Normal Nerve Fibers Research Articles

Axon-Schwann cell networks are regular components of nodal regions in normal large nerve fibres of cat spinal roots

The paranodal occurrence of axon-Schwann cell networks (ASNs), which are entities assumed to take part in the removal of degenerate axonal material, was examined quantitatively by electron microscopical serial section analysis in normal cat ventral and dorsal spinal roots. In nerve fibres greater than or equal to 10 microns in diameter 88% of the nodal regions in the ventral roots and 97% in the dorsal roots showed ASN complexes, which especially in the ventral roots often consisted of many segregated axoplasmic portions. The corresponding frequencies in fibres less than 10 microns were 28% and 62% in the ventral and the dorsal roots, respectively. ASN complexes were rare in fibres less than 5 microns. The results show that the ASN is a part of the normal paranodal architecture in large myelinated nerve fibres. The ASN occurrence seems to differ with neurone type.

The Retinal Nerve Fiber Layer in Normal Eyes

The retinal nerve fiber layer is different in normal and glaucomatous eyes. The authors used red-free photographs to examine the retinal nerve fiber layer in 234 normal eyes. The retinal nerve fiber layer was most visible in the inferior temporal arcade, followed by the superior temporal arcade, then by the temporal macular area, and finally the nasal area. This distribution was significantly (P < 0.0001) correlated to (1) the configuration of the neuroretinal rim, which was significantly broadest at the inferior disc pole followed by the superior one, (2) the juxtapapillary caliber of the retinal vessels, which were significantly wider in the inferior temporal arcade than in the superior temporal arcade, and (3) the location of the foveola 0.53 ± 0.34 mm inferior to the middle point of the vertical optic disc axis. The retinal nerve fiber layer decreased with age. No correlation occurred with sex or right or left eye. No localized retinal nerve fiber layer defects were seen. These features of the normal retinal nerve fiber layer are important for diagnosis of retinal nerve fiber layer changes secondary to optic nerve damage in the diseased eye.

Decrease of vasoactive intestinal peptide, methionine-enkephalin, substance P and increase of neuropeptide Y immunoreactive nerve fibres in aganglionic colon of Hirschsprung's disease

Ganglionic and aganglionic full-thickness samples, at 4 levels of the colon of 26 infants with Hirschsprung's disease, were studied by immunohistochemistry. In the distal part of the aganglionic bowel, we observe a decrease of substance P and vasoactive intestinal peptide, an absence of methionine-enkephalin and an increase in neuropeptide Y nerve fibres. When detected, substance P and vasointestinal peptide are mainly present in abnormal bundle nerve fibres. In the middle part of the aganglionic bowel, a slight increase in the number of normal nerve fibres containing substance P, methionine-enkephalin and vasoactive intestinal peptide is observed. Some vasoactive intestinal peptide abnormal bundle nerve fibres are detected. They are less numerous than in the distal part. In the proximal ganglionic bowel, the number of vasoactive intestinal peptide, substance P and methionine-enkephalin normal nerve fibres is increased compared to the middle aganglionic segment but is slightly lower than in the normal colon. Again vasoactive intestinal peptide abnormal bundle nerve fibres are present at that level and are also detected in more proximal ganglionic bowel up to the hepatic flexure of the colon. Thus, abnormal distribution of neuropeptides is also found in more proximal ganglionic bowel and not only in the aganglionic segment of bowel usually specific of Hirschsprung's disease.

Ophthalmic changes in hydrocephalus

Fifty children shunted for hydrocephalus aged 5-17 years underwent a later ophthalmological examination. Corrected vision of 0.9 or less was found in 45 out of 93 eyes; in 21 patients this was the vision of both eyes. Corrected vision 0.3 or less was found in 7 eyes; in 3 patients this was the vision of both eyes. Hyperopia greater than or equal to +2.0 D was found in 20%, myopia greater than or equal to -0.5 D in 13% and astigmatism greater than or equal to 1.0 D in 25.5% of 98 eyes. Clear nystagmus was present in 18% of patients. Heterophoria was found in 20% and manifest horizontal strabismus in 33%, but no paretic squint. The optic disc was considered normal in 36 out of 100 eyes on ophthalmoscopy and in 35 out of 78 eyes on colour photography. Retinal nerve fibre layer photographs showed normal nerve fibres in 49 out of 71 eyes. The Friedmann field was in the normal range in 33 out of 53 eyes, and the Goldmann field was normal in 37 out of 44 eyes. Right homonymous hemianopia was discovered in 2 patients. The Harrington-Flocks field was normal in 17 out of 24 eyes, and 1 patient had left homonymous hemianopia. The HRR test showed a red-green disturbance in 22 out of 71 eyes. The Farnsworth panel D-15 desaturated test was entirely normal in only 4 out of 65 eyes, but the errors were only slight in 48 cases.

