Density Of Myelinated Fibers Research Articles

Morphometric alteration of rat myelinated fibers with aging.

The number, size, density and pathologic alterations of myelinated fibers (MF) of ventral and dorsal roots and of peroneal and sural nerves in groups of female Fischer 344 rats at 10, 20, and 30 months of age were evaluated to characterize nerve changes with old age. Except for minimal changes in the peroneal nerve, no statistically significant alteration in number of MF/nerve or in the fascicular area was associated with aging. The unaltered number was misleading since striking changes in MF size distribution, pathologic alterations of fibers and the presence of regeneration clusters suggested age-related degenerative and regenerative events. These changes were most dramatic in the ventral root, where myelin infolding, myelin separation from axon and ballooning, macrophagia and hyperplasia of Schwann cell nuclei were pronounced. Concomitant with these alterations, axonal atrophy (a reduction in caliber of axons relative to myelin spiral length or number of myelin lamellae) was demonstrated in MF of the ventral root in old age.

A pathological study of a peripheral nerve in a case of neonatal adrenoleukodystrophy

The pathological findings for a sural nerve biopsy specimen in a case of neonatal adrenoleukodystrophy are described. The density and total number of myelinated fibers in the patient showed no significant changes compared with controls. On electric microscopy, however, thickness of the myelin was smaller in the patient than in controls. Some linear or trilamellar inclusion bodies were found in Schwann cells and fibroblasts, similar to those found in X-linked adrenoleukodystrophy. Büngner's bands were also seen on electron microscopy, and myelin ovoids and balls were seen in teased fibers. These results show that a sural nerve biopsy is useful for the diagnosis of neonatal adrenoleukodystrophy. We suspect that axonal or neuronal degeneration occurs with changes in myelin in neonatal adrenoleukodystrophy.

Usefulness of WBN/Kob Rats Characterized by Exo-endocrine Pancreatic Impairment

Spontaneously developed diabetes mellitus was observed in aged males of an inbred strain of Wistar rats, WBN/Kob. Pathohistologically, at 3 months of age, inflammatory cell infiltration, hemorrhage, deposition of hemosiderin and fibrinous exudation around the pancreatic ducts or blood vessels were observed. A gradual increase in fibrous tissue was observed with advancing age. The enlarged interlobular lymphnodes were also observed. At 12 to 24 months of age, the pancreas became atrophic and replaced by the fibrous tissue and adipose tissue. At 24 months of age, deposition of hemosiderin, suggesting the past hemorrhage was also observed in extensive areas. Inflammatory cell infiltration, deposition of hemosiderin and extremely enlarged interlob ular lymphnodes in pancreas suggest the presence of persistent inflammation together with tissue injury. As the restoration of tissue injury, fibrous tissue might abundantly proliferate resulting in pancreatic fibrosis. As for endocrine, islets composed of few endocrine cells were detected and immunohistochemical study showed decreased numbers of not only B cells but also A cells. The pathophysiology of this diabetes mellitus was quite different from that of type I or II diabetes mellitus in man and animals. The WBN/Kob rat is a new strain of spontaneously developed diabetic rats with exocrine pancreatic insufficiency and also available for the spon taneously occurring chronic pancreatitis models. Moreover in this strain, insulin administration is usually not necessary for survival after the onset of diabetes and this strain is adequate for a long-term observation. As for the ocular lesions, around 1 5 months of age, opacity of lens began to appear. Opacity was first observed in the periphery of the lens, then increased rapidly in severity, extending concentrically and centripetally, until total cataracta was developed. The incidence of cataracta in male rats was gradually increased and reached almost 100% at 24 months of age. As for renal lesions, in male diabetic rats, 24 hour urinary total protein excretion began to increase at about 24 months of age and reached to 50-300 mg/24 hrs at 13 to 28 months of age, which was significantly increased compared with those in the age matched male Wistar rats. Electrophoretic analysis revealed urinary protein was almost albumin. In light microscopic examinations, glomeruli with segmental or global increase of mesangeal areas were noted at 17 months of age, developing a marked glomerulosclerosis. In electron microscopic examinations, the glomerular basement membrane in diabetic male rats aged 11 months was already thickened in comparison with that in the age matched male Wistar rats. As for neural lesions, a reduction of motor nerve conduction velocity was demonstrated in diabetic male rats. Morphometrically, diabetic rats has a remarkable decrease in density and diameter of myelinated fibers in comparison with those in control Wistar rats. From the above data, the WBN/Kob rat is also available for an animal model of human diabetic complications.

Comparison between electrophysiologic and morphologic changes in lead induced peripheral neuropathy in rats

Compound nerve action potential (CNAP) of the mixed peripheral nerve is composed of A alpha beta, A delta, and C potentials. All components of CNAPs in the sciatic nerve were recorded by stimulating the tibial nerve of both control and lead-poisoned rats. Marked decrease of nerve conduction velocity and prolonged duration were found in A alpha beta and A delta fibers especially in large myelinated A alpha beta fibers. The amplitude decreased in A alpha beta potential, but the area did not change. In C potential produced by activation of unmyelinated fibers, nerve conduction velocity slightly decreased, but the amplitude and area did not significantly change. Pathologic correlates revealed prominent segmental demyelination with significant decrease of large myelinated fiber densities. Minimal axonal degeneration of unmyelinated fibers was present. We can conclude that electrophysiologic changes in the lead-poisoned rats correlate with pathologic changes in them.

Spinal roots of rats poisoned with methylmercury: Physiology and pathology

The evoked potentials in the ventral and dorsal roots were recorded independently by stimulating the sciatic nerve of both control and methylmercury-poisoned rats. Poisoned rats showed markedly decreased amplitudes but normal latencies of the potentials evoked in the dorsal roots. Potentials evoked in the ventral roots had normal latencies and amplitudes. Pathological correlates indicated acute axonal degeneration of the dorsal roots, with a significant decrease of the large and small myelinated fiber densities. The ventral roots were histologically unremarkable. Our pathological confirmation of the electrophysiologic changes in the methylmercury-poisoned rats enables us to substantially assess the pathophysiological aspects of acute lesions in the spinal roots.

A morphometric study of the carotid sinus nerve in patients with diabetes mellitus and chronic alcoholism

Morphometric studies were performed on the myelinated fibres of the carotid sinus nerve obtained at autopsy from 13 control subjects, 7 patients with diabetes mellitus and 11 with chronic alcoholism. The myelinated fibre-diameter distribution in control nerves was bimodal with peaks at 3–4 μm and at 8–10 μm. The mean myelinated fibre density was 14.8 × 10 3/mm 2 (SD 2.3 × 10 3/mm 2) in control nerves and was significantly reduced in the nerves of diabetics (mean, 11.7 × 10 3/mm 2; SD, 2.2 × 10 3/mm 2), and chronic alcoholics (mean, 12.7 × 10 3/mm 2; SD, 2.1 × 10 3/mm 2), although in 8 of 11 nerves from alcoholics, the density was within the control range. These findings demonstrate that autonomic afferent fibres are damaged in diabetes and chronic alcoholism, and provide a pathological basis for the disturbances of heart rate and blood pressure control in these conditions.

Peripheral neuropathy in myotonic dystrophy: a nerve biopsy study.

Sural nerve biopsies from 13 unselected myotonic dystrophy patients and 6 normal controls were studied morphometrically. The myelinated fiber density was reduced in 11 of the 13 myotonic dystrophy patients, with preferential loss of large myelinated fibers. Unmyelinated fiber densities and diameters were normal. Teased fiber studies commonly revealed focal areas of remyelination and abnormal wrinkling of the myelin sheath. Measurement of internodal length disclosed features of both axonal regeneration and focal demyelination-remyelination. These findings are consistent with a chronic axonopathy of moderate severity, possibly due to axonal atrophy.

Effect of ACTH 4–10 on nerve fiber regeneration after sciatic nerve crush in rabbits: An electrophysiological and morphological study

Crush of sciatic nerve in rabbits supported by morphologic and electrophysiologic data was used to evaluate the effects of ACTH 4–10 on nerve fiber regeneration. Treated animals showed a statistically significant higher regeneration rate than did control rabbits. Fiber density and mean diameters of myelinated nerve fibers were measured in semithin nerve sections at 1 and 3 cm distal from the crushed point at three different time points. Nerve fiber density results were higher in ACTH 4–10 − than in vehicletreated rabbits. This difference showed an unequivocal trend and attained a statistically significant level in the sections 3 cm distal from the crush. ACTH 4–10 seemed therefore to have a beneficial effect on nerve fiber regeneration.

Axons grow in the aging rat but fast transport and acetylcholinesterase content remain unchanged

Caliber and microtubular density of myelinated fibers, acetylcholinesterase (AChE) content and its accumulation at a ligature were studied in the phrenic nerve of mature (3–4 months) and aging (2-year-old) rats. The number of axons remained constant. The cross-sectional area of the nerve was 67% greater in the older group; the axoplasm, though, constituted about 20% of the nerve tissue irrespective of age. The mean cross-sectional area of myelinated axons was twice as big in aging compared to mature rats. All axons grew in the same proportion irrespective of their original caliber. The microtubular density of 3-μm axons was about 22 microtubules/μm 2 in mature and aging rats. The AChE activity of aging rats was half as much as that of mature rats if it was expressed per wet weight of nerve tissue but did not change if it was expressed per nerve fiber. Twenty-four hours after ligation of the nerve, total AChE activity rose in mature and aging rats by ca. 168%; the molecular forms - asymmetric and globular — accumulated in the same proportion in both age groups. We conclude that myelinated axons grow in the adult stage of life but the structure of axoplasm, content of AChE per axon, and rate of fast transport remain lifelong features of nerve fibers.

The Leprous Neuritis of The Lower Limbs

Peripheral nerves of lower limbs from autopsied cases with so-called arrested leprosy (19 lepromatous leprosy and 16 tuberculoid one) were examined histopathologically. The results were as follows ;1. In lepromatous type, pattern and degree of damage of nerve trunks, reduction of myelinated fibers and frequency of M. leprae were almost same in all cases. The sural and peroneal nerves were more damaged than posterior tibial and sciatic nerves. And in same nerve trunk, more distally more heavily damaged.2. Active demyelinations with M. leprae between myelin lamellae, without foreign cells around Schwann cells were frequently observed in proximal sites in lepromatouscases. Teased fibers showed that it proceeded centripetally and was not type of segmental demyelination. Many reserved naked large axons were also found without remyelination.3. Though pattern and distribution of nerve damages of tuberculoid type were basically same as those of lepromatous type, their degrees were different between each cases. M, leprae/foamy cells were not observed.4. The densities of myelinated fibers were remarkably different between nerve fasci-cles and even in same fascicles. They were thought to be due to results of leprous reactions and demyelinations. In addition, finding resembled to Renaut's body was discussed.The possible mechanism of leprous neuritis was briefly discussed. In lepromatous leprosy, M. leprae mainly enter nerve trunks through distally running dermal nerves and primarily demyelinate sensory fibers centripetally during patients' lives. Leprous reactions secondarily involve motor nerves together. During repetitive reactions at different levels, distal nerve trunks are more damaged under anatomical rules of peripheral nerves. The proximal nerve damages in tuberculoid leprosy, without M. leprae are thought to be due to active old day's leprous reactions, of which target M. leprae, had invaded there not via blood stream, but through dermal nerves originating directly from proximal nerves.As far as to nerves in lower legs, most possible portal of entry seems to be areas of course of sural and peroneal nerves. And transmission of the soils to seems to be more reasonable than that of to man . The author recommend that trial of taking shoes in endemic areas, might be worth for preventing leprosy.

Peripheral nerve findings in Rett syndrome.

Sural nerve and peroneus brevis muscle biopsies were studied in 12 patients with Rett syndrome, ten with the typical form of the disorder according to 1985 criteria, and two with atypical features. Ages ranged from 23 months to 25 years. All stages of the disease were represented. There was evidence of a mild axonal neuropathy in seven of 12 patients. Degenerative and occasional regenerative changes were seen in five sural nerve biopsies, including one from the youngest patient in the series, who was normally nourished and fully ambulatory. Occasional nonspecific ultrastructural abnormalities were present, including accumulation of pi granules in Schwann cells and Hirano bodies within axons. However, morphometric analysis of the four nerves in which these alterations were most prominent showed a normal density and size distribution of myelinated fibers. Enzyme histochemistry of the peroneus brevis biopsies demonstrated abnormal predominance of type II muscle fibers in three of the 12 biopsies and atrophy of type I fibers in one patient.

Quantitative histologic study of sural nerves in xeroderma pigmentosum

The sural nerves of 2 siblings, 7 and 6 years of age with Group A xeroderma pigmentosum, were biopsied. The densities of myelinated fibers, 5,808/mm 2 and 5,163/mm 2, respectively, were strikingly decreased in comparison to control data. Both large and small myelinated fibers were reduced. Electron microscopy demonstrated many collagen fibers in the endoneurium and some collagen pockets. The loss of myelinated fibers was less severe than in previously reported patients. This discrepancy may be due to age differences at biopsy; our patients were biopsied at the ages of 7 and 6 years, while those patients reported previously were 10 years of age or older. The incidence of neurologic manifestations in xeroderma pigmentosum may increase after 6 years of age.

Pathological changes in the vagus nerve in diabetes and chronic alcoholism.

The pathological changes in the vagus nerve removed at necropsy have been studied in patients with chronic alcoholism and diabetes. Morphometric studies on myelinated fibres were performed on the nerve at mid-cervical, lung hilum and diaphragmatic levels. In two insulin-dependent diabetics the density of myelinated fibres was below the lower limit of the control range at all levels. In all the diabetic and chronic alcoholic subjects there was significant reduction in the density of myelinated fibres at the most distal level in the nerve. The degenerative changes in the nerve are consistent with the findings of abnormal vagal function in diabetics and chronic alcoholics.

Morphometric studies of sural nerve in childhood.

Sural nerve myelinated fiber density and myelinated fiber diameter distribution have been examined in 27 control subjects, ranging in age from 1 day to 59 years. Total transverse fascicular area was measured in 10 of the subjects. There is an exponential decline in myelinated fiber density from birth to adult life. The predicted normal density (D) at any age may be derived from the formula D = (1 X 10(3]/(0.0699 + 0.00725 square root t). The distribution of myelinated fiber diameters is unimodal in the first 4 months of life, and there is a definite bimodal distribution by 2 years of age. Total transverse fascicular area of sural nerve increases progressively from values of about 0.25 mm2 in the first week to about 0.82 mm2 at 9 years. Control values for sural nerve morphometry in childhood are essential for accurate interpretation of biopsies in patients with peripheral neuropathy.

Hypotrophic and dying-back nerve fibers in Friedreich's ataxia.

Eight patients with Friedreich's ataxia showed profound reduction in the density of large myelinated fibers in sural nerve biopsies. The density of small myelinated fibers was normal, but the axonal size and myelin thickness were reduced. Demyelination, presumably secondary to axonal dysfunction, was observed in 3% of the isolated fibers. There was axonal degeneration, including dying-back axons isolated in three specimens, in 2.6% of the isolated fibers. The low incidence of degenerating fibers did not account for loss of myelinated fibers in children. There is probably a defect in maturation of fibers, followed by a dying-back process.

Peripheral neuropathy associated with mitochondrial myopathy

Twenty patients with mitochondrial myopathy were investigated for the presence of peripheral neuropathy. There were clinical features of a mild sensorimotor neuropathy in 5 patients (25%) and nerve conduction studies were abnormal in 10 patients (50%). Electrophysiological studies of the whole group showed significant impairment of motor and sensory conduction, compared with controls. Sural nerve biopsy and morphometric studies were performed on 4 patients with clinical neuropathy. There was a reduction in density of myelinated fibers and electron microscope features of axonal degeneration affecting myelinated and unmyelinated fibers. Abnormal mitochondria containing paracrystalline inclusions were seen in the Schwann cell cytoplasm of two nerves.

Pathogenesis of diabetic neuropathy.

