A morphologic-etiologic classification of diseases of the peripheral nerves (peripheral neuropathy).
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Characterization of the sprouting response of axon-like processes from retinal ganglion cells after axotomy in adult hamsters: a model using intravitreal implantation of a peripheral nerve.
Peripheral nerves provide a favourable environment for damaged CNS axons to sprout and regenerate. It has also been demonstrated that retinal ganglion cells respond to a peripheral nerve segment grafted to the retina by emitting axon-like processes from the somatodendritic compartment into the graft. The factors influencing the pattern of sprouting of axotomized retinal ganglion cells were explored in this study by implanting a short segment of peripheral nerve, which did not come into contact with the retina, into the vitreous body of an eye whose optic nerve was concurrently crushed. Silver staining was used to assess the morphology of the retinal ganglion cells which underwent sprouting. Some retinal ganglion cells were induced to sprout axon-like processes; these emerged primarily from dendrites and less frequently from the soma or intraretinal axon. Implantation of a nonviable graft (freeze-thawed) elicited only minimal sprouting. These results suggest that diffusible factors secreted by cells in the graft are a possible stimulus to sprouting in axotomized retinal ganglion cells. Examination of the pattern of dendritic sprouting indicates that sprouting was most intense (in terms of number of sprouts per cell) at early times post-axotomy. Moreover, a differential pattern of development of sprouts arising from individual primary dendrites of the same cell was observed; sprouts tend to arise from all primary dendrites initially but as the post-axotomy time increased, retraction of sprouts from some primary dendrites occurred. Concomitant with this retraction, however, there was an increase in the number of sprouts on those primary dendrites which were still in the active phase of sprouting. Selective stabilization of sprouts by extrinsic factors may account for this phenomenon. Changes in the area and outline (irregularity) of the somata of retinal ganglion cells with sprouts from two weeks to two months after optic nerve crush could be correlated temporally with the intensity of sprouting from the dendritic tree, suggesting that during sprouting, intrinsic mechanisms coordinate the responses of different cellular compartments. In contrast to extensive ectopic sprouting of axotomized retinal ganglion cells in the presence of an intravitreal graft, when a long peripheral nerve segment is grafted to the cut optic nerve, there is extensive axonal regeneration into the graft from retinal ganglion cells, most of which did not exhibit ectopic sprouting. Thus, a hierarchy of sprouting sites within a neuron seems to exist, with the damaged axonal tip being the most favoured site, followed by the dendrites, and then the intraretinal axon.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Intact sciatic myelinated primary afferent terminals collaterally sprout in the adult rat dorsal horn following section of a neighbouring peripheral nerve.
Peripheral nerve section induces sprouting of the central terminals of axotomized myelinated primary afferents outside their normal dorsoventral termination zones in lamina I, III, and IV of the dorsal horn into lamina II, an area that normally only receives unmyelinated C-fiber input. This axotomy-induced regenerative sprouting is confined to the somatotopic boundaries of the injured nerve in the spinal cord. We examined whether intact myelinated sciatic afferents are able to sprout novel terminals into neighbouring areas of the dorsal horn in the adult rat following axotomy of two test nerves, either the posterior cutaneous nerve of the thigh or the saphenous nerve. These peripheral nerves have somatotopically organized terminal areas in the dorsal horn that overlap in some areas and are contiguous in others, with that of the sciatic central terminal field. Two weeks after cutting either the posterior cutaneous or the saphenous nerve, intact sciatic myelinated fibers labelled with the B fragment of cholera toxin conjugated to horseradish peroxidase (B-HRP) sprouted into an area of lamina II normally only innervated by the adjacent injured test nerve. This collateral sprouting was strictly limited, however, to those particular areas of the dorsal horn where the A-fiber terminal field of the control sciatic and the C-fiber terminal field of the injured test nerve overlapped in the dorsoventral plane. No mediolateral sprouting was seen into those areas of neuropil solely innervated by the test nerve. We conclude that intact myelinated primary afferents do have the capacity to collaterally sprout, but that any resultant somatotopic reorganization of central projections is limited to the dorsoventral plane. These changes may contribute to sensory hypersensitivity at the edges of denervated skin.
Afferent Pathways↗
Presence of long and short dystrophin and/or utrophin products in Torpedo marmorata peripheral nerves.