Fluorescent findings of the facial nerve at decompression operation

We performed decompression operation in cases of Bell's palsy, traumatic facial nerve palsy of the temporal bone and otogenic facial nerve palsy. At the time of decompression operation, a fluorescent flow in the facial nerve trunk was measured by means of the intravenous injection of a fluorescent substance which is used for the eyes fundus examination.The relation between prognosis and fluorescent flow were compared. Experimental studies were performed using the rabbits in orders to obtain basic information.The results were obtained as follows: In Bell's palsy, each 5 cases showed a fluorecence ranged from slight to well but there was no case of complete cure. However, there was a tendency of cure in cases with a good fluorescence. On the other hand, in traumatic and otogenic facial nerve palsy there were cases of complete cure although neither response in the maximal stimulation test nor fluorescence in the nerve.It is thought that there is a difference of pathophysiological condition between Bell's palsy and traumatic or otogenic facial nerve palsy.A fluorescent flow in the extratemporal portion of the facial nerve was seen from the distal side to the proximal side.On the contrary, in the intratemporal portion of the facial nerve it was seen from the proximal side to the distal side. Measurement of the fluorescent flow and neuropathological exmination of the facial nerve were made after the experimental nerve damage such as crush or incision. The milder nerve damage, the better fluorescence of the nerve trunk was seen. The regenerated nerve fibers showed a good fluorescence as well as normal nerve fibers.

The Fiber Arrangement of the Human Recurrent Laryngeal Nerve

The fiber arrangement of the normal left-sided recurrent laryngeal nerve at the level of second to eighth tracheal cartilage was examined mainly by SEM after the removal of connective tissue components of surrounding the nerve fibers. Formalin-fixed specimens were taken by autopsy from eight individuals, then refixed with glutaraldehyde, hydrolyzed with hydrochloric acid (HCl), digested with collagenase, and processed for SEM observation.Extracellular materials such as fibroblasts and collagen fibers were completely digested, and each nerve fiber was exposed and clearly visible under the SEM. The nerve bundles were composed of parallel running and slightly wavy fibers which practically lacked anastomosis. Fibers with Ranvier's nodes were occasionally observed and definitely identified as the myelinated type. However, its accurate ratio in the recurrent nerve was not yet determined in the present study.By means of SEM in combination with the digestion method (Evan et al., 1975), it was quite easy to obtain the precise stereoscopic image of the course and arrangement of the normal human recurrent laryngeal nerve fibers. This method will be useful to detect pathological changes, such as post-paralytic, misdirected innervation, and neurinoma.

Nerve fiber planimetry in acute and chronic nerve lesions and in nerve lesions in continuity.

The level of resection of damaged nerve tissue in acute and chronic nerve lesions was determined on the basis of the vascular structure, the consistency of the nerve during palpation, the amount of interfascicular connective tissue, and the mushroom formation of the fascicles. Intraoperative electrophysiologic recordings were performed on the cut nerve ends to determine the function of the axons. Postoperative planimetric analyses of cross sections made through the resected nerve stumps were performed to measure axonal and endoneural tube diameters and to correlate these results with the clinical criteria used through the operating microscope. Axons in the proximal nerve ends of acute and chronic nerve lesions displayed a similar mean diameter. Endoneural tubes in chronic nerve lesions shrunk significantly as nerve repair was delayed. In several nerve lesions in continuity, axons remained present across the injured site despite absence of electrical conduction. When comparing the results of axonal or endoneural tube diameters of chronic nerve lesions to the results of other studies or acute nerve lesions, we demonstrated that careful examination through the operating microscope provided valid information about the proper management and resection level of chronic nerve lesions. Electrophysiologic evaluation aided the surgical management but was not useful for the resection of the distal damaged nerve segment. The presence of an evoked potential in the proximal nerve ends guaranteed a nearly normal nerve fiber diameter distribution, while the absence of such a potential in the distal nerve ends indicated an abnormal, absent, or disturbed endoneural tube diameter histogram.

