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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary demyelination occurs in a variety of human and experimental diseases known to be associated with the presence of inflammatory cells. However, the mechanism of demyelination remains unclear. The possibility that myelin can be damaged as a nonspecific consequence of a specific delayed type of hypersensitivity reaction directed at nonnervous tissue antigens was investigated. Guinea pigs were sensitized to tuberculin with Freund's complete adjuvant, and were challenged in the central and peripheral nervous system either with live or killed sonicated tubercle bacilli, Old Tuberculin, or tuberculin purified protein derivative (PPD). Local inflammatory reactions were invariably produced and primary demyelination was a constant feature of the lesions. The morphological picture was rather similar to that observed in human neurotuberculosis and early tuberculoid leprosy, and in experimental allergic encephalomyelitis and distemper encephalitis in animals. The infiltrates consisted predominantly of mononuclear cells with some polymorphonuclear cells as well. Vesicular disruption of the myelin sheath in the immediate vicinity of the inflammatory cells and stripping of the myelin lamellae by the histiocytes without axonal damage were the leading features of the lesion. The results indicate that cell-mediated immune reactions to a variety of nonbrain antigens could be responsible for a component of the demyelination seen in some inflammatory demyelinating conditions, and suggest that this system may serve as a useful model for studying the immunopathology of demyelinating disease.
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PMID:Primary demyelination as a nonspecific consequence of a cell-mediated immune reaction. 80 45

The effectiveness of the alpha 1-adrenergic antagonist prazosin for preventing monoaminergic axonal damage in the spinal cords of rats that were inoculated for experimental allergic encephalomyelitis (EAE) was assessed using immunohistochemistry. Prazosin injections (2 mg, i.p.) given twice daily from day 7 to day 15 postinoculation significantly reduced paralysis, spinal cord inflammation and monoaminergic axonal damage compared to saline injections. A close positive correlation between severity of inflammation and severity of axonal damage was found for both prazosin- and saline-treated rats that were inoculated for EAE. These findings confirmed previous observations of suppression of the development of clinical signs of EAE by prazosin treatment and supported the hypothesis that some factor associated with spinal cord inflammation may be responsible for the bulbospinal monoaminergic axonal damage that occurs during EAE.
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PMID:Prazosin suppresses development of axonal damage in rats inoculated for experimental allergic encephalomyelitis. 135 63

A late onset, demyelinating form of experimental allergic encephalomyelitis (EAE) was induced in New Zealand White rabbits following immunisation with a synthetic peptide representing the amino acid sequence 91-110 of bovine myelin proteolipid protein (PLP). Histologically, disease was associated with varying degrees of central nervous system (CNS) inflammation, which in six of seven animals was accompanied by axonal degeneration and secondary demyelination. Primary demyelination with axonal sparing was generally absent in this model of EAE. Immunohistochemical and immunoelectron microscopic analysis of CNS tissue indicate that B cell epitopes within this encephalitogenic PLP sequence are not exposed at the surface of the myelin sheath, but are sequestered within compact multilamellar myelin. Furthermore, no correlation was observed between the anti-PLP antibody titer induced by the peptide and either the clinical severity or histopathology of the disease. These observations suggest that the B cell response to epitopes within the PLP sequence 91-110 does not play a primary role in the immunopathogenesis of PLP-induced EAE.
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PMID:Identification of an encephalitogenic determinant of myelin proteolipid protein for the rabbit. 169 74

Spinal cord monoaminergic and peptidergic axonal damage occurