Expression Of Cytokeratin 18 In The Peripheral Nerves

The perineurium constitutes the basis for the regulation of endoneurial fluid homeostasis. In the work presented here, cytokeratin 18, as an immunohistochemical marker for epithelial cells, was used to identify the perineurium in the peripheral nerves of two species. Two organs, rich in peripheral nerves, were used; the tongue of the bull and the ductus deferens of the male goat. Special attention was paid to one of the the nerve sheath cells - the perineurial cells of myelinated nerves in the skeletal muscle of the tongue and in the smooth muscle in the wall of the ductus deferens. A positive reaction to cytokeratin 18 was found in the perineurial cells of the perineurial sheath in the nerves of various sizes. No difference in the reactivity was observed between the peripheral nerves of the tongue and that of the ductus deferens.

Sox10 is required for Schwann cell identity and progression beyond the immature Schwann cell stage

Mutations in the transcription factor SOX10 cause neurocristopathies, including Waardenburg-Hirschsprung syndrome and peripheral neuropathies in humans. This is partly attributed to a requirement for Sox10 in early neural crest for survival, maintenance of pluripotency, and specification to several cell lineages, including peripheral glia. As a consequence, peripheral glia are absent in Sox10-deficient mice. Intriguingly, Sox10 continues to be expressed in these cells after specification. To analyze glial functions after specification, we specifically deleted Sox10 in immature Schwann cells by conditional mutagenesis. Mutant mice died from peripheral neuropathy before the seventh postnatal week. Nerve alterations included a thinned perineurial sheath, increased lipid and collagen deposition, and a dramatically altered cellular composition. Nerve conduction was also grossly aberrant, and neither myelinating nor nonmyelinating Schwann cells formed. Instead, axons of different sizes remained unsorted in large bundles. Schwann cells failed to develop beyond the immature stage and were unable to maintain identity. Thus, our study identifies a novel cause for peripheral neuropathies in patients with SOX10 mutations.

A substantial part of GLUT-1 in crude membranes from muscle originates from perineurial sheaths

The distribution of GLUT-1 and GLUT-4 in cryosections of rat skeletal muscles was investigated immunocytochemically. Intense labeling of GLUT-1 was found in the perineurial sheaths of intramuscular nerves, whereas only a very faint signal was associated with the sarcolemma, and labeling of extraneural vessels was not detectable. The majority of the GLUT-4 reactivity was located at the periphery of muscle cells in nonuniform patches, and GLUT-4 was absent in vessels and nerves. In sections of femoral nerve GLUT-1 was confined to the perineurial sheath and endoneurial vessels. The contribution of GLUT-1 from intramuscular perineurial sheaths to total GLUT-1 in a muscle was determined from immunoblots of crude membranes isolated from mixtures of homogenates of excised nerves and muscles. The recovery of GLUT-1 increased linearly with the amount of nerve added, and it was calculated that GLUT-1 from intramuscular perineurial sheaths accounted for approximately 60% of the GLUT-1 content in a membrane fraction from soleus muscle or red gastrocnemius. The remaining 40% of GLUT-1 is likely to originate from the sarcolemma.

Calcium content of frog sciatic nerve during chronic hypocalcemia and hypercalcemia

We examined the calcium contents of desheathed peripheral nerve, perineurial sheath, and whole sciatic nerve in the frog as a function of the steady-state plasma concentration of ionized calcium. Chronic hypocalcemia was induced by parathyroidectomy and by bathing frogs in a phosphate medium. Chronic hypercalcemia was induced by administering vitamin D3 and by bathing frogs for up to 2 wk in medium containing 50 mM CaCl2. Calcium was measured with a calcium-sensitive electrode and by atomic absorption spectroscopy. The calcium contents (mmol/kg wet wt) in whole nerve, desheathed nerve, and the perineurial sheath varied linearly with slopes of 0.72, 0.71, and 1.72, respectively, with plasma concentration (mM) of ionized calcium, which ranged from 0.3 to 8.0 mM. In the same animals the calcium content in the cerebrum was independent of plasma calcium between 0.5 and 1.5 mM but rose at higher plasma concentrations. Our results indicate that net calcium concentration in the frog peripheral nerve is not regulated during chronic hypocalcemia and hypercalcemia, whereas brain calcium is regulated at plasma calcium concentrations less than 1.5 mM. The lack of calcium regulation in the nerve is attributed to the lack of calcium regulation in the endoneurial compartment.