Immature and mature neurofilament-immunoreactive trigeminal fibers can innervate the iris as studied by intraocular grafting of iris and trigeminal ganglia

Using immunohistochemistry on stretch-prepared whole mounts of adult rat irides, a dense, well-organized plexus of neurofilament-positive nerves originating in the trigeminal ganglion can be visualized. Such a two-dimensional tissue preparation is well-suited for studies on sensory and autonomie nerve fiber growth. In the present study the growth capacity of such neurofilament-positive nerves has been studied immunohistochemically. In irides homologously transplanted to the anterior eye chamber of adult albino rats, the intrinsic neurofilament-positive network had almost completely disappeared 4 days postoperatively. In whole mounts of iris grafts after 15 days and 4 weeks in oculo a gradually increasing plexus of nerves was observed. After 3.5 months in oculo a dense, regular network of fluorescent fibers had formed in the iris grafts to the same magnitude as in situ. However, whereas large axon bundles constituted a prominent feature of the distribution of neurofilament-positive nerves in situ, only a few and relatively thin axon bundles were seen in the grafts. The growth capacity of the neurofilament-positive trigeminal nerves was also studied by grafting fetal trigeminal ganglia to the anterior eye chamber. As visualized in cryostat sections, trigeminal grafts contained a large number of strongly fluorescent perikarya and a high density of positive fibers after intraocular maturation. Such grafts readily innervated the host iris. In the area immediately adjacent to the grafts, thin, parallel, rather weakly fluorescent fibers radiated out from the ganglia. When mature trigeminal grafts with attached host iris were regrafted to the anterior eye chamber of adult animals for a few days, in order to remove the intrinsic host iris innervation, such irides showed outgrowing fibers, often organized in small axon bundles, at long distances from the ganglion graft. The present report shows that both mature and immature neurofilament-immunoreactive neurons are capable of innervating the iris. Furthermore, this ingrowth can occur both in the presence and absence of normal intrinsic neurofilament-positive nerve fibers.

Development of trochlear motor neurons, superior oblique muscle, and neuromuscular junctions following prevention of cell death by myasthenia gravis immunoglobulin

Paralysis of embryo during the period of naturally occurring motor neuron death produces an increase in the number of surviving neurons while the progressive differentiation and maturation of target muscle is severely retarded. Application of immunoglobulin G from patients with acquired myasthenia gravis to duck embryos during the period of trochlear motor neuron death also prevents this neuron loss but without paralyzing the embryo. The present study was conducted to investigate whether or not the differentiation and maturation of motor neurons, target muscle, and neuromuscular junctions were retarded following prevention of cell loss with myasthenic immunoglobulin. Immunoglobulin concentrates from myasthenics and normal human volunteers were applied daily to the chorioallantoic membrane of duck embryos from day 10 onward. The development of the trochlear neurons and the superior oblique muscle was examined with light and electron microscopy on embryonic days 12, 16 and 20. The motor neurons at the light and electron microscopic level were cytologically indistinguishable between the myasthenic and normal immunoglobulin-treated embryos. Myoblasts fused to form myotubes. which further differentiated into mature myofibers at the same time in both groups. Numerous neuromuscular junctions of normal ultrastructure and nerve fibers with myelin wrappings were observed in both cases. It is concluded that the increased neuron survival following myasthenic immunoglobulin treatment does not accompany retardation in differentiation and maturation of the target muscle which is contrary to the results obtained from studies utilizing neuromuscular blocking agents producing increased cell survival.

Function of myelin in the normal nerve fibre.

Function of myelin in the normal nerve fibre.

Changes in the compact myelin of single internodes during axonal atrophy.

