Facial Nerve Avulsion Research Articles

Neuroprotective effects of pregabalin in a rat model of intracisternal facial nerve avulsion.

Pregabalin (PGB), a drug used for treating neuropathic pain, has immune-modulating property that may have therapeutic implications. Suppression of microglial activation and improvement in functional recovery was observed in experimental spinal cord injury after PGB administration. An experimental study was conducted to evaluate whether PGB could afford neuroprotection in a rat model of intracisternal facial nerve avulsion. Twenty-eight male Wistar rats (250-300 g) were dichotomized into two groups: a PGB group (N.=14) and a control group (N.=14). The PGB group received a total of 4 intraperitoneal PGB injections (30 mg/kg, 15 minutes preoperatively and 4, 24, and 48 hours postoperatively), and the control group underwent intraperitoneal saline injection. Intracisternal facial nerve avulsion was created by tangential pull-out of the nerve surgically exposed at the stylomastoid foramen. In both groups, the brainstem containing the facial motor nuclei neurons was thin-sliced and stained with cresyl violet, and the number of viable neurons in the facial motor nuclei on days 14 and 28 was counted under microscope. The total viable neuron count was significantly greater in the PGB group than in the Control group both on day 14 (271.4±14.9 vs. 196.2±22.2, P<0.01) and day 28 (160.2±21.6 vs. 102.6±13.4, P<0.01). Furthermore, CD11b/c immunostaining on days 3 and 8 showed that CD11b/c-positive cells, suggestive of activated microglia, were observed only in the control group. Better neuronal survival by PGB administration may be beneficial and clinically relevant when surgical reconstruction of the facial nerve, such as hypoglossal-facial nerve anastomosis, is considered.

Involvement of activated microglia in increased vulnerability of motoneurons after facial nerve avulsion in presymptomatic amyotrophic lateral sclerosis model rats

Activated microglia are observed in various neurodegenerative diseases and are thought to be involved in the processes of neuronal cell death. Motoneuron damage in the facial nuclei after facial nerve avulsion is accelerated in presymptomatic transgenic rats expressing human mutant Cu(2+) /Zn(2+) superoxide dismutase 1 (SOD1), compared with that in wild-type rats. To reveal the functional role of microglia in motoneuronal death, we investigated the microglial response after facial nerve avulsion in presymptomatic mutant SOD1(H46R) (mSOD1(H46R) ) rats. At 3 days after avulsion, microglial clusters were observed in the facial nuclei of both wild-type and mSOD1(H46R) rats. The numbers of microglial clusters, proliferating microglia, and microglial attachments to motoneurons were significantly higher in mSOD1(H46R) rats, compared with those in wild-type rats. Immunopositive signals for the phagocytic marker ED1 were significantly stronger in mSOD1(H46R) rats, compared with that in wild-type rats, at 2 weeks after avulsion. Furthermore, primary microglia prepared from mSOD1(H46R) rats showed enhanced phagocytic activity, compared with that in wild-type rats. The expression of P2Y(12) mRNA was higher in the facial nuclei of mSOD1(H46R) rats, compared with that in wild-type rats. A laser microdissection system revealed that the expression of ATF3 mRNA was higher in the motoneurons of mSOD1(H46R) rats, compared with that in wild-type rats, at 2 days after avulsion. These results indicate that microglial activation in response to early neuronal damage increased in mSOD1(H46R) rats and suggest that the enhanced activation of microglia may lead to an increase in the vulnerability of motoneurons after avulsion in mSOD1(H46R) rats.

Morphological changes of Golgi apparatus in adult rats after facial nerve injuries

We examined the morphological changes of Golgi apparatus (GA) of the facial motor neurons in rats after facial nerve avulsion or axotomy. In rats after avulsion, the numbers of motor neurons showed reduction and fragmentation of GA, namely the organelle lost the normal network-like configuration which was replaced by numerous small disconnected elements (fine fragmentation). This GA fragmentation was morphologically indistinguishable from that previously reported in amyotrophic lateral sclerosis (ALS). On the other hand, axotomy did not induce significant motor neuron loss, and the GA had lost the elongated profiles (coarse fragmentation). These results suggest that there may be a similar cascade leading to motor neuron death in rats after avulsion, and ALS and GA observed in rats after axotomy may not be related to neuronal death.

