Chronic demyelination in mouse peripheral nerve produced by lysophosphatidyl choline and X-irradiation: ultrastructural observations (original) (raw)
Related papers
Remyelination of nerve fibers in the transected frog sciatic nerve
Brain Research, 1990
This project tests an important aspect of the cellular events controlling the processes of recovery of function and remyelination that follow demyelination in the peripheral nervous system. Frog sciatic nerves have been shown to survive and remain functional for up to 10 days following transection 29. We have utilized this property in order to dissociate the recovery process from possible control by the neuronal soma. Xenopus sciatic nerves were demyelinated in one branch by an intraneural injection of lysolecithin. The nerve was cut proximally to the injection site either immediately before, or several days after the lysolecithin injection. Recovery of function and remyelination were then followed by electrophysioiogical, optical, and ultrastructural techniques applied both to whole branches and single fibers. Controls included the cut but uninjected branch, and injected but uncut nerves. The progression of events during both demyelination and recovery in cut axons was indistinguishable from that in uncut fibers. This suggests that this process may be under local control and can be initiated and carried out in the absence of constant communication with the nerve cell body.
Remodelling of internodes in regenerated rat sciatic nerve: electron microscopic observations
Journal of Neurocytology (UK), 1986
Twelve adult rats received a crush lesion of the left sciatic nerve in the upper thigh. Following survival times of 2 weeks to 6 months, the animals were perfused with glutaraldehyde. Longitudinal thin sections from regenerated nerve segments were examined by electron microscopy. At survival periods of 2 weeks to 1 month, exceptionally short internodes composed of a Schwann cell lacking myelin, a more or less wrinkled Schwann cell-myelin sheath unit, or Schwann cell cytoplasm containing lamellated bodies and lipid droplets, were found intercalated between conventional regenerated myelin sheaths. Such intercalated sheaths were always bordered by sites with a nodal differentiation. Although much less frequent, short distorted myelin sheaths were also found at roe times of 2 and 3 months, but they have not been round in sections from 6-month specimens. In the long-terre regenerated nerves many paranodes were distorted by prominent myelin folds and some nodes of Ranvier exhibited abnormal axon-Schwann cell networks and adaxonal Schwann cell protrusions. These observations show that internodes in regenerated rat sciatic nerves are subject to extensive remodelling. This includes intemodal shortening and nodal migration, myelin sheath breakdown and demyelination, elimination of redundant Schwann cells and nodal fusion. These morphological changes rnay have important physiological implications.
Journal of anatomy, 1988
The quantitative relationships between the size of the Schwann cell sheath and that of its related axoplasm were studied by electron microscopy in cross sections of bundles of unmyelinated axons (Remak bundles) of the spinal roots of lizard (Lacerta muralis). It was found that (i) the cross sectional area of the Schwann cell sheath is directly proportional to that of its related axoplasm (correlation coefficient 0.84), and (ii) the ratio between the cross sectional area of the Schwann cell sheath and that of its related axoplasm tends to diminish as the cross sectional area of the latter increases. Thus, under normal conditions, in the bundles of unmyelinated axons of the spinal roots of lizard a quantitative balance exists between the nerve tissue and its associated glial tissue. These results agree with those previously obtained in the myelinated fibres of the same region and in the spinal ganglia of the lizard, gecko, cat and rabbit. Some of the mechanisms probably involved in th...
X-irradiation impairs regeneration of peripheral nerve across a gap
Journal of Neurocytology, 1986
The effects of X-irradiation on the regeneration of peripheral nerve across a gap were studied in the mouse. The right sciatic nerve was transected and 3 days later a 20-Gy dose of X-rays was administered to the hind limb, which was shielded so that the irradiation affected either the proximal, the distal or both parts of the nerve. Within a few hours of irradiation, the proximal and distal nerve stumps were inserted into a polythene tube within which they were separated by a 5-ram gap. After 1 or 2 months the sciatic nerves were processed for examination by light and electron microscopy. Irradiation affected axonal growth, differentiation of Schwann cells and formation of a perineurium. These effects were most marked when both the proximal and distal stumps had been exposed to X-rays. At 2 months there were fewer axons in the irradiated than in control nerves (P < 0.01), but all of the larger axons which had regenerated were myelinated, albeit more thinly than in the controls. The changes in the pattern of regeneration in the irradiated nerves are interpreted as being largely due to radiation damage to Schwann cells.