Peripheral nerves from rabbit and Torpedo marmorata were comparatively analyzed for the presence of short dystrophin products. Western blot analyses of Torpedo marmorata peripheral nerve extracts revealed the existence of three proteins belonging to the dystrophin family: a M(r) 400 kDa protein band detected with dystrophin/utrophin, dystrophin-specific and Torpedo utrophin-specific antibodies, a molecule identified as Dp116 and, for the first time at the protein level, a new protein probably corresponding to Up116. All of these products were carefully identified according to the specificities of the monoclonal antibodies used. In immunofluorescence studies, clear staining of the thin rim surrounding each Schwann cell-axon unit was observed in both Torpedo marmorata and rabbit peripheral nerves, showing colocalization of all of these molecules. Their potential functions were discussed in comparison to similar products found in rabbit peripheral nerves.
Animals↗
Evaluation and therapy after injury to peripheral nerves.
Peripheral nerve injuries from whatever cause should be classified according to the degree of axon, fascicle, and main nerve trunk damage. This approach is useful in assessing the chances for spontaneous recovery and planning for surgery directed at improving neural recovery. Evaluation over time may be required to better classify the degree of injury. Once recovery slows or ceases, the surgical approaches available include neurolysis, nerve repair, nerve transposition, autograft reconstruction, and various procedures directed at painful neuromata. With proper mobilization and protection of neural and vascular structures, even extensive orthopaedic reconstructive procedures may be performed. Ischemic neuritis and myopathies may be improved by such combined approaches.
Humans↗
Basic pathology of the peripheral nerve.
Peripheral nerve pathology encompasses a complex array of disease processes that are poorly understood. This article provides a substrate for communication between pathologists and radiologists who are involved in the diagnosis and treatment of patients with peripheral neuropathy. The article is organized into sections on normal histology, routine morphologic techniques used in the study of peripheral nerve, and the basic disease patterns, followed by a brief discussion of selected neuropathies.
Axons↗
Lesion-induced changes in the production of newly synthesized and secreted apo-E and other molecules are independent of the concomitant recruitment of blood-borne macrophages into injured peripheral nerves.
Peripheral nerve injury produces Wallerian degeneration characterized by a change in the composition of resident nonneuronal cells: macrophages are recruited from the circulation to join Schwann, fibroblast, and endothelial cells. At the same time, the nonneuronal cell population exhibits, as a whole, alterations in synthesis and secretion of diffusible molecules, some of which are instrumental in nerve repair mechanisms. In this study, we determined whether changes in the production of secreted molecules depend on the concomitant modification in cell composition. Therefore, we studied the secretion of newly synthesized molecules by defined cell populations of intact nerves, intact nerve explants undergoing in vitro axonal degeneration, in vivo degenerating nerves, and recruited cells. Nerves were incubated in serum-free, [35S]methionine-containing media. Secreted, radioactively labeled proteins were precipitated from the medium and analyzed by gel electrophoresis. Reduced production of 43-, 46-, and 48-kDa proteins and increased production of 33-34-, 37-, 49-, 59-, and 67-kDa proteins were detected in in situ degenerating nerves. High-density ultracentrifugation and immunoblot analysis revealed that the 33-34-kDa protein is apolipoprotein-E (apo-E). Similar alterations in the production of these molecules were detected in intact nerve explants from which blood-borne cells were excluded. Apo-E, 37-, 49-, 59-, and 67-kDa proteins were also produced in frozen nerves that lacked the intact nerve nonneuronal cell population. Instead, these preparations contained blood-borne cells, primarily macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
Ammonium Chloride↗
Epithelial membrane antigen expression by the perineurium of peripheral nerve and in peripheral nerve tumours.
Specimens of normal peripheral nerve and a series of peripheral nerve lesions have been immunostained with three different anti-epithelial membrane antigen (EMA) monoclonal antibodies. Sites of EMA immunoreactivity have been confirmed within perineurial cells of peripheral nerve, noted within the capsule of Schwannomas and palisaded encapsulated neuromas, and also detected with traumatic neuromas and plexiform neurofibromas. No expression was detected within simple neurofibromas, diffuse neurofibromas or within malignant Schwannomas. These sites of EMA expression concur with the suggested involvement of perineurial cells in the formation of the particular lesions. The relationship between EMA expression by the perineurium and the piaarachnoid membrane is discussed.
Antibodies, Monoclonal↗
[Effects of adriamycin on axotomized neurons in regeneration chamber model of the peripheral nerve].
