal nerve stump most effectively accelerated the initiation of functional recovery. Also, ES or TP treatments enhanced recovery of some functional parameters more than P treatment. When administered alone, none of the three treatments improved recovery of complete facial function. Only the combinatorial treatment of ES + TP, regardless of the presence of P, accelerated complete functional recovery and return of normal motor nerve conduction. CONCLUSIONS: Our findings suggest that a combinatorial treatment strategy of using brief ES and TP together promises to be an effective therapeutic intervention for promoting regeneration following facial nerve injury. Administration of P neither augments nor hinders recovery.

[Regeneration of the facial nerve in comparison to other peripheral nerves : from bench to bedside]. / Regeneration des N. facialis im Vergleich zu anderen peripheren Nerven : Aktuelles aus der Forschung für die Klinik.

Despite increasing knowledge of cellular and molecular mechanisms determining the success or failure of peripheral nerve regeneration, no effective treatments for peripheral nerve injury exist. Newly developed and validated approaches for precise numerical assessment of motor deficits have recently allowed testing of novel strategies in experimental animals. One of these approaches is the daily manual stimulation of the denervated musculature. This treatment is effective in cases of cranial nerve lesions with preservation of the sensory input (facial or hypoglossal nerve) and has the potential of direct translation in clinical settings. However, manual stimulation appears to be ineffective for the treatment of mixed peripheral nerve injuries. Generally, no long-term improvement of functional recovery is achieved by electrical stimulation in rodents. While short-term post-traumatic stimulation of the proximal nerve stump has no negative effects, direct electrical stimulation of the muscle during the period of de- and reinnervation appears to hinder muscle fibre reinnervation. Finally, experimental evidence suggests that application of peptides known as glycomimetics, which mimic functional properties of carbohydrate molecules, may provide significant benefits after injuries of mixed peripheral nerves.

Effects of hyperbaric oxygen therapy on facial nerve regeneration.

CONCLUSION: Hyperbaric oxygen treatment (HBOT) promoted an increase of the mean axonal diameter in the group evaluated 2 weeks after lesion induction, which suggests a more advanced regeneration process. However, the number of myelin nerve fibers of the facial nerve of the rabbits was similar when compared to the control and treatment groups, in both evaluation periods. OBJECTIVE: To evaluate the effect of HBOT on the histological pattern of the facial nerve in rabbits exposed to a nerve crush injury. MATERIALS AND METHODS: Twenty rabbits were exposed to facial nerve crush injury. Ten rabbits received HBOT, 10 rabbits comprised the control group. The rabbits were sacrificed 2 and 4 weeks after the trauma. Qualitative morphological analysis, measurement of the external axonal diameters and myelin fiber count were carried out in an area of 185 000 microm2. RESULTS: There was an increase in the area of the axons and thicker myelin in the 2 weeks treatment group in comparison with the control group. The mean diameter of the axons was of 2.34 microm in the control group and of 2.81 microm in the HBOT group, with statistically significant differences. The 2 week control group had a mean number of myelin fibers of 1865.2 +/- 664, and the HBOT group had a mean number of 2026.3 +/- 302; this was not statistically significant. The 4 week control group presented a mean of 2495.1 +/- 479 fibers and the HBOT group presented a mean of 2359.9 +/- 473; this was not statistically significant.

Accelerating functional recovery after rat facial nerve injury: Effects of gonadal steroids and electrical stimulation.

OBJECTIVE: We investigated the combined effects of electrical stimulation and testosterone propionate on overall recovery time in rats with extracranial crush injuries to the facial nerve. STUDY DESIGN: Male rats underwent castration 3 to 5 days prior to right facial nerve crush injury and electrode implantation. Rats were randomly assigned to two groups: crush injury + testosterone or crush injury with electrical stimulation + testosterone. Recovery was assessed by daily subjective examination documenting vibrissae orientation/movement, semi-eye blink, and full eye blink. RESULTS: Milestones of early recovery were noted to be significantly earlier in the groups with electrical stimulation, with/without testosterone. The addition of testosterone to electrical stimulation showed significant earlier return of late recovery parameters and complete overall recovery. CONCLUSION: Electrical stimulation may decrease cell death or promote sprouting to accelerate early recovery. Testosterone may affect the actual rate of axonal regeneration and produce acceleration in functional recovery. By targeting different stages of neural regeneration, the synergy of electrical stimulation and testosterone appears to have promise as a neurotherapeutic strategy for facial nerve injury.