Samples of lumbosacral trunk, posterior tibial nerve, and sural nerve obtained at autopsy from diabetic and nondiabetic patients without mononeuropathy multiplex were evaluated using 1-mu-thick epoxy sections and teased nerve fiber preparations. Focal fascicular lesions characterized by reduced density of myelinated axons within fascicles were found predominantly in the specimens from diabetics, mainly in the posterior tibial nerve and lumbosacral trunk. In severe examples, the perineurium and even surrounding epineurium were damaged, stamping the lesions as ischemic. In addition, identical lesions were found in biopsies of nerves of nondiabetics with vasculitis. Density of myelinated fibers at the three sites demonstrated a proximal-distal graded loss that was significantly greater in the diabetic samples. The loss from the lumbosacral trunk to the posterior tibial nerve was correlated with the density of focal lesions in the lumbosacral trunk in the diabetic (p = 0.025), indicating that distal fiber loss was partly due to the focal lesions. Teased nerve fiber abnormalities were common only in sural nerves of diabetics, suggesting that they are secondary. We conclude that beyond the possible metabolic abnormalities involved in the genesis of diabetic polyneuropathy, focal fascicular lesions, likely due to diabetic microangiopathy, are also important in the development of diabetic neuropathy.

Morphological and functional effects of triiodothyronine on regenerating peripheral nerve

The functional and morphologic consequences of treatment of peripheral nerve lesions with exogenous 3,3′,5-triiodo- l-thyronine (T 3) are unclear. In this study adult wistar rats with sciatic nerve crush lesions were treated with 20 μg/kg/day of T 3. The treated animals gained weight though more slowly than vehicle-treated rats. Ten control and 10 experimental animals assessed 4 days postoperatively for sensory axon regeneration by the “pinch test” showed no significant difference in distance regenerated. Motor function recovery was monitored for 21 days after nerve crush lesions by the vestibular placing response and also showed no significant difference. Light microscopy of transverse epoxy sections of the sciatic nerve 5 mm distal to the lesion showed no significant difference in whole nerve area or myelinated fiber density but quantitative electron microscopy revealed a significant increase in axolemma, myelin spiral length, whole nerve fiber area, and nerve fiber perimeter in T 3-treated rats. Statistically non-significant increases in axonal area and myelin periodicity were also noted. These results are interpreted as indicating that although T 3 treatment is not functionally beneficial in the regeneration of adult mammalian peripheral nerve it nonetheless has subtle morphologic effects that indicate a stimulating effect on membrane synthesis.

Effect of protein calorie malnutrition on peripheral nerves. A clinical, electrophysiological and histopathological study.

Forty-three children (aged 7 to 62 months) with protein calorie malnutrition (PCM) were studied; 13 had mild to moderate PCM and 30 severe PCM. A reduction of motor nerve conduction velocity and abnormalities of sensory conduction were present in both groups. The abnormality of motor nerve conduction was directly related to the severity of PCM and the presence of hypotonia and/or hyporeflexia. Sural nerve biopsies from both groups were studied for myelinated fibre density, fibre size spectrum, relationship of internodal length with diameter and qualitative light microscopic changes. The biopsies from children with mild to moderate PCM were characterized by a normal developmental change in myelinated fibres with an increasing proportion of medium and large size fibres, a transition from a unimodal to a bimodal distribution and an appropriate relationship of internodal length to fibre diameter. Evidence of mild segmental demyelination was observed in only one patient of this group. In contrast, in the biopsies from children with severe PCM, the normal developmental pattern for myelinated fibre size distribution was impaired with a persistence of small myelinated fibres, and there was a failure of internodal segments on large fibres to elongate with increase in age and significant segmental demyelination in about 50 per cent of cases. Retarded myelination and segmental demyelination probably form the morphological basis for impaired peripheral nerve function in PCM. Short internodes on large diameter fibres may also contribute to this effect.

The density of myelinated fibres is related to the fascicle diameter in human superficial peroneal nerve: Statistical study of 41 normal samples

The density of myelinated fibres in the superficial peroneal nerve was studied in 41 samples from 24 control human subjects. Photographic montages of the whole nerve fascicle were made from semithin and ultrathin transverse sections and used for a statistical analysis of sampling procedures, range of variations and relations between density and other variables. The results indicate that the spatial distribution of myelinated fibres within a nerve is often non-uniform. Therefore, it was not possible to define a statistically valid sampling system. The study of relations between variables shows the lack of any correlation between density and age and a considerable variation in the density. In contrast, there is a strong positive linear correlation between the surface area of the nerve fascicle and its content of myelinated fibres. That is, the fibre density of a given normal nerve is related to its diameter and can be predicted within a narrow range of error. We propose the term “derived density” for this value, and its application as a tool in the diagnosis of peripheral neuropathies is now being studied.