Localized nonlinear waves in a myelinated nerve fiber with self-excitable membrane

We systematically study the evolution of modulated nerve impulses in a myelinated nerve fiber, where both the ionic current and membrane capacitance provide the necessary nonlinear feedbacks. This is achieved by using a perturbation technique, in which the Liénard form of the modified discrete Fitzhugh–Nagumo equation is reduced to the complex Ginzburg–Landau amplitude equation. Three distinct values of the capacitive feedback parameter are considered. At the critical value of the capacitive feedback parameter, it is shown that the dynamics of the system is governed by the dissipative nonlinear Schr?dinger equation. Linear stability analysis of the system depicts the instability of plane waves,which is manifested as burst of modulated nerve impulses that fulfills the Benjamin–Feir criteria. Variations of the capacitive feedback parameter generally influences the plane wave stability and hence the type of wave profile identified in the neural network. Results of numerical simulations mainly confirm the propagation, collision, and annihilation of nerve impulses in the myelinated axon.

Nerve conduction models in myelinated and unmyelinated nerves based on three-dimensional electrostatic interaction

Until now, nerve conduction has been described on the basis of equivalent circuit model and cable theory, both of which supposed closed electric circuits spreading inside and outside the axoplasm. With these conventional models, we can simulate the propagating pattern of action potential along the axonal membrane based on Ohm＇s law and Kirchhoff＇s law. However, we could not fully explain the different conductive patterns in unmyelinated and myelinated nerves with these theories. Also, whether we can really suppose closed electrical circuits in the actual site of the nerves or not has not been fully discussed yet. In this report, a recently introduced new theoretical model of nerve conduction based on electrostatic molecular interactions within the axoplasm will be reviewed. With this new approach, we can explain the different conductive patterns in unmyelinated and myelinated nerves. This new mathematical conductive model based on electrostatic compressional wave in the intracellular fluid may also be able to explain the signal integration in the neuronal cell body and the back-propagation mechanism from the axons to the dendrites. With this new mathematical nerve conduction model based on electrostatic molecular interactions within the intracellular fluid, we may be able to achieve an integrated explanation for the physiological phenomena taking place in the nervous system.

Changes in Myelinated Nerve Fibers and Skeletal Muscle of Rats Exposed to High Doses of Permethrin

Neurological signs and segmcntal demyelination in a cervical nerve were observed in rats treated orally with permethrin (300 mg/kg/day) for 5 days. Inflammatory and degenerative signals were recorded in the diaphragm muscle. These effects were more intense with the trade grade than with the technical grade product. The possible influence of the percentage of cisitrans isomers on the intensity of the observed effects is discussed. 5 imi Academic Press.Inc.

Microperimetry and spectral domain optical coherence tomography in myelinated retinal nerve fibers

Dear Sir,I write to present the correlation between microperimetric （MP） values and the density of myelinated retinal nerve fibers （MNFs） in optical coherence tomography （OCT） imaging.

The mechanism of astragaloside Ⅳ promoting sciatic nerve regeneration

3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosyl-cycloastragenol （astragaloside IV）, the main active component of the traditional Chinese medicine astragalus membranaceus, has been shown to be neuroprotective. This study investigated whether astragaloside IV could promote the repair of injured sciatic nerve. Denervated sciatic nerve of mice was subjected to anastomosis. The mice were intraperitoneally injected with 10, 5, 2.5 mg/kg astragaloside IV per day for 8 consecutive days Western blot assay and real-time PCR results demonstrated that growth-associated protein-43 ex- pression was upregulated in mouse spinal cord segments L4-6 after intervention with 10, 5, 2.5 mg/kg astragaloside IV per day in a dose-dependent manner. Luxol fast blue staining and elec- trophysiological detection suggested that astragaloside IV elevated the number and diameter of myelinated nerve fibers, and simultaneously increased motor nerve conduction velocity and action potential amplitude in the sciatic nerve of mice. These results indicated that astragaloside IV con- tributed to sciatic nerve regeneration and functional recovery in mice. The mechanism underlying this effect may be associated with the upregulation of growth-associated protein-43 expression.

