Facial Nerve Regeneration In Rats Research Articles

The Effect of Rosuvastatin on Facial Nerve Regeneration After Facial Nerve Injury: An Experimental Animal Study.

Rosuvastatin is an antihyperlipidemic statin group pharmacological agent with antioxidant, neuroprotective, and anti-inflammatory effects. In this study, we aimed to examine the functional, electrophysiological, and histopathological effects of rosuvastatin or in combination with corticosteroids on facial nerve regeneration in rats with traumatic peripheral facial paralysis (PFP). PFP was induced in 28 female Sprague Dawley rats that we divided into 4 groups: group 1, control group; group 2, methylprednisolone group; group 3, rosuvastatin group; group 4, rosuvastatin and methylprednisolone group. Electrophysiological, functional, and histopathological examinations were performed before and after the medications. Electrophysiological threshold values of group 3 and group 4 were found to be significantly lower than the control group on day 21 after treatment (P = .002, P = .001; P < .01).In the histopathological evaluation, axonal degeneration, macrovacuolization, and vascular congestion levels were compared between the groups, and a statistically significant difference was observed in group 4 compared to the control group. The recovery time of the eye corneal reflex was found to be significantly higher in the control group than in groups 3 and 4 when comparing postoperative day 1 to day 7 and postoperative day 1 to day 14. Rosuvastatin, especially when combined with methylprednisolone was found to significantly increase the facial nerve electrophysiological, functional, and histopathological recovery in injury-induced traumatic PFP.

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

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

Comparison of the effects of methylprednisolone, hyperbaric oxygen and hesperidin + diosmin on the facial nerve injury: an experimental animal model

Background Necessity of new and alternative treatments in traumatic facial nerve injury. Aims/Objective In this experimental study, we aimed to evaluate the histopathologic and functional effects of methylprednisolone, hyperbaric oxygen and hesperidin + diosmin treatments on traumatic facial nerve regeneration in rats. Methods After facial nerve injury, five groups were formed with eight rats in each group: Group 1 (negative control), 2 (operation), 3 (corticosteroid), 4 (hyperbaric oxygen), 5 (hesperidin + diosmin). Blink reflex of rats evaluated a day after the operation and at the first, second and third weeks. Facial nerve samples from sacrificed animals were examined under a light microscope. Results According to our results, in group 4; axonal degeneration and vascular congestion were significantly lower than group 2 and 3, and myelin sheath thickness was significantly higher than group 3. In group 5; axonal degeneration was significantly lower than group 2 and vascular congestion was significantly lower than group 2 and 3. In terms of functional recovery; there was no statistically significant difference between the groups. Conclusions and significance It has been shown that both hyperbaric oxygen and hesperidin + diosmin treatments have positive effects on facial nerve regeneration. Both treatments may be good alternatives for ameliorating traumatic nerve injury, but these treatment modalities need to be further explored.

Effect of Bumetanide on Facial Nerve Regeneration in Rat Model.

We investigated the effects of bumetanide alone and in combination with dexamethasone on facial nerve regeneration in rats with facial paralysis. A prospective controlled animal study. An animal laboratory. Facial paralysis was induced in 32 Wistar rats that we then divided into 4 groups: group 1, control; group 2, bumetanide; group 3, dexamethasone; group 4, bumetanide and dexamethasone. Electroneurography was performed 1, 2, and 4 weeks later, and nerve regeneration was evaluated by electron and light microscopy and Western blotting in week 4. Regarding the comparison between preoperative values and week 4, the latency difference in group 1 (1.25 milliseconds) was significantly higher than those of groups 2 to 4 (0.56, 0.34, and 0.10 milliseconds, respectively; P = .001). The latency increment in groups 2 and 3 was higher than that of group 4 (P = .002 and P = .046) in week 4, whereas groups 2 and 3 did not differ significantly (P = .291). Amplitude difference was not statistically significant from week 4 among all groups (all P > .05). The number of myelinated axons was significantly higher in all treatment groups than in the control group (P = .001). Axon number and intensity were significantly higher in group 4 as compared with groups 2 and 3 (P = .009, P = .005). After primary neurorrhaphy, dexamethasone and bumetanide alone promoted nerve recovery based on electrophysiologic and histologic measures. Combination therapy was, however, superior.

Neural Crest Stem-Like Cells Non-genetically Induced from Human Gingiva-Derived Mesenchymal Stem Cells Promote Facial Nerve Regeneration in Rats.