Distal axonal atrophy was produced by proximal constriction of the tibial nerve in the rabbit. Transverse sections were studied by light and electron microscopy at 10 micron intervals along individual internodes of both atrophic and normal tibial nerve fibres. During axonal atrophy there were marked changes in axonal configuration at different levels within the territory of a single Schwann cell. These resulted in changes in the lengths of the axon perimeter and myelin spiral, without causing any alteration in the numbers of myelin lamellae or their spacing. Comparable changes in axon perimeter and myelin spiral length were seen in transverse sections through the paranodal and nuclear regions of normal fibres. These results show that local variations in axonal calibre or shape are associated with appropriate adjustments to the length of the myelin spiral, without a change in the number of lamellae, and thus of sheath thickness.

Basic Study on Tinnitus

In order to elucidate the pathogeneses of tinnitus, the etiology of tinnitus was reviewed in the litrature and the change in the spontaneous activity of the cochlear nerve was examined after the application of sodium chloride crystals to the round window membrane of the guinea pig. The results of this experiment was as follows: In two cases out of three, the spontaneous discharge increased remarkably 10min, after the application of sodium chloride, and the pattern of firing was bursty discharge which normal auditory nerve fibers do not exhibit. On the other hand, the remain showed the hyperactivity temporally and thereafter the discharge was supressed extensively. These abnormal discharges of cochlear nerve fibers was thought to be able to cause tinnitus.

Regenerating mammalian nerve fibres: changes in action potential waveform and firing characteristics following blockage of potassium conductance.

Extracellular application of potassium channel blocking agents is known to increase the amplitude and duration of the compound action potential in non-myelinated and demyelinated axons, but not in mature mammalian myelinated fibres. In the present study we used intra-axonal and whole nerve recording techniques to study the effects of the potassium channel blocking agent 4-aminopyridine (4-AP) on regenerating rat nerve fibres. Our results indicate that early regenerating (premyelinated) axons show considerable broadening of the action potential after 4-AP application and late regenerating (myelinated) axons give rise to burst activity following a single stimulus after 4-AP application. 4-AP did not affect spike waveform or firing properties of normal mature sciatic nerve fibres. These results demonstrate the importance of potassium conductance in stabilizing firing properties of myelinated regenerating axons.

Hirschsprung's Disease in a Family with Multiple Endocrine Neoplasia Type 2

SummaryGastrointestinal symptoms are known to occur in association with multiple endocrine neoplasia (MEN) type 2. Patients with the variant 2b are at special risk and show diffuse intestinal ganglioneuromatosis. Megacolon is frequently an early X‐ray finding and is associated with hyperplastic ganglion cells and nerve plexuses. The unusual association of MEN type 2a with aganglionic megacolon is described in a kindred of 92 individuals. There were 15 cases of medullary thyroid carcinoma (MTC), one case each of pheochromocytoma and hyperparathyroidism, and eight cases of Hirschsprung's disease (five histologically proven). In these eight patients, the neonatal period was characterized by a delay in the passage of meconium. Three infants died from intestinal obstruction within the first 2 weeks of life. The diagnosis was missed in one girl who died despite laparotomy. Pull‐through procedures were successfully performed in three other infants. The last individual suffered from constipation and several bouts of intestinal obstruction before being operated on at the age of 19. He was subsequently found to have MTC and underwent surgery, but recurrence was recently documented. The four living patients were reevaluated. Rectal manometry could not elicit internal sphincter relaxation, thus confirming the diagnosis of Hirschsprung's disease. Biopsies of the remaining colon contained normal ganglion cells and nerve fibers, thereby eliminating the possibility of aganglionosis and ganglioneuromatosis in different parts of the large bowel of the same individual. It is concluded that Hirschsprung's disease might be responsible for bowel obstruction in MEN type 2. In familial cases of aganglionic bowel, the possibility of MEN should be ruled out by family history and appropriate testing.

Internodal myelin volume and axon surface area: A relationship determining myelin thickness?

Internodes from normal, remyelinated and regenerated nerve fibres have been isolated from rat spinal roots and sciatic nerve. The internodes have been examined quantitatively by light and electron microscopy to determine their internodal length, myelin thickness, and the circumference and cross-sectional area of both the axon and fibre. Comparison of these measurements of the axon and myelin sheath has revealed a close relationship between the volume of myelin comprising the internode and the area over which the Schwann cell and axon are in close proximity, i.e. the surface area of the axolemma beneath the internodal myelin sheath. The same relationship described not only the internodes on normal nerve fibres, where internodal length is proportional to axon diameter, but also the short and thinly myelinated internodes formed in the adult animal on remyelinated and on regenerated axons. Examination of data presented by Berthold (1978) revealed that a closely similar relationship is also present in feline nerve fibres. In view of the constancy of the relationship between such different types of internode it is suggested that the regulation of myelin volume, and thereby of myelin thickness, may be mediated via the area of the axolemma or of the Schwann cell membrane beneath the myelin sheath.