Tacrolimus reduces scar formation and promotes sciatic nerve regeneration

A sciatic nerve transection and repair model was established in Sprague-Dawley rats by transecting the tendon of obturator internus muscle in the greater sciatic foramen and suturing with nylon sutures. The models were treated with tacrolimus gavage （4 mg/kg per day） for 0, 2, 4 and 6 weeks. Specimens were harvested at 6 weeks of intragastric administration. Masson staining revealed that the collagen fiber content and scar area in the nerve anastomosis of the sciatic nerve injury rats were significantly reduced after tacrolimus administration. Hematoxylin-eosin staining showed that tacrolimus significantly increased myelinated nerve fiber density, average axon diameter and myelin sheath thickness. Intragastric administration of tacrolimus also led to a significant increase in the recovery rate of gastrocnemius muscle wet weight and the sciatic functional index after sciatic nerve injury. The above indices were most significantly improved at 6 weeks after of tacrolimus gavage. The myelinated nerve fiber density in the nerve anastomosis and the sciatic nerve functions had a significant negative correlation with the scar area, as detected by Spearman＇s rank correlation analysis. These findings indicate that tacrolimus can promote peripheral nerve regeneration and accelerate the recovery of neurological function through the reduction of scar formation.

Aquaporin-3 Deletion Reduces Glycerol and ATP Content in Mouse Sciatic Nerve

We reported the expression and function of aquaglyceroporin AQP3 in mouse peripheral nervous system.AQP3 mRNA was identified in freshly isolated mouse sciatic nerve by RT-PCR.Immunofluorescence using AQP3 antibody localized the protein expression in the myelin sheathe of sciatic nerve fibers.Although primary morpholo-gical evaluation of sciatic nerves from AQP3-knockout and wildtype mice revealed no significant difference,biochemical analysis demonstrated remarkably decreased glycerol and ATP contents in freshly isolated AQP3-knockout sciatic nerve.The study indicates an important role of facilitated glycerol transport mechanism in peripheral nerve energy metabolism.

Ursolic acid induces neural regeneration after sciatic nerve injury

In this study, we aimed to explore the role of ursolic acid in the neural regeneration of the injured sciatic nerve. BALB/c mice were used to establish models of sciatic nerve injury through unilateral sciatic nerve complete transection and microscopic anastomosis at 0.5 cm below the ischial tuber-osity. The successful y generated model mice were treated with 10, 5, or 2.5 mg/kg ursolic acid via intraperitoneal injection. Enzyme-linked immunosorbent assay results showed that serum S100 protein expression level gradual y increased at 1-4 weeks after sciatic nerve injury, and significantly decreased at 8 weeks. As such, ursolic acid has the capacity to significantly increase S100 protein expression levels. Real-time quantitative PCR showed that S100 mRNA expression in the L 4-6 segments on the injury side was increased after ursolic acid treatment. In addition, the muscular mass index in the soleus muscle was also increased in mice treated with ursolic acid. Toluidine blue staining revealed that the quantity and average diameter of myelinated nerve fibers in the injured sciatic nerve were significantly increased after treatment with ursolic acid. 10 and 5 mg/kg of ursolic acid produced stronger effects than 2.5 mg/kg of ursolic acid. Our findings indicate that ursolic acid can dose-dependently increase S100 expression and promote neural regeneration in BALB/c mice fol owing sciatic nerve injury.

Sensory innervation around immediately vs. delayed loaded implants: a pilot study

Although neurophysiological and psychophysical proof of osseoperception is accumulating, histomorphometric evidence for the neural mechanisms of functional compensation following immediate and delayed implant loading is still lacking. For this randomized split-mouth study, six mongrel dogs randomly received one of four treatment protocols at 36 implant-recipient sites over 16 weeks （third maxillary incisor, third and fourth mandibular premolar）： immediate implant placement and immediate loading （liP＋ IL）; delayed implant placement and delayed loading （DIP＋DL）; delayed implant placement and immediate loading （DIP＋IL）; and natural extraction socket healing （control）. Histomorphometry was performed in the peri-implant bone and soft tissues within 300 pm around the implants. Immunocytochemistry and transmission electron microscopy were used to confirm the presence of neural structures and to reveal their ultrastructural characteristics, respectively. Myelinated nerve fibres densely populated the peri-implant crestal gingival and apical regions, although they were also identified in the woven bone and in the osteons near the implant threads. Compared with the control group in the mandible, the group that received IIP＋IL showed a higher innervation （in N.mm^-2, 5.94±1.12 vs. 3.15±0.63, P〈0.001） and smaller fibre diameter （in pm, 1.37±0.05 vs. 1.64±0.13, P=0.016）, smaller axon diameter （in pm, 0.89±0.05 vs. 1.24±0,10, P=0.009） and g-ratio （0.64±0.04 vs. 0.76±0.05, P〈0.001） in the middle region around the implants. Compared with DIP＋IL in the mandible, IIP＋IL had a higher nerve density （in N.mm^-2, 13.23±2.54 vs. 9.64±1.86, P=0.027）, greater fibre diameter （in pm, 1.32±0.02 vs. 1.20±0.04, P=0.021）, greater axon diameter （in μm, 0.92±0.01 vs. 0.89±0.03, P=-0.035） and lower g-ratio （0.69±0.01 vs. 0.74±0.01, P=-0.033） in the apical region around the implants. It may be assumed that the treatment protocol with liP＋ IL is the preferred method to allow optimized peri-implant re-innervation, but further functional measurements are still required.

