Leprosy affects facial nerves in a scattered distribution from the main trunk to all peripheral branches and neurolysis improves muscle function of the face.
(57/372)
Current literature rejects nerve release in leprous facial neuropathy and states that lesions are restricted to the peripheral zygomatic branches. Since there are approximately 500,000 patients with this disease throughout the world, we wanted to clarify the precise location of facial nerve's affection and the benefit of neurolysis. Our study showed that in patients with leprosy, the facial nerve's main trunk, the peripheral zygomatic branches, and all other branches were affected. Follow-up showed improvement in lagophthalmos and in misreinnervation, with no improvement in the control cohort. Nerve release improves muscle function in leprous facial neuropathy, provided surgery is performed on all affected segments. Intraoperative electroneurodiagnostics is an effective tool for detecting the most proximal site of lesion and ensuring effective surgery. (+info)
Induction of NMDA and GABAA receptor-mediated Ca2+ oscillations with KCC2 mRNA downregulation in injured facial motoneurons.
(58/372)
To clarify the changes that occur in gamma-aminobutyric acid type A (GABA(A)) receptor-mediated effects and contribute to alterations in the network activities after neuronal injury, we studied intracellular Ca(2+) concentration ([Ca(2+)](i)) dynamics in a rat facial-nerve-transection model. In facial motoneurons, an elevation of the resting [Ca(2+)](i), GABA-mediated [Ca(2+)](i) transients, enhancement of the glutamate-evoked [Ca(2+)](i) increases, and spontaneous [Ca(2+)](i) oscillations were induced by axotomy. All these axotomy-induced modifications were abolished by the GABA(A)-receptor antagonist bicuculline and N-methyl-d-aspartate (NMDA)-receptor antagonist d(-)-2-amino-5-phosphonopentanoic acid. A downregulation of K(+)-Cl(-) cotransporter (KCC2) mRNA, an increase in intracellular Cl(-) concentration ([Cl(-)](i)), and transformation of GABAergic hyperpolarization to depolarization were also induced by axotomy. We suggest that in axotomized neurons KCC2 downregulation impairs Cl(-) homeostasis and makes GABA act depolarizing, resulting in endogenous GABA inducing [Ca(2+)](i) oscillations via facilitation of NMDA-receptor activation. Such GABA(A)-receptor-mediated [Ca(2+)](i) oscillations may play a role in neural survival and regeneration. (+info)
Therapeutic vaccine for acute and chronic motor neuron diseases: implications for amyotrophic lateral sclerosis.
(59/372)
Therapeutic vaccination with Copaxone (glatiramer acetate, Cop-1) protects motor neurons against acute and chronic degenerative conditions. In acute degeneration after facial nerve axotomy, the number of surviving motor neurons was almost two times higher in Cop-1-vaccinated mice than in nonvaccinated mice, or in mice injected with PBS emulsified in complete Freund's adjuvant (P < 0.05). In mice that express the mutant human gene Cu/Zn superoxide dismutase G93A (SOD1), and therefore simulate the chronic human motor neuron disease amyotrophic lateral sclerosis, Cop-1 vaccination prolonged life span compared to untreated matched controls, from 211 +/- 7 days (n = 15) to 263 +/- 8 days (n = 14; P < 0.0001). Our studies show that vaccination significantly improved motor activity. In line with the experimentally based concept of protective autoimmunity, these findings suggest that Cop-1 vaccination boosts the local immune response needed to combat destructive self-compounds associated with motor neuron death. Its differential action in CNS autoimmune diseases and neurodegenerative disorders, depending on the regimen used, allows its use as a therapy for either condition. Daily administration of Cop-1 is an approved treatment for multiple sclerosis. The protocol for non-autoimmune neurodegenerative diseases such as amyotrophic lateral sclerosis, remains to be established by future studies. (+info)
Development of synchronized activity of cranial motor neurons in the segmented embryonic mouse hindbrain.