Non-genetic induction of somatic cells into neural crest stem-like cells (NCSCs) is promising for potential cell-based therapies for post-traumatic peripheral nerve regeneration. Here, we report that human gingiva-derived mesenchymal stem cells (GMSCs) could be reproducibly and readily induced into NCSCs via non-genetic approaches. Compared to parental GMSCs, induced NCSC population had increased expression in NCSC-related genes and displayed robust differentiation into neuronal and Schwann-like cells. Knockdown of the expression of Yes-associated protein 1 (YAP1), a critical mechanosensor and mechanotransducer, attenuated the expression of NCSC-related genes; specific blocking of RhoA/ROCK activity and non-muscle myosin II (NM II)-dependent contraction suppressed YAP1 and NCSC-related genes and concurrently abolished neural spheroid formation in NCSCs. Using a rat model of facial nerve defect, implantation of NCSC-laden nerve conduits promoted functional regeneration of the injured nerve. These promising findings demonstrate that induced NCSCs derived from GMSCs represent an easily accessible and promising source of neural stem-like cells for peripheral nerve regeneration.

Experimental role of cervical sympathetic block during facial nerve injury and regeneration in rats

To explore the effects of cervical sympathetic block (CSB) on facial nerve regeneration in rats and seek the optimal timing of treatment. A total of 72 adult Sprague-Dawley rats were divided randomly into 4 groups of sham-operation (sham), model control (NS), CSB1 and CSB2 (n = 18 each). Except for sham group, the model of peripheral facial paralysis was established for three other groups. After treating facial nerves injury with CSB at different timepoints, the behavioral changes of rats were observed.Electroneurography (ENoG) of injured nerves was performed and the expressions of glial cell derived neurotrophic factor (GDNF) of facial nerve nucleus were detected at different stages. The facial whisker movement function scores in sham, NS, CSB1 and CSB2 groups were 3.87 ± 0.35, 0.50 ± 0.52, 1.07 ± 0.62 and 0.81 ± 0.42 (F = 2.934, P = 0.035) at Day 7, 3.85 ± 0.37, 0.91 ± 0.52, 1.57 ± 0.65 and 1.07 ± 0.62 (F = 2.537, P = 0.038) at Day 14 and 3.85 ± 0.37, 1.71 ± 0.47, 3.00 ± 0.68 and 2.36 ± 0.49 (F = 3.627, P = 0.024) at Day 28. At Day 7, LatSD and AmpSD were not detected in NS, CSB1 and CSB2 groups.However, at Day 14, the values of LatSD were (1.26 ± 0.19), (6.67 ± 0.36), (4.67 ± 0.36) and (6.17 ± 0.36) ms, showing a significant difference (F = 3.052, P = 0.024) and AmpSD (6.42 ± 1.93), (2.16 ± 1.87), (4.16 ± 1.80) and (3.66 ± 1.40) mv, also a significance (F = 3.634, P = 0.021). And at Day 28, LatSD were (1.31 ± 0.17), (3.17 ± 0.19), (1.93 ± 0.12) and (2.60 ± 0.22) ms (F = 2.729, P = 0.032) and AmpSD (6.82 ± 2.30), (4.72 ± 5.23), (6.22 ± 3.50) and (5.82 ± 4.10) mv (F = 3.827, P = 0.019). The expression quantities of GDNF in 4 groups produced significant differences at Day 7 (4.67 ± 0.81, 13.52 ± 0.58, 26.17 ± 1.01 and 14.86 ± 1.03, F = 3.637, P = 0.028), Day 14 (5.67 ± 0.57, 24.41 ± 2.86, 26.52 ± 1.36 and 25.48 ± 1.42, F = 2.946, P = 0.031) and Day 28 (5.37 ± 0.92, 26.64 ± 1.68, 27.38 ± 1.66 and 25.69 ± 1.99, F = 4.273, P = 0.012). During early stage of facial nerve injury, the treatment of CSB may increase the expression of GDNF of facial nerve nucleus at early stage and thus accelerate the recovery of facial nerve injury in rats.

Rat whisker movement after facial nerve lesion: Evidence for autonomic contraction of skeletal muscle