Facial and Vestibulocochlear Nerve Avulsion at the Fundus of the Internal Auditory Canal in a Child Without a Temporal Bone Fracture

To describe a case of facial, vestibular, and cochlear nerve avulsion secondary to blunt trauma without an associated temporal bone fracture. Clinical capsule report. University hospital. A 3.5-year-old girl presented with immediate facial nerve paralysis and complete deafness after being struck by an automobile. High-resolution computed tomography demonstrated a depressed occipital bone fracture with no visible fracture of the temporal bone. Magnetic resonance imaging sequence raised the question of VIIth nerve bundle discontinuity at the distal end of the internal auditory canal. The patient underwent a posterior fossa craniotomy via a translabyrinthine approach 9 months after the initial injury, and facial and auditory nerve avulsion at the fundus was confirmed at the time of surgery. The proximal segment of the facial nerve had formed a traumatic neuroma, which was resected, and primarily anastomosed to the rerouted distal segment. Facial nerve function. Patient has regained facial function to Grade III/VI House-Brackmann with no asymmetry at rest. An unusual pattern of injury is described. We suggest that in patients presenting with facial nerve paralysis secondary to blunt trauma, without an associated temporal bone fracture, high-resolution magnetic resonance imaging is recommended to evaluate internal auditory canal discontinuity of the VIIth and VIIIth nerve complexes. A potential mechanism of avulsion is explained.

Involvement of phagocytic microglia in increased vulnerability of motoneurons after facial nerve avulsion in presymptomatic ALS model rats

Involvement of phagocytic microglia in increased vulnerability of motoneurons after facial nerve avulsion in presymptomatic ALS model rats

Neuroprotective effects of vitamin E on adult rat motor neurones following facial nerve avulsion

Conclusion. The present study demonstrates the neuroprotective effect of vitamin E after peripheral facial nerve injury. Antioxidants may have therapeutic potential in traumatic facial nerve dysfunction resulting from traumatic temporal bone injury and ear surgery. Objective. We investigated the possible neuroprotective effect of vitamin E on the facial motor nucleus (FMN) motor neurones after peripheral nerve avulsion. Methods. In 36 adult rats, the right facial nerve was avulsed from the stylomastoid foramen. Following nerve avulsion, immunohistochemistry was used to investigate the effects of vitamin E on 4-hydroxynonenal (HNE) activity. FMN motor neurones and glial cells were counted bilaterally in sections stained with cresyl violet. Results. Rats administered vitamin E exhibited clear suppression of injury-induced neuronal HNE expression in the ipsilateral FMN as compared to non-treated controls. Following nerve avulsion, the number of surviving motor neurones in the ipsilateral FMN was significantly greater among vitamin E-treated rats than non-treated controls.

Relationship between ribosomal RNA gene transcription activity and motoneuron death: Observations of avulsion and axotomy of the facial nerve in rats

Motoneuron number and expression of cytoplasmic RNA and ribosomal RNA (rRNA) gene transcription activity in the facial nucleus were examined quantitatively and chronologically for up to 4 weeks in rats after facial nerve axotomy and avulsion in order to elucidate interrelationships in axonal changes. The right facial nerves of adult Fischer rats were avulsed at a portion of the outlet or axotomized at a portion of the foramen stylomastoideus. The number of large motoneurons in the facial nucleus was reduced by 40% 2 weeks after avulsion and by 70% 4 weeks after avulsion but displayed a 19% loss even 4 weeks after axotomy. The amount of cytoplasmic RNA decreased significantly and progressively from 1 day after avulsion. rRNA gene transcription activity in the large motoneurons of the facial nucleus decreased significantly beginning 30 min after both axotomy and avulsion, but the severity of the decrease was far more marked in the avulsion group, showing a 59% loss from the control value 4 weeks after avulsion. These findings indicate that rRNA gene transcription activity, expression of cytoplasmic RNA, and the number of motoneurons that survive are interrelated and that the decrease in rRNA gene transcription activity is a very early event in the phenomena observed in the axonal reactions of motoneurons.