(60/372)
Spontaneous electrical activity synchronized among groups of related neurons is a widespread and important feature of central nervous system development. Among the many places from which spontaneous rhythmic activity has been recorded early in development are the cranial motor nerve roots that exit the hindbrain, the motor neuron pool that, at birth, will control the rhythmic motor patterns of swallow, feeding and the oral components of respiratory behaviour. Understanding the mechanism and significance of this hindbrain activity, however, has been hampered by the difficulty of identifying and recording from individual hindbrain motor neurons in living tissue. We have used retrograde labelling to identify living cranial branchiomeric motor neurons in the hindbrain, and [Ca2+]i imaging of such labelled cells to measure spontaneous activity simultaneously in groups of motor neuron somata. We find that branchiomeric motor neurons of the trigeminal and facial nerves generate spontaneous [Ca2+]i transients throughout the developmental period E9.5 to E11.5. During this two-day period the activity changes from low-frequency, long-duration events that are tetrodotoxin insensitive and poorly coordinated among cells, to high-frequency short-duration events that are tetrodotoxin sensitive and tightly coordinated throughout the motor neuron population. This early synchronization may be crucial for correct neuron-target development. (+info)
Transmembrane sema4E guides branchiomotor axons to their targets in zebrafish.
(61/372)
Class 4 semaphorins are a large class of transmembrane proteins that contain a sema domain and that are expressed in the CNS, but their in vivo neural function is unknown. In zebrafish, the epithelial cells that line the pharyngeal arches express Sema4E. Extension of branchiomotor axons along the mesenchymal cells bounded by these epithelial cells suggests that Sema4E may act as a repulsive guidance molecule to restrict the branchiomotor axons to the mesenchymal cells. To test this hypothesis, Sema4E was misexpressed in hsp70 promoter-regulated transgenic zebrafish in which sema4E was heat-inducible, and Sema4E was knocked down by injection of antisense morpholino oligonucleotides that acted specifically against Sema4E. Ubiquitous induction of Sema4E retarded outgrowth by the facial and gill branchiomotor axons significantly. Furthermore, outgrowth by gill motor axons was specifically inhibited when Sema4E-expressing transgenic cells were transplanted to their pathway in nontransgenic host embryos. Morpholino knockdown of Sema4E caused facial motor axons to defasciculate and follow aberrant pathways. These results show that Sema4E is repulsive for facial and gill motor axons and functions as a barrier for these axons within the pharyngeal arches. (+info)
Congenital bifurcation of the intratemporal facial nerve.
(62/372)
Anomalies of the course of the facial nerve have been reported in association with middle and inner ear malformations. Bifurcation of its intratemporal portion is a rare malformation in which focal splitting of one or more facial nerve segments occurs. We describe the CT appearance of this anomaly and discuss its possible embryology. Facial nerve bifurcation is important to recognize in patients undergoing evaluation for congenital hearing loss and other congenital ear malformations. (+info)
In vivo application of mitochondrial pore inhibitors blocks the induction of apoptosis in axotomized neonatal facial motoneurons.
(63/372)
Axotomy induces apoptosis in motoneurons of neonatal rodents. To identify the key players in motoneuron apoptosis, we assessed the progression of apoptosis at 4 h intervals following facial motoneuron axotomy. The mitochondrial release of cytochrome c, caspase-3 activation and nuclear condensation were first observed in the motoneuron cell bodies 16 h postaxotomy. In vivo application of inhibitors of the mitochondrial permeability transition pore, Bongkrekic acid and cyclosporin A prevented cytochrome c release as well as caspase-3 activation and attenuated motoneuron apoptosis. Similarly, in vivo application of RU360, an inhibitor of the mitochondrial calcium uniporter, also protected axotomized motoneurons from apoptosis. Taken together, our results show that cytochrome c release and subsequent caspase-3 activation are critical events that precipitate the apoptotic death of axotomized neonatal motoneurons in vivo. In addition, these results provide evidence that application of mitochondrial pore inhibitors in vivo can block the induction of apoptosis following motoneuron axotomy. (+info)
Fas/tumor necrosis factor receptor death signaling is required for axotomy-induced death of motoneurons in vivo.
(64/372)
Activation of the Fas death receptor leads to the death of motoneurons in culture. To investigate the role of Fas in programmed cell death and pathological situations, we used several mutant mice deficient for Fas signaling and made a novel transgenic FADD-DN (FAS-associated death domain-dominant-negative) strain. In vitro, motoneurons from all of these mice were found to be resistant to Fas activation and to show a delay in trophic deprivation-induced death. During normal development in vivo, no changes in motoneuron survival were observed. However, the number of surviving motoneurons was twofold higher in animals deficient for Fas signaling after facial nerve transection in neonatal mice. These results reveal a novel role for Fas as a trigger of axotomy-induced death and suggest that the Fas pathway may be activated in pathological degeneration of motoneurons. (+info)