Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DEMYELINATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed1991

Transplanted type-1 astrocytes facilitate repair of demyelinating lesions by host oligodendrocytes in adult rat spinal cord.

The ethidium bromide model of demyelination/remyelination provides a system for studying the interactions between demyelinated axons, host glia and transplanted glia. The injection of 0.1% ethidium bromide in isotonic saline into the white matter of the spinal cord produces a glia-free demyelinating lesion which is subsequently remyelinated by Schwann cells and, to a lesser extent, oligodendrocytes. the in vitro description of an oligodendrocyte progenitor isolated from the adult CNS, together with the recognized role of type-1 astroctyes in controlling the developmental programme of perinatal O-2A progenitors, suggested the possibility that transplanted type-1 astrocytes may potentiate oligodendrocyte remyelination of the ethidium bromide lesion. Purified type-1 astrocyte cultures were prepared by removing cells of the oligodendrocyte lineage using a combination of exposure to cytosine arabinoside and complement-mediated immunocytolysis. Following transplantation of purified type-1 astrocyte cultures into ethidium bromide lesions, a significant increase in the extent of oligodendrocyte remyelination was achieved. Because the purified type-1 astrocyte cultures had no demonstrable oligodendrocyte-generating potential it was concluded that the additional oligodendrocytes appearing in the type-1 astrocytes transplanted lesion were of host origin. These results indicate that type-1 astrocytes can facilitate repair of demyelinating lesions by host oligodendrocytes. The possible mechanisms whereby this facilitation occurs are discussed.

Animals↗
PubMed1986

The anterior medullary velum and its involvement during autoimmune demyelination.

The anterior medullary velum (AMV), a thin lamina of central white matter forming the roof of the IVth ventricle, has been analysed ultrastructurally in the normal guinea pig and in guinea pigs with chronic relapsing experimental allergic encephalomyelitis. In the latter condition, the AMV appeared to provide a route of access for haematogenous elements from the circulation into the ventricular space. The normal AMV consisted of fascicles of myelinated nerve fibres embedded in a layer of highly attenuated ependymal cells. Between the fascicles, the AMV was comprised merely of a layer of ependymal cytoplasm, in places about 0.5 micron thick. In contrast to ependymal cells from other levels of the neuraxis, in ependymal cells in the AMV, ciliary rootlets of the basal body apparatus were extraordinarily long, numerous and prominent. Their prominence might be related to a need for increased flexibility in this region of the ventricular system. Despite previous claims to the contrary, nerve cell bodies were present within the AMV as well as many synaptic complexes, unmyelinated axons, and supra- and subependymal axons believed to belong to the serotoninergic plexuses. During autoimmune demyelination, the meningeal space over the AMV became heavily infiltrated, inflammatory cells entered the nerve fibre bundles, myelin was destroyed and, perhaps related to disruption of the ependymal layer in places, haematogenous macrophages gained access to the ventricular surface of the AMV. Clinical relapses were accompanied by renewed inflammatory and demyelinative activity and further attenuation of the AMV with concomitant fibrous astrogliosis. Thus the AMV is described in detail for the first time at the ultrastructural level and is presented as a region vulnerable during periods of meningeal infiltration. The cytoarchitecture of the AMV might contribute to the genesis of demyelinated plaques around the IVth ventricle.

Animals↗
PubMed1993

Combined central and peripheral acute demyelination.

We describe a patient with multiple sclerosis who had a bout of central demyelination associated with an acute inflammatory demyelinating polyneuropathy. The contemporary involvement of central and peripheral nervous system due to a demyelinating disease has been reported anecdotically in humans, and can be induced experimentally in animals. It may be sustained by a common pathogenetic factor.

Adult↗
PubMed1994

Central nervous system demyelinating diseases and increased release of cholesterol into the urinary system of rats.

The question of what happens to cholesterol in the adult central nervous system during its slow turnover has been addressed using rats with brain and spinal cord labeled with [4-14C]cholesterol upon intracerebral injection of labeled cholesterol into rats at 10-12 days of age. At six months after injection, 14C was found only in the brain and spinal cord and was slowly released via the rat's urine. When labeled rats were given demyelinating agents (triethyl tin chloride, hexachlorophene, sodium cyanide) and when experimental allergic encephalomyelitis was induced, a measurable increase in urinary 14C label above control levels was found. It was concluded that there is a direct relationship between the experimental demyelination induced and the increased release of cholesterol metabolites into urine. The study suggests that a clinical method could be developed to determine the rate of central nervous system demyelination by measuring the amount of urinary cholesterol metabolites.

Animals↗
PubMed1996

Severe cranial nerve involvement in longstanding demyelinating polyneuropathy: a clinicopathologic correlation.

Onion bulb formations involving cranial nerves are an unusual pathologic feature. We report the postmortem neuropathologic findings in a 69-year-old man with a longstanding neuropathy characterized by progressive muscle weakness, sensory ataxia and multiple cranial nerve abnormalities. Electrodiagnostic testing disclosed features of an acquired demyelinating polyneuropathy. Treatment with corticosteroids and plasmapheresis resulted in no change in his neurologic status, and the patient died after repeated episodes of pneumonia and sepsis. Autopsy showed widespread onion bulb formation in cranial nerves III, IV, V, VI, X, XI and XII, anterior and posterior spinal nerve roots, dorsal root ganglia and multiple peripheral nerves, some of which also had foci of epineurial perivascular inflammation. Muscle sections revealed severe neurogenic atrophy. This case demonstrates that, in longstanding acquired demyelinating neuropathy, the cranial nerves also undergo repetitive cycles of demyelination and remyelination resulting in severe weakness of the bulbar musculature and histologic features of hypertrophic neuropathy.

Aged↗
PubMed1998

Systemic complement depletion reduces inflammation and demyelination in adoptive transfer experimental allergic neuritis.

The effect of systemic complement depletion by cobra venom factor (CVF) was evaluated in adoptive transfer experimental allergic neuritis (AT-EAN). Spleen cells of rats immunized with a neuritogenic peptide SP26 were injected into naive rats. On days 3 and 6 after cell transfer AT-EAN rats were treated with CVF or saline intraperitoneally. AT-EAN rats treated with CVF had significantly lower scores for histological inflammation (0.25 +/- 0.25 vs 1.9 +/- 0.4, mean +/- SEM, P < 0.03) and demyelination (0.13 +/- 0.13 vs 1.6 +/- 1.4, P < 0.02) than saline-treated AT-EAN rats. Immunocytochemistry of lumbosacral nerve roots showed significantly less ED1-positive macrophages (0.5 +/- 0.3 vs 1.6 +/- 0.6, P < 0.04) and CD11bc-positive (expressing complement receptor 3 or CR3) inflammatory cells (0.6 +/- 0.4 vs 1.7 +/- 0.5, P < 0.03). Our data suggest that complement plays a crucial role in inflammatory demyelination since systemic complement depletion significantly reduces recruitment of macrophages into the nerve and subsequent macrophage-mediated demyelination.

Animals↗
PubMed1998

Focal lesions area feature of chronic inflammatory demyelinating polyneuropathy (CIDP).

In a study designed to identify the neuropathological features typical of chronic inflammatory demyelinating polyneuropathy (CIDP), we reviewed the sural nerve biopsy findings in 105 patients with this disorder. The patients' mean age at biopsy was 49 years. In 65% of patients the disease had a progressive and in 35% a relapsing-remitting course. In 47% of cases the disorder was idiopathic; the remainder had various concurrent conditions. All sural nerve biopsy specimens showed varying amounts of active demyelination associated with onion bulbs (48% of cases), endoneurial edema (55%) and inflammatory infiltrates (25%). The immunopathological hallmarks were T cell infiltration with macrophagic activation and up-regulation of major histocompatibility complex (MHC) class II expression, without B cell infiltration or immunoglobulin deposition on myelin sheaths. In 30% of cases some myelin sheaths showed C3d deposition. Analysis of proinflammatory cytokine expression invariably showed interleukin-1 in perivascular and endoneurial ramified cells and tumor necrosis factor-alpha prevalently in epineurial macrophages, whereas it detected interferon-gamma only in samples with perivascular inflammatory cells. This immunological pattern suggests that the cellular components of immunity play the major role in CIDP. In 19% of cases the neuropathological changes had a focal distribution. This distinctive feature corresponded to more active demyelination, more frequent detection of inflammatory infiltrates and more prominent immunological activation, suggesting that focal involvement is a possible step in the course of the disease.