Vibrissal whisking is often employed to track facial nerve regeneration in rats; however, we have observed similar degrees of whisking recovery after facial nerve transection with or without repair. We hypothesized that the source of non-facial nerve-mediated whisker movement after chronic denervation was from autonomic, cholinergic axons traveling within the infraorbital branch of the trigeminal nerve (ION). Rats underwent unilateral facial nerve transection with repair (N=7) or resection without repair (N=11). Post-operative whisking amplitude was measured weekly across 10weeks, and during intraoperative stimulation of the ION and facial nerves at ⩾18weeks. Whisking was also measured after subsequent ION transection (N=6) or pharmacologic blocking of the autonomic ganglia using hexamethonium (N=3), and after snout cooling intended to elicit a vasodilation reflex (N=3). Whisking recovered more quickly and with greater amplitude in rats that underwent facial nerve repair compared to resection (P<0.05), but individual rats overlapped in whisking amplitude across both groups. In the resected rats, non-facial-nerve-mediated whisking was elicited by electrical stimulation of the ION, temporarily diminished following hexamethonium injection, abolished by transection of the ION, and rapidly and significantly (P<0.05) increased by snout cooling. Moreover, fibrillation-related whisker movements decreased in all rats during the initial recovery period (indicative of reinnervation), but re-appeared in the resected rats after undergoing ION transection (indicative of motor denervation). Cholinergic, parasympathetic axons traveling within the ION innervate whisker pad vasculature, and immunohistochemistry for vasoactive intestinal peptide revealed these axons branching extensively over whisker pad muscles and contacting neuromuscular junctions after facial nerve resection. This study provides the first behavioral and anatomical evidence of spontaneous autonomic innervation of skeletal muscle after motor nerve lesion, which not only has implications for interpreting facial nerve reinnervation results, but also calls into question whether autonomic-mediated innervation of striated muscle occurs naturally in other forms of neuropathy.

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

ObjectiveThe 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 methodsAfter 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. ResultsThere 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. ConclusionThe 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.

Assessment of a Neurophysiological Model of the Mandibular Branch of the Facial Nerve in Rats by Electromyography

Our objective was to develop an experimental model for the noninvasive and objective evaluation of facial nerve regeneration in rats using a motor nerve conduction test (electromyography). Twenty-two rats were submitted to neurophysiological evaluation using motor nerve conduction of the mandibular branch of the facial nerve to obtain the compound muscle action potentials (CMAPs). To record the CMAPs, we used two needle electrodes that were inserted into the lower lip muscle of the rat. A supramaximal electrical stimulus was applied, and the values of CMAP latency, amplitude, length, area, and stimulus intensity obtained from each side were compared by use of the Wilcoxon test. There was no significant difference (all p > 0.05) in latency, amplitude, duration, area, or intensity of stimuli between the two sides. The amplitudes ranged between 1.61 and 8.30 mV, the latencies between 1.03 and 1.97 ms, and the stimulus intensities between 1.50 and 2.90 mA. This is a noninvasive, easy, and highly reproducible method that contributes to an improvement of the techniques previously described and may contribute to future studies of the degeneration and regeneration of the facial nerve.

Combined use of decellularized allogeneic artery conduits with autologous transdifferentiated adipose-derived stem cells for facial nerve regeneration in rats

Natural biological conduits containing seed cells have been widely used as an alternative strategy for nerve gap reconstruction to replace traditional nerve autograft techniques. The purpose of this study was to investigate the effects of a decellularized allogeneic artery conduit containing autologous transdifferentiated adipose-derived stem cells (dADSCs) on an 8-mm facial nerve branch lesion in a rat model. After 8 weeks, functional evaluation of vibrissae movements and electrophysiological assessment, retrograde labeling of facial motoneurons and morphological analysis of regenerated nerves were performed to assess nerve regeneration. The transected nerves reconstructed with dADSC-seeded artery conduits achieved satisfying regenerative outcomes associated with morphological and functional improvements which approached those achieved with Schwann cell (SC)-seeded artery conduits, and superior to those achieved with artery conduits alone or ADSC-seeded artery conduits, but inferior to those achieved with nerve autografts. Besides, numerous transplanted PKH26-labeled dADSCs maintained their acquired SC-phenotype and myelin sheath-forming capacity inside decellularized artery conduits and were involved in the process of axonal regeneration and remyelination. Collectively, our combined use of decellularized allogeneic artery conduits with autologous dADSCs certainly showed beneficial effects on nerve regeneration and functional restoration, and thus represents an alternative approach for the reconstruction of peripheral facial nerve defects.

PLGA artificial nerve conduits with dental pulp cells promote facial nerve regeneration

A number of recent studies have shown the effectiveness of tubulation, using neural progenitor cells or Schwann cells, for promoting nerve regeneration. However, the use of neural cells from other neural donor tissues has potentially serious clinical complications. Therefore, we focused on dental pulp as a new cell source for use in such artificial conditions. Previously, we showed that silicone tubes filled with dental pulp cells (DPCs) promoted facial nerve regeneration in rats. However, the use of silicone tubes requires a secondary removal operation because they may give rise to chronic inflammation and pain. Therefore, to avoid this procedure, a new artificial device was prepared from a degradable poly-DL-lactide-co-glycolide (PLGA) tube containing DPCs, and its effectiveness for repairing gaps in the facial nerves of rats was investigated. A PLGA tube containing rat DPCs embedded in a collagen gel was transplanted into a gap in a rat facial nerve. Five days after transplantation, the facial nerves connected by the PLGA tubes containing DPCs were repaired more quickly than the control nerves. The PLGA tubes were resorbed in vivo and nerve regeneration was observed 2 months after the transplantation. Immunostaining showed that Tuj1-positive axons were present in the regenerated nerves 2 months after transplantation, and osmium-toluidine blue staining showed no mineralization of the regenerated nerves in those tubes containing myelinated fibres after 9 weeks. PLGA tubes filled with DPCs promoted nerve regeneration and were readily resorbed in vivo.