The effect of the mouse mutation claw paw on myelination and nodal frequency in sciatic nerves
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1998
Despite the biophysical and clinical importance of differentiating nodal and internodal axolemma, very little is known about the process. We chose to study myelination and node of Ranvier formation in the hypomyelinating mouse mutant claw paw (clp). The phenotype of clp is delayed myelination in the peripheral nervous system. The specific defect is unknown but is thought to arise from a breakdown in the complex signaling mechanism between axon and Schwann cell. Myelination was assessed in sciatic nerve cross sections from adult and postnatal day 14 (P14) heterozygous and homozygous clp mice. Antibodies to P0, myelin-associated glycoprotein (MAG), and neural cell adhesion molecule were used to assess the stage of myelination. P14 homozygous clp mice showed an atypical staining pattern of immature myelin, which resolved into a relatively normal pattern by adulthood. Sodium channel clustering and node of Ranvier frequency were studied in whole-mount sciatic nerves with sodium channel a...
Remyelination in the rat dorsal funiculus following demyelination by laser irradiation
Neuroscience Research, 1997
Excimer laser (KrF excimer laser, 248 nm wavelength) was used to damage cellular components in the dorsal funiculus at the lumbar level (L2) of the rat spinal cord. An open lesion was not found at the irradiation site on the spinal cord. However, the cytological examination revealed that cellular components were damaged to the depth of 200 -500 vm from the pial surface. The characteristic feature was that at the border of the lesion, many axons remained naked but intact after their myelin sheaths had been completely disintegrated. Such naked axons were subsequently remyelinated by mature or immature glial cells. Mature oligodendrocytes, while retaining their cytoplasmic processes connected with the myelin sheaths of unaffected axons, extended new cytoplasmic processes on nearby naked axons and made new myelin sheaths around them. In contrast, 7 days after the irradiation, numerous immature glial cells appeared in association with naked axons, and some of them were differentiated into oligodendrocytes forming thin myelin sheaths on naked axons. These findings suggest that demyelinated axons can cause the proliferation and probably dedifferentiation of the oligodendrocyte lineage. The use of lasers provides a unique experimental model of demyelination and remyelination in the central nervous system of adult mammals. © 1997 Elsevier Science Ireland Ltd.
Electron Microscopy Analysis of Sciatic Nerve Fibers in C57BL/6 Transgenic Mice
Neurophysiology, 2020
Hereditary Charcot–Marie–Tooth (CMT) motor/sensory neuropathy is a known disease in the group of polyneuropathies. It is characterized, in particular, by the process of demyelination of peripheral nerve fibers. Various in vivo and in vitro models have been used for elucidation of the mechanisms involved in the demyelination processes. We investigated ultrastructural manifestations of peripheral demyelination in C57BL/6 transgenic mice. Electron microscopic examination of fibers of the sciatic nerve in such mice showed that many axons in this nerve were subjected to dys- and demyelination; the so-called onion bulb-like structures were observed. In some fibers, hypertrophy of myelin sheaths was found. In general, ultrastructural modifications in the sciatic nerve of the C57BL transgenic mice were rather similar to the pathomorphological pattern observed in patients suffering from CMT. Thus, the transgenic heterozygous line of C57BL mice can be used as an adequate model for revealing the mechanisms of development of CMT and for the experimental search of treatments for this disease.
Neuroscience Letters, 2005
Transplantation of myelin-forming cells can remyelinate axons, but little is known of the sodium channel organization of axons myelinated by donor cells. Sciatic nerve axons of female wild type mice were transected by a crush injury and Schwann cells (SCs) from green fluorescence protein (GFP)-expressing male mice were transplanted adjacent to the crush site. The male donor cells were identified by GFP fluorescence and fluorescence in situ hybridization (FISH) for Y chromosome. In nerves of GFP-expressing mice, GFP was observed in the axoplasm and in the cytoplasmic compartments of the Schwann cells, but not in the myelin. Following transplantation of GFP-SCs into crushed nerve of wild type mice, immuno-electron microscopic analysis indicated that GFP was observed in the cytoplasmic compartments of engrafted Schwann cells which formed myelin. Nodal and paranodal regions of the axons myelinated by the GFP-SCs were identified by Na v 1.6 sodium channel and Caspr immunostaining, respectively. Nuclear identification of the Y chromosome by FISH confirmed the donor origin of the myelin-forming cells. These results indicate that engrafted GFP-SCs participate in myelination of regenerated peripheral nerve fibers and that Na v 1.6 sodium channel, which is the dominant sodium channel at normal nodes, is reconstituted on the regenerated axons.