Adolescent↗
PubMed2005

The pathology of multiple sclerosis is the result of focal inflammatory demyelination with axonal damage.

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system manifested morphologically by inflammation, demyelination, axonal loss and gliosis. The inflammatory lesions are characterized by massive infiltration by a heterogeneous population of cellular and soluble mediators of the immune system, including T cells, B cells, macrophages and mi croglia, as well as a broad range of cytokines, chemokines, antibodies, complement and other toxic substances. The appearance of such lesions is associated with clinical relapses. Recent detailed immunopathological studies of early, acute lesions revealed profound heterogeneity in the patterns of demyelination and the factors of the immune system involved. During remission, resolution of inflammation is the main factor which leads to clinical improvement of patients. However, the immune system can play a beneficial role at this stage, promoting remyelination perhaps by production of growth factors such as BDNF. In contrast, the progressive irreversible neurological deficit in multiple sclerosis is associated with neurodegenerative processes resulting in axonal and neuronal loss. The mechanisms behind damage to axons in multiple sclerosis lesions are poorly understood. However, the close proximity of areas with prominent axonal loss and areas containing inflammatory infiltrates (e. g., T cells, macrophages) suggest that axonal damage is closely associated with inflammation. Different soluble or cellular mediators of the immune response have been shown to damage axons in experimental systems, and these may be responsible for neurodegeneration in human disease.

Amyloid beta-Protein Precursor↗
PubMed2004

Monofocal acute large demyelinating lesion mimicking brain glioma.

We report the case of a 34-year-old woman with clinical, neuroradiological and intraoperative histological findings, suggesting a low-grade astrocytic tumour. The demyelinating nature of the lesion was established through biopsy only after neurosurgery. The lesion size, in fact, greatly exceeded that of the perivenous demyelination seen in typical multiple sclerosis (MS) and tended to present as a space-occupying mass. This case underlines the importance of considering demyelinating isolated lesions in the differential diagnosis of a brain mass. Since misdiagnosis can result in unwarranted and aggressive therapy, it is critical for the neurologist to be aware of this serious diagnostic pitfall.

Adult↗
PubMed2006

Spreading of autoimmunity from central to peripheral myelin: two cases of clinical association between multiple sclerosis and chronic inflammatory demyelinating polyneuropathy.

Demyelinating inflammatory diseases of central and peripheral myelin share similar aetiopathogenesis but rarely occur simultaneously in the same individual. Here we report two clinical cases of temporal association between multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Our finding supports the hypothesis that clinically manifested central and peripheral demyelinating diseases could result from a common pathogenic event characterised by T-cell autoimmunity spreading from central to peripheral myelin.

Autoimmunity↗
PubMed2003

The role of nonconventional magnetic resonance imaging techniques in demyelinating disorders.

The use of nonconventional magnetic resonance imaging techniques (eg, magnetization transfer, magnetic resonance spectroscopy, and diffusion weighted imaging) allows for an accurate characterization of lesions as compared with conventional or standard approaches in demyelinating diseases. Magnetization transfer, magnetic resonance spectroscopy, and diffusion weighted imaging have revolutionized our understanding of demyelinating diseases because these techniques have been used to identify pathologic changes of normal-appearing brain tissue and characterize the differences in lesions. Metrics derived from these methods correlate with clinical disability and provide more accurate tools for monitoring disease activity and treatment effect over time. Quantitative T1 and T2 relaxation time maps provide additional information on demyelinating diseases, allowing for the evaluation of myelin water and distribution of water within tissues. Finally, the measurement of central nervous system atrophy has become a valuable element in determining the course of multiple sclerosis.

Atrophy↗
PubMed2005

Stem cell therapy for central nervous system demyelinating disease.