Bax‐dependent and ‐independent death of motoneurons after facial nerve injury in adult mice

Nerve injury-induced neuronal death may occur after accidental trauma or nerve inflammation. Although the response to facial root avulsion has been examined in rodent models, there are conflicting results as to whether motoneuron (MN) death is mediated by apoptosis or necrosis. We examined the response of MNs and proximal nerves after facial nerve avulsion in adult mice. Following facial nerve avulsion in 4-5-week-old mice, we observed a progressive reduction of MNs such that by 4 weeks less than 10% of avulsed MNs remained compared with the control side. The profile of MN degeneration was distinct from axotomy-induced responses. For example, the onset of MN death was more rapid, and the extent of MN loss was greater compared with axotomy. Furthermore, the degeneration of oligodendrocytes and the activation of microglia were increased in the proximal nerve after avulsion. Ultrastructural observations suggested that root avulsion mainly induces non-apoptotic neuronal death, although a small subset of neurons appeared to die via apoptosis. To evaluate the contribution of apoptotic death, we evaluated MN responses in Bax-knockout (KO) mice in which neurons are rescued from apoptotic death. Surprisingly, although the majority of Bax-KO mice exhibited only a moderate MN loss after avulsion, a subset of Bax-KO mice (25%) exhibited extensive MN death and injury-induced changes in the nerve that were indistinguishable from events in wild-type littermates. These results suggest that both Bax-dependent and -independent forms of cell death are evoked by root avulsion, and that programmed cell death may be involved in triggering a robust necrotic response.

Astrocyte-derived transgene GDNF promotes complete and long-term survival of adult facial motoneurons following avulsion and differentially regulates the expression of transcription factors of AP-1 and ATF/CREB families

Glial-cell-line-derived neurotrophic factor (GDNF) is a potent survival factor for motoneurons (MNs). We have previously demonstrated that overexpression of GDNF in astrocytes of GFAP-GDNF mice promotes long-term survival of neonatal MNs after facial nerve axotomy. In the present study, we investigated whether astrocyte-derived GDNF could also have a neuroprotective effect on adult MNs following facial nerve avulsion. We also examined avulsion- and GDNF-induced changes in the expression pattern of several members of the AP-1 and ATF/CREB families of transcription factors, which are involved in the fate determination of neurons following injury. We demonstrated that GDNF promotes complete rescue of avulsed MNs for at least 4 months post-injury. Transgene GDNF significantly upregulates c-Jun expression in naive MNs, further upregulates injury-induced c-Jun expression in facial MNs, and results in its activation in most surviving MNs. No significant changes were found in c-Fos expression. We found that GDNF has an opposing effect on ATF2 and ATF3 expression. It dramatically downregulates increased levels of ATF3 in response to injury, whereas the expression of ATF2, which is normally reduced after injury, is completely preserved in GFAP-GDNF mice. Our data suggest that maintenance of high levels of ATF2 in injured MNs could be crucial in modulating c-Jun function, and c-Jun/ATF2 signaling could be involved in GDNF-mediated survival of mature MNs.

Motoneuron degeneration after facial nerve avulsion is exacerbated in presymptomatic transgenic rats expressing human mutant Cu/Zn superoxide dismutase

We investigated motoneuron degeneration after proximal nerve injury in presymptomatic transgenic (tg) rats expressing human mutant Cu/Zn superoxide dismutase (SOD1). The right facial nerves of presymptomatic tg rats expressing human H46R or G93A SOD1 and their non-tg littermates were avulsed, and facial nuclei were examined at 2 weeks postoperation. Nissl-stained cell counts revealed that facial motoneuron loss after avulsion was exacerbated in H46R- and G93A-tg rats compared with their non-tg littermates. The loss of motoneurons in G93A-tg rats after avulsion was significantly greater than that in H46R-tg rats. Intense cytoplasmic immunolabeling for SOD1 in injured motoneurons after avulsion was demonstrated in H46R- and G93A-tg rats but not in their littermates. Facial axotomy did not induce significant motoneuron loss nor enhance SOD1 immunoreactivity in these tg rats and non-tg littermates at 2 weeks postoperation, although both axotomy and avulsion elicited intense immunolabeling for activating transcription factor-3, phosphorylated c-Jun, and phosphorylated heat shock protein 27 in injured motoneurons of all these animals. The present data indicate the increased vulnerability of injured motoneurons after avulsion in the presymptomatic mutant SOD1-tg rats.

Different levels of neuroprotection by two insulin-like growth factor-I splice variants

We compared the neuroprotective effects of a liver-type isoform of insulin-like growth factor-I (IGF-IEa) and its splice variant, mechano-growth factor (MGF), isolated from active skeletal muscle. cDNAs of these peptides were injected into the facial muscle of adult rats prior to facial nerve avulsion. This resulted in significant neuroprotection of 88% and 37%, respectively, of motoneurons compared to control plasmid and avulsion-only groups. MGF is markedly more effective than the liver-type, systemic IGF-I for motoneuron survival, suggesting a major role for the peripheral target in adult neuronal maintenance and survival.