Morphological Observations of Peripheral Nerves by the Scanning Electron Microscope

In order to observe a normal peripheral nerve and a changed peripheral nerve by means of a scanning electron microscope, the present study was carried out. In the changed nerve fibers, they were enveloped by many processes of hypertrophied Schwann cells, and the processes of the Schwann cells seemed to make a pseudosyntitium-like structure with each other. From this finding, it was speculated that these Schwann cells seemed to follow the reverse process in the development of normal peripheral nerve fibers.

Acetylcholinesterase containing nerve fibers in guinea pig ovary.

The distribution of acetylcholine esterase (AChE) in the ovary of normal as well as of sympathectomized guinea pigs was studied. In normal animals AChE-positive nerve fibres were found organized in a perivascular plexus. Some nerve fibres reach the corpus luteum and the follicular wall. Chemical sympathectomy performed with he neurotoxin 6-hydroxydopamine caused an almost complete disappearance of AChE positive nerve fibres suggesting that most of the AChE activity of ovarian nerves is localized in adrenergic nerve fibres. Enzyme activity was also present in smooth muscle cells of the vascular tree.

Degenerating taste buds in sialectomized rats.

In the present report changes are described in degenerating taste buds (TB) from rats deprived of the main salivary glands (parotid, sublingual and submaxillary glands). These changes include macrophages located inside the degenerating TB cell, lipid droplets and a heterogeneous population of digestive vacuoles. In addition, a large number of bacteria was found to permeate the apical taste pore. It is of interest that normal nerve fibers were seen synapsing with the degenerating TB cells. The sialectomy-induced degeneration of TB would not be, therefore, a consequence of neural deprivation.

Normal nerve fibers in the barrel region of developing and adult mouse cortex.

The pattern of normal nerve fibers associated with barrel-shaped structures in the somatosensory cortex of both young and adult mice, has been studied using a reduced silver method. In adult animals, the "barrel" sides and septa can be seen to contain densely packed bundles of nerve fibers running vertically between layers III and V. In parasagittal sections, these fibers appear as very dark bands between adjacent barrels, while in tangenital sections the fibers, cut in cross-section, appear as rings of dark spots concentrated around the barrel edges. In contrast to this, barrels in immature animals have dark, evenly stained centers and pale, cell dense sides. This immature pattern can first be distinguished in 2-day-old animals and persists until 18 to 19 days. Between 18 and 24 days a change from the immature to the adult pattern occurs with the appearance of darkly stained, fine fibers within layer IV, particularly within the barrel sides. It is suggested that the immature pattern is due, primarily, to the staining of thalamic afferents while the adult pattern appears with the development of intracortical and association fibers. Electron microscopy, on tissue previously treated by the silver method, shows that the silver deposits are mainly attached to longitudinal elements of the axoplasm and not associated with myelin. This may explain the success of this method in showing fibers in young, unmyelinated brains.

Specific staining of the axon membrane at nodes of Ranvier with ferric ion and ferrocyanide

Ferric ion and ferrocyanide were used as stains for light and electron microscopy of peripheral nerves. In rat sciatic nerves, it was found that ferric ion preferentially binds to the cytoplasmic surface of the axon membrane at nodes of Ranvier but not at internodal regions. In myelinated axons in the electric organ of the gymnotid fish, Sternarchus albifrons, the small excitable nodes are similarly stained, but the larger inexcitable nodes are not stained by ferric ion. Staining of the inner surface of the nodal membrane appears to be related to a structural specialization of this membrane, rather than accessibility to stain. Our data thus show a chemical differentiation of the inner surface of the axon membrane between nodes and internodes in normal peripheral nerve fibers and between the inner surface of the axon membrane at active nodes, inactive nodes, and the internodes in the Sternarchus electrocyte axons.