Influência do AMP cíclico na regeneração do nervo facial em ratos

Estimular a regeneração do nervo facial é ainda hoje um desafio. OBJETIVO: Estudar a possível influência neurotrófica do nucleotídeo cíclico adenosina monofosfato (AMPc) na regeneração do nervo facial de ratos Wistar. MÉTODO: Trinta e dois animais foram submetidos à transecção completa com sutura imediata do nervo facial direito, sendo divididos em expostos ou não expostos à aplicação tópica de AMPc, com análises comportamentais (movimentação de vibrissas e fechamento da rima palpebral) e histométrica (contagem de fibras mielinizadas) em dois períodos, 14 e 28 dias após a lesão. RESULTADO: Encontramos diferenças estatísticas (p&lt;0,05) nas análises comportamental e histométrica no 14º dia, sugerindo uma precocidade na regeneração do nervo facial exposto ao AMPc. CONCLUSÃO: Nosso estudo constatou uma possível ação neurotrófica do AMPc na regeneração do nervo facial em ratos.

Influence of cyclic AMP on facial nerve regeneration in rats

SummaryPromoting facial nerve regeneration is a significant challenge.AimTo evaluate the possible neurotrophic influence of cyclic AMP on facial nerve regeneration of Wistar rats.MethodThe right facial nerve of thirty-two animals were completely transected and immediately sutured, followed by exposure or not to topical cyclic AMP. Behavioral and histometric analyses were done at 14 and 28 days.ResultsStatistical differences (p<0.05) were found in the behavioral and histometric analyses on the 14th day, suggesting an early regenerative response of the facial nerve to cAMP exposure.ConclusionThis study demonstrates a possible neurotrophic effect of cAMP on facial nerve regeneration in rats.

Tubulation with Dental Pulp Cells Promotes Facial Nerve Regeneration in Rats

Dental pulp is an easily obtainable source of viable cells for potential use in peripheral nerve regeneration. We prepared artificial conditions for nerve regeneration using a silicone tube containing a collagen gel embedded with rat dental pulp cells, and we examined its effectiveness for repairing a gap in the rat facial nerve. Twelve days after transplantation, defective facial nerves connected with silicone tubes containing dental pulp cells were repaired more rapidly than control tubes containing the collagen gel alone. When a tube containing green fluorescent protein (GFP)-positive dental pulp cells was transplanted into a facial nerve gap in a GFP-negative rat, we observed regenerated nerves with GFP-positive cells at 2 weeks posttransplantation. The regenerated nerves included Tuj1-positive axons, RECA1 and GFP double-positive blood vessels, and S100 and GFP double-positive Schwann-like supportive cells. Osmium-toluidine blue staining revealed that the regenerated nerves contained myelinated fibers. Moreover, fluorescent retrograde tracing analysis by application of Fluoro-Gold into the regenerated nerves demonstrated the presence of Fluoro-Gold-positive motor neurons in the facial nucleus of the rat brain. These results suggest that the transplanted dental pulp cells formed blood vessels and myelinating tissue and contributed to the promotion of normal nerve regeneration.

Modelo experimental comportamental e histológico da regeneração do nervo facial em ratos

O estabelecimento de modelos experimentais é o passo inicial para estudos de regeneração neural. OBJETIVO: Estabelecer modelo experimental de regeneração do nervo facial. MATERIAIS E MÉTODOS: Ratos Wistar com secção completa e sutura do tronco do nervo facial extratemporal, com análise comportamental e histológica até 9 semanas. FORMA DE ESTUDO: Estudo prospectivo experimental. RESULTADOS: Progressiva recuperação clínica e histológica dos animais. CONCLUSÃO: Estabelecemos um método aceitável para o estudo de regeneração do nervo facial em ratos.

Behavioral and histologic experimental model of facial nerve regeneration in rats

To setup an experimental model is the first step to study neural regeneration. Setting up an experimental model on facial nerve regeneration. Wistar rats with complete sectioning and suturing of the extratemporal facial nerve trunk; with a behavioral and histological analysis for 9 weeks. Experimental prospective study. Progressive clinical and histological recovery of the animals. Our method is acceptable to study facial nerve regeneration in rats.