Oral administration of a neuroprotective compound T‐588 prevents motoneuron degeneration after facial nerve avulsion in adult rats

R(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino) ethoxylethanol hydrochloride (T-588), a synthetic compound, has been shown to have neuroprotective potentials for neuronal cells. We investigated whether orally administered T-588 can rescue injured motoneurons after facial nerve avulsion in adult rats. The right facial nerves of adult Fischer 344 male rats were avulsed and the animals were freely administered solution of 0.05% (w/v) T-588 or received T-588 (3-30 mg/kg/day) through an oral tube for 1-4 weeks. Facial motoneurons on both sides of the facial nuclei were counted in Nissl-stained sections, and choline acetyltransferase (ChAT) immunoreactivity in injured motoneurons and ChAT enzyme activities in the ventral brain stem tissue containing the facial nuclei were examined. Both free oral administration of 0.05% T-588 solution and oral tube administration of T-588 (30mg/kg/day) improved the survival of facial motoneurons at 3 or 4 weeks after avulsion. These treatments ameliorated ChAT immunoreactivity in injured motoneurons and the tissue ChAT enzyme activities at 1-week postoperation examined. These results indicate that oral administration of T-588 ameliorates the survival of injured motoneurons and supports their neuronal function after facial nerve avulsion in adult rats. T-588 may have therapeutic potential in motoneuron injury or motor neuron diseases in humans.

Oral administration of a neuroprotective compound T-588 prevents motoneuron degeneration after facial nerve avulsion in adult rats

Oral administration of a neuroprotective compound T-588 prevents motoneuron degeneration after facial nerve avulsion in adult rats

Age, diet and injury affect the survival of facial motoneurons

Using the model of facial nerve avulsion, we have compared the effects of injury, age and diet on motoneuronal survival. One to four weeks after nerve avulsion, 50–75% motoneuron loss was quantified in ad libitum-fed rats aged 7 days (neonate), 6 months (adult) and 24 months (aging) at the time of injury. Evidence of apoptosis was found for neonatal rats at 3 days post-injury, but not for neonates examined 7 days or adult or aging rats examined 1 month after injury. Non-operated, ad libitum-fed rats showed no significant loss of facial motoneurons by 24 months. Surprisingly, non-operated rats whose food intake was restricted to 15 g standard rat chow per day from the age of 6 months lost 50% of their motoneurons by 24 months. Facial nerve avulsion of 24-month-old rats raised on this restricted diet did not result in any additional loss of motoneurons one month after injury. These results challenge the common view that aging results in neuronal loss and that dietary restriction is universally beneficial.

Adenoviral gene transfer of GDNF, BDNF and TGF beta 2, but not CNTF, cardiotrophin-1 or IGF1, protects injured adult motoneurons after facial nerve avulsion.

We examined neuroprotective effects of recombinant adenoviral vectors encoding glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT1), insulin-like growth factor-1 (IGF1), and transforming growth factor-beta2 (TGFbeta2) on lesioned adult rat facial motoneurons. The right facial nerves of adult Fischer 344 male rats were avulsed and removed from the stylomastoid foramen, and adenoviral vectors were injected into the facial canal. Animals avulsed and treated with adenovirus encoding GDNF, BDNF, CNTF, CT1, IGF1 and TGFbeta2 showed intense immunolabeling for these factors in lesioned facial motoneurons, respectively, indicating adenoviral induction of the neurotrophic factors in these neurons. The treatment with adenovirus encoding GDNF, BDNF, or TGFbeta2 after avulsion significantly prevented the loss of lesioned facial motoneurons, improved choline acetyltransferase immunoreactivity and prevented the induction of nitric oxide synthase activity in these neurons. The treatment with adenovirus encoding CNTF, CT1 or IGF1, however, failed to protect these neurons after avulsion. These results indicate that the gene transfer of GDNF and BDNF and TGFbeta2 but not CNTF, CT1 or IGF1 may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.

Rapid estimates of neuron number in the confocal microscope combined with in situ hybridisation and immunocytochemistry

A rapid counting protocol is described which combines the optical disector and Cavalieri methods on non-embedded slices of fixed tissue viewed in the confocal laser scanning microscope. By eliminating the embedding stage and avoiding the need to align adjacent sections in the z plane for counting, considerable time savings are gained over physical disector methods. It also allows the remaining non-embedded sections to be used for other purposes, such as in situ hybridisation and immunocytochemistry. Starting with fixed brainstem, it was possible in less than 2 h to determine the total number of motoneurons in both facial nuclei of an adult Sprague–Dawley rat. This method revealed that the normal facial nucleus contained approximately 3200 motoneurons ( n=12 rats). One month following facial nerve avulsion ( n=4 rats), mean numbers of motoneurons were reduced by 75%. Using intervening sections, changes in neuronal number were compared with changes in in situ hybridisation signal and immunostaining.