Salvianolic acid B protects the myelin sheath around injured spinal cord axons

Salvianolic acid B,an active pharmaceutical compound present in Salvia miltiorrhiza,exerts a neuroprotective effect in animal models of brain and spinal cord injury.Salvianolic acid B can promote recovery of neurological function;however,its protective effect on the myelin sheath after spinal cord injury remains poorly understood.Thus,in this study,in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation,and the most effective dose was 20 μg/m L.For in vivo investigation,rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks.The amount of myelin sheath and the number of regenerating axons increased,neurological function recovered,and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats.These results indicate that salvianolic acid B can protect axons and the myelin sheath,and can promote the recovery of neurological function.Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.

The occurrence of diffuse axonal injury in the brain:associated with the accumulation and clearance of myelin debris

The accumulation of myelin debris may be a major contributor to the inlfammatory response after diffuse axonal injury. In this study, we examined the accumulation and clearance of myelin debris in a rat model of diffuse axonal injury. Oil Red O staining was performed on sections from the cerebral cortex, hippocampus and brain stem to identify the myelin debris. Seven days after diffuse axonal injury, many Oil Red O-stained particles were observed in the cerebral cortex, hippocampus and brain stem. In the cerebral cortex and hippocampus, the amount of myelin debris peaked at 14 days after injury, and decreased signiifcantly at 28 days. In the brain stem, the amount of myelin debris peaked at 7 days after injury, and decreased signiifcantly at 14 and 28 days. In the cortex and hippocampus, some myelin debris could still be observed at 28 days after diffuse axonal injury. Our ifndings suggest that myelin debris may persist in the rat central ner-vous system after diffuse axonal injury, which would hinder recovery.

Distribution of paired immunoglobulin-like receptor B in the nervous system related to regeneration difficulties after unilateral lumbar spinal cord injury

Paired immunoglobulin-like receptor B（Pir B） is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regeneration. The regulatory effect of Pir B on injured nerves has received a lot of attention. To better understand nerve regeneration inability after spinal cord injury, this study aimed to investigate the distribution of Pir B（via immunofluorescence） in the central nervous system and peripheral nervous system 10 days after injury. Immunoreactivity for Pir B increased in the dorsal root ganglia, sciatic nerves, and spinal cord segments. In the dorsal root ganglia and sciatic nerves, Pir B was mainly distributed along neuronal and axonal membranes. Pir B was found to exhibit a diffuse, intricate distribution in the dorsal and ventral regions. Immunoreactivity for Pir B was enhanced in some cortical neurons located in the bilateral precentral gyri. Overall, the findings suggest a pattern of Pir B immunoreactivity in the nervous system after unilateral spinal transection injury, and also indicate that Pir B may suppress repair after injury.

Axon regeneration impediment: the role of paired immunoglobulin-like receptor B

Regenerative capacity is weak after central nervous system injury because of the absence of an enhancing microenvironment and presence of an inhibitory microenvironment for neuronal and axonal repair. In addition to the Nogo receptor（Ng R）, the paired immunoglobulin-like receptor B（Pir B） is a recently discovered coreceptor of Nogo, myelin-associated glycoprotein, and myelin oligodendrocyte glycoprotein. Concurrent blocking of Ng R and Pir B almost completely eliminates the inhibitory effect of myelin-associated inhibitory molecules on axonal regeneration. Pir B participates in a key pathological process of the nervous system, specifically axonal regeneration inhibition. Pir B is an inhibitory receptor similar to Ng R, but their effects are not identical. This study summarizes the structure, distribution, relationship with common nervous system diseases, and known mechanisms of Pir B, and concludes that Pir B is also distributed in cells of the immune and hematopoietic systems. Further investigations are needed to determine if immunomodulation and blood cell migration involve inhibition of axonal regeneration.