Peripheral nerve tubulization is mainly used to study regeneration. We used this model to study the effects of adriamycin on axotomized dorsal root ganglion neurons after local administration of this drug in silicone chambers placed on the proximal stump of a sectioned nerve. No massive neuronal degeneration has been detected in the dorsal root ganglia. However, adriamycin induced a significant atrophy in axotomized neurons. Our observations indicate that this effect is due to blood borne transport of adriamycin, rather than retrograde axonal transport, and that it affects also axotomized neurons that are not directly exposed to adriamycin at the sectioned stump of their axon.
Animals↗
Comparison of insulated and uninsulated needles for locating peripheral nerves with a peripheral nerve stimulator.
This study was designed to compare the use of insulated and uninsulated needles with a peripheral nerve stimulator for locating a peripheral nerve in an anesthetized cat. The needles were mounted on a one-dimensional manipulator and both the saphenous and sciatic nerves were located. The tip of the insulated needle was consistently placed on the sciatic nerve. The tip of the uninsulated needle was placed 0.1-0.9 cm past the sciatic nerve. Injecting saline to assess the position of the tip of the needle relative to the sciatic nerve did not detect the needle being past the nerve. With the saphenous nerve preparation, both the needle and nerve were visible through the tissue. Using an insulated needle, the minimum current required to stimulate the nerve occurred when the tip of the needle touched the saphenous nerve. Using an uninsulated needle, the minimum current occurred when the tip was 0.1-0.8 cm past the nerve. The conclusion is that insulated needles more precisely locate the peripheral nerve than uninsulated needles.
Animals↗
Mechanical properties of peripheral nerves.
Peripheral nerve trunks are viscoelastic tissues with unique mechanical characteristics. Tensile strength, which includes elastic limit and mechanical failure, concerns surgeons. This study shows that measurements of the load necessary to achieve certain elongations on specimens outside the body do not correspond with in situ measurements. The necessary load is influenced by the presence or absence of branches and by the amount of fibrosis. Because of transverse contraction, elongation beyond a certain limit substantially decreases intrafascicular volume, leading to increased intrafascicular pressure. Stress relaxation is effective only if the nerve repair site is maintained under constant tension. Its beneficial effect disappears after 10 minutes if the repaired nerve is returned to a relaxed state. Therefore, tension at the repair site should be minimized.
Biomechanical Phenomena↗
Infection of armadillos with Mycobacterium leprae. Ultrastructural studies of peripheral nerve.
Peripheral nerves of armadillos were studied 16 to 30 months after intradermal or intravenous inoculation with Mycobacterium leprae. Numerous bacilli were found within macrophages, Schwann cells, and perineurial cells; endothelial cells, pericytes and fibroblasts were involved as well. The bacilli were characteristically contained in membrane-limited vacuoles that were interpreted as being phagosomes. Some of the phagosomes contained granular, membranous, and vesicular debris considered to be bacillary degradation products, suggesting that lysosomal activity was present within the phagosomes. Multivesicular bodies, a few of which contained bacilli, were abundant in macrophages and perineurial cells. An unusual proliferation of irregular tubulovesicular profiles was noted, especially in Schwann and perineurial cell cytoplasm, surrounding and within phagosomes containing bacilli. The pattern of cellular involvement of neural structures with M leprae was similar to that observed in lepromatous leprous neuritis in humans.
Animals↗
Development of nodal and paranodal membrane specializations in amphibian peripheral nerves.
Peripheral nerves from the hind legs of frog tadpoles were examined in order to ascertain the pattern of development of nodal and paranodal specializations in myelinated fibers. In thin sections the earliest detectable node-related specializations resemble "intermediate" junctions between axons and Schwann cell processes. These occur in individually ensheathed axons near the edges of the sheath segments and could represent early nodal or paranodal components or transient structures. The characteristic nodal "undercoating" is indistinct and highly variable in thickness in immature fibers and its density is lower in developing nodes than in adult nodes. Corresponding freeze-fracture replicas of developing axons demonstrate aggregates of nodal E face particles whose concentration is lower than that in the adult. Such aggregates usually occur immediately adjacent to Schwann cell indentations, even though early in development the latter may not exhibit the paracrystalline pattern seen in the adult paranodal axolemma. On rare occasions, node-like particle aggregates and presumptive nodal undercoatings have been observed without recognizable paranodal junctions or indentations nearby. However, neither specialization has been found in axons not individually ensheathed by Schwann cells. Paranodal Schwann cell loops are widely separated and irregularly arranged in the developing nodes, and the paranodal regions flanking a node usually mature asymmetrically. Differentiated paranodal junctions appear early in axons ensheathed by only a few loose Schwann cell lamellae. However, such junctions are not formed by all paranodal loops; they consistently appear first in the loops close to the node and only later in those further removed. No junctional specialization has been observed in either the axolemma or the Schwann cell membrane without the close association of the other.