Dermal nerves in monzygotic twins discordant for diabetes: Morphometric study of perineurial cell basement membrane

Nerves in the dermal layer of skin are typically composed of several myelinated and unmyelinated nerve fibers surrounded by a perineurial sheath. Generally, this sheath is composed of one to two perineurial cell layers. The perineurial sheath helps to maintain a suitable environment for proper nerve function (1) and morphological changes in the sheath may cause nerve dysfunction (2). Perineurial cell basement membrane (PCBM) becomes thickened in diabetics and this phenomenon has been viewed as a diagnostic aid in the detection of diabetes (3). Since other factors (e.g. genetics, aging, vascular disease) may play a role in basement membrane morphology, we undertook this study of dermal nerves from identical twins discordant for diabetes to determine the effects of diabetic dysmetabolism on morphological changes in the PCBM. Since monozygotic twins have an identical genetic composition, it is likely that any significant differences in the dermal nerve would be due to factors related to diabetes.

Regional variation in perineurial cell basal lamina thickness in nerves of diabetics

The perineurial sheath, composed of multiple layers of perineurial cells, plays an important role in maintaining an optimal endoneurial environment. Alterations in the perineurial sheath have an effect on nerve function and may play a role in the formation of neuropathy. Neuropathy is a common complication of diabetes mellitus (DM). Perineurial cell basal lamina (PCBL) thickening is associated with the diabetic syndrome and the degree of thickening is correlated with the duration of diabetes. The process of basal lamina (BL) thickening in capillaries as well as perineurial cells has been the subject of numerous studies. Some investigators have suggested that the process of BL thickening is directly related to altered metabolism, e.g. hyperglycemia. If hyperglycemia is directly related to PCBL thickening in the nerves of diabetics, it is likely that the degree of BL thickening would be relatively uniform thoughout the peripheral nervous system (PNS).

Calcium efflux from amphibian sciatic nerve

Eight Xenopus laevis were injected intraperitoneally with 45CaCl2 and 16–18 h later an unbranehed section from each sciatic nerve was removed. Efflux measurements of nerve from which the perineurial sheath had been removed could be described by three compartments of approximately eqvial size with half-lifes of 2.37 ± 0.76 (SD), 30.3 ± 17.3, and 196 ± 61 min, the shortest lived compartment representing diffusion from the extracellular space with a coefficient of diffusion of 2.1 ± 0.7 × 10−6 cm2/s. Efflux from nerve in which the perineurium remained intact was characterized by a half-life of 862 ± 399 min resulting from the sheath acting as a diffusion barrier of permeability 3.4 ± 1.6 × 10−7 cm/s. The perineurium was found to bind or sequester a quantity of calcium 1–2 times that contained in an equal volume of plasma.

Histopathological changes following removal of the perineurium

✓ Using microsurgical techniques, the perineurial sheath was stripped off the sciatic nerves of rats over a 0.5 cm length at a point where the nerve consists of a single fascicle. The nerves were excised 0 to 84 days after the injury, and were examined in semi-thin transverse section. A new sheath, closely resembling normal perineurium, became organized during the first 10 days; it appeared uniformly over the length of the injured segment. The new perineurial sheath was probably formed by endoneurial fibroblasts migrating from within the fascicle. In undamaged specimens, the axons immediately beneath the excised perineurium underwent no degenerative changes.