Recent advances in cell-based therapies for demyelinating central nervous system diseases have demonstrated the ability to restore damaged neuronal architecture and function. Demyelinated axons in patients with multiple sclerosis can spontaneously remyelinate over time; however, the rate and extent at which remyelination occurs is inadequate for complete recovery. Previous attempts aimed at regenerating myelin-forming cells have been successful but limited by the multifocal nature of the lesions and the inability to produce large numbers of myelin-producing cells in culture. Stem cell-based therapy can overcome these limitations to some extent and may prove useful in the future treatment of demyelinating diseases.

Animals↗
PubMed1985

Galactocerebroside antiserum causes demyelination of cat optic nerve.

A model of immune-mediated optic nerve demyelination is described. Micro-injection of small volumes (less than 5 microliter) of high titer polyclonal anti-Gal-C serum into the cat optic nerve resulted in a focal, highly selective demyelinative lesion followed by remyelination. Demyelination appears to be due to a dual effect on myelin and on oligodendrocytes. The numbers of these cells within the lesion were initially reduced but subsequently increased as remyelination occurred.

Animals↗
PubMed1986

Action potential characteristics of demyelinated rat sciatic nerve following application of 4-aminopyridine.

The sciatic nerves of rats were demyelinated by microinjection of lysophosphatidylcholine. A variety of abnormalities such as conduction slowing and block were present. Application of the potassium channel blocker 4-aminopyridine (4-AP) to the lesion site, led to an increase in area of the compound action potential recorded across the site of demyelination. Single axon recordings revealed three types of changes that may account for the 4-AP-induced increase in the compound response. One group showed broadening of the action potential. Other axons showed hyperexcitability following 4-AP, as manifest by spontaneous firing and multiple spike discharge following a single stimulus. In some of the axons studied, 4-AP led to overcoming of conduction block. Although many axons showed increased excitability properties in the presence of 4-AP, the frequency-following ability of the axons was reduced, and the absolute refractory period of the axons was increased. These results indicate that pharmacological blockade of potassium channels with 4-AP not only leads to action potential broadening in demyelinated axons, but to a variety of excitability changes. These heterogeneous effects of 4-AP should be considered in the rationale for its clinical use.

Action Potentials↗
PubMed1986

The relationship between axonal transport of protein and demyelination in the optic nerves of mice infected with Semliki Forest virus.

Fast and slow axonal transport of protein have been studied in the optic nerves of mice infected with Semliki Forest Virus (SFV) that causes patchy demyelination throughout the CNS. Intravitreal injections of [3H]proline were given at regular intervals after virus inoculation, the labelled protein in the superior colliculi was then measured after survival periods of 18 h or 10 days, for fast and slow axonal transport studies, respectively. Fast transport studies showed an enhanced amount of protein arriving at the optic nerve terminals (superior colliculus) of the SFV-infected mice prior to the onset of demyelination. In contrast, the slow transport studies showed an enhanced amount of protein at the superior colliculus of the SFV-infected mice during the demyelination period. There was no concomitant increase in labelled protein in the retina at any time after the SFV infection. It is proposed that alteration in the transport of the protein constituents other than major myelin specific components may cause disruption of myelin maintenance in SFV infection.

Animals↗
PubMed1987

Schwann cells divide in a demyelinating lesion of the central nervous system.

A demyelinating lesion was induced in the rat central nervous system (CNS) by the microinjection of lysophosphatidylcholine into the spinal cord. Animals were given a single dose of tritiated thymidine 6-72 h before perfusion fixation. Correlative light microscope autoradiography and electron microscopy revealed many labeled Schwann cell nuclei that were associated with demyelinated axons in 1-3 week lesions. Myelinating Schwann cells were rarely labeled. The results indicate that Schwann cells proliferate in the CNS. They appear to divide on contact with demyelinated axons and to stop dividing when they form myelin.

Animals↗
PubMed1989

Sodium channels in single demyelinated mammalian axons.

The distribution of ionic channels is thought to play an important role in the recovery of function following demyelination. Rat sciatic nerves were demyelinated by lysolecithin and single fibers were examined with patch clamp techniques. Voltage-dependent sodium currents were measured in both internodal and nodal regions. The results suggested that while there is a sharp gradient in channel density at the node of Ranvier, the total number of internodal channels far exceeds the total number of nodal channels. The nodal channels do not diffuse freely following demyelination and the internodal channels may thus serve important functions as conduction is restored.

Animals↗