Aging↗
[Influence of blockades with local anesthetics on the stimulation ability of a nerve by peripheral nerve stimulation. Results of a randomized study].
In the present study we examined the influence of local anesthetics on the ability to stimulate a nerve by means of peripheral nerve stimulation. In 35 patients either 5 ml saline (group 1, n=18) or local anesthetics (group 2, n=17) were injected close to the sciatic nerve in a randomized and double-blind manner. The current needed to stimulate the nerve was measured 30 s and 2 min after injection. The results showed that 30 s and 2 min after injection of local anesthetics there is a strong local anesthetic effect. Therefore nerve damage might occur despite the use of peripheral nerve stimulation. Thus, the multiple injection technique in a close anatomical area has to be considered critically, because anesthetized or partially anesthetized nerves have a lower stimulating ability and could be damaged by a second or third puncture.
Anesthetics, Local↗
A skin blister method to study epidermal nerves in peripheral nerve disease.
Skin is a reservoir of sensory and autonomic nerve fibers that are potential indicators of peripheral nerve disease. Biopsies of skin have shown that sensory nerves in the most superficial layer of skin, the epidermal nerve fibers (ENFs), are reduced in patients with polyneuropathy. This report describes a minimally invasive skin blister method to isolate, image, and obtain quantitative analysis of ENFs. Blisters are made by applying a suction capsule to skin. The epidermal roof of the blister is excised, immunostained, whole mounted, and analyzed for ENF number and distribution. A reduction in number and abnormal distribution of ENFs are early indicators of peripheral nerve disease. Illustrations of skin blister and skin biopsy specimens from patients with different types of peripheral nerve disorders are included. These patients were chosen because their findings demonstrate the complementary information obtained by the blister and biopsy methods and the potential of the blister procedure to evaluate single nerve lesions and polyneuropathy and to follow the progress of ENF degeneration and regeneration.
Adult↗
Diseases of the peripheral nerves.
Peripheral nerve disorders involving the bovine thoracic and pelvic limbs are presented. Anatomic considerations, etiologic mechanisms, clinical signs, diagnosis, and prognosis are detailed for each specific impairment. Treatment, although generally supportive, is also discussed.
Animals↗
Differential regulation of fibroblast growth factor (FGF)-2 and FGF receptor 1 mRNAs and FGF-2 isoforms in spinal ganglia and sciatic nerve after peripheral nerve lesion.
To study the functional role of endogenous basic fibroblast growth factor-2 (FGF-2) during degeneration and regeneration of the sensory system, we have determined the expression and regulation of FGF-2 and FGF receptor (FGFR)-1 mRNAs in spinal ganglia and sciatic nerve during experimental transection and crush injury of the sciatic nerve. In contrast to levels of the FGFR-1 transcript, which is not altered, the level of FGF-2 mRNA is dramatically up-regulated in spinal ganglia after injury. In the proximal and distal nerve stumps both transcript levels are significantly elevated, albeit at different time points. The FGF-2 isoforms are differently up-regulated in spinal ganglia and sciatic nerve following peripheral nerve lesion. The differential response of FGF-2 mRNA and protein and of FGFR-1 mRNA in spinal ganglia and sciatic nerve after lesion is suggestive of different physiological functions: a local reaction at the lesion site where axonal regrowth occurs and a trophic reaction for the degenerating/regenerating sensory neurons.
Animals↗
A canine peripheral nerve sheath tumor including peripheral nerve fibers.
Peripheral nerve sheath tumor was found in a 7-year-old male mongrel dog. The tumors were located in the right cheek subcutis and oral submucosa. Histologically, neoplastic cells were arranged in streaming bundles, occasionally interlacing bundles or whorls of elongated and spindle cells. Cellular atypia was poor and mitotic figures were rarely observed. Ultrastructurally, neoplastic cells had basement membrane, typical of Schwann cells. One bundle of normal peripheral nerve fibers and some myelinated axons were seen within the tumor tissues. Immunohistochemically, neoplastic cells reacted to vimentin, glial fibrillary acidic protein, S-100 protein and neuron specific enolase. In addition to the above immunoreactions, the included nerve fibers were positive for myelin basic protein and neurofilament protein. This paper also discusses immunohistochemical findings on differential diagnosis in comparison with those of canine hemangiopericytomas reported hitherto.
Animals↗