Adenoviral vector-mediated GDNF gene transfer prevents death of adult facial motoneurons.

We examined neuroprotective effects of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the lesioned adult rat facial motoneurons. After facial nerve avulsion, animals locally injected into the facial canal with AxCALacZ (adenovirus encoding beta-galactosidase gene) or AxCAhGDNF showed expression of beta-galactosidase activity or intense immunolabeling for GDNF in lesioned facial motoneurons, respectively. The treatment with AxCAhGDNF after avulsion significantly prevented the loss of lesioned facial motoneurons, ameliorated choline acetyltransferase immunoreactivity, and suppressed the activity of nitric oxide synthase in these neurons. These results indicate that the adenovirus-mediated gene transfer of GDNF may prevent the degeneration of motoneurons in adult humans with peripheral nerve injury and motor neuron diseases.

The role of nitric oxide in facial motoneuronal death

The present study aimed to determine whether nitric oxide synthase (NOS)/nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity would be induced in facial motoneurons after facial nerve avulsion and if so, whether such activity was related to neuronal death commonly observed after such injury. The left facial nerve in each of 28 Wistar albino rats was avulsed from the facial canal. Ten of them received either daily injections of N ω-nitro- l-arginine methyl ether ( l-NAME) or the vehicle. After survival times ranging from 2–50 days, serial brainstem sections were processed for NOS immunocytochemistry and NADPH-d histochemistry respectively. The number of surviving, NOS and NADPH-d positive and NOS negative neurons were compared statistically. Two days after facial nerve avulsion, increased NADPH-d activity was noticed in the facial motoneurons and in the endothelial lining of many dilated blood vessels in the facial motor nucleus (FMN). NOS-positive neurons were not detectable until five days after operation. Both the number and staining intensity of NADPH-d and NOS-positive neurons increased steadily with increasing survival time while the number of surviving neurons decreased after nerve avulsion. Daily administration of l-NAME protected 17% the neurons from death in the affected FMN when examined at 30 days after nerve avulsion, suggesting a neurodestructive property of NO. It was also noticed that some of the surviving neurons were first NOS positive but became NOS negative later.

Surgical management of essential blepharospasm.

We have reviewed the surgical management of essential blepharospasm over the last 15 years, comparing the results from facial nerve avulsion with those from orbicularis muscle stripping. After facial nerve avulsion 50% of patients remained free of troublesome spasm for 15 months after surgery, but only 25% remained so for more than two years. Following orbicularis oculi myectomy 50% of patients were free of troublesome spasms for 30 months after surgery and 55% of patients had relief from spasm for more than two years. Secondary effects of the two procedures are compared and are found to be fewer after orbicularis myectomy. There were no major complications after either form of surgery. Botulinum toxin is the treatment of first choice for this condition. If this becomes ineffective or inconvenient, surgical treatment is warranted and should not be deferred for fear of severe side effects of treatment, since these are rare. Protractor myectomy gives longer relief from blepharospasm than facial nerve avulsion and has fewer complications. However, it is technically difficult, time consuming, and has greater peroperative morbidity. Facial nerve avulsion may therefore still have a role in selected patients.

Blepharospasm: a review of 264 patients.

The natural history and response to different treatments have been evaluated in 264 patients with blepharospasm. The mean age of onset was 55.8 years and there was a female preponderance of 1.8 to 1. Dystonia elsewhere was found in 78% of patients, usually in the cranial-cervical region, and appeared to follow a somatotopic progression. A family history of blepharospasm or dystonia elsewhere was found in 9.5% of cases, which suggests a genetic predisposition. Ocular lesions preceded the onset of blepharospasm in 12.1% of cases. The response to drugs was inconsistent, although initial improvement was experienced by one fifth of patients treated with anticholinergics. Twenty-nine bilateral facial nerve avulsion operations were performed with benefit in 27 cases; but recurrences appeared in 22, on average one year after surgery. Botulinum toxin injections were performed in 151 patients. Significant improvement was achieved in 118 cases. Mean duration of benefit was 9.2 weeks. Transient ptosis and diplopia were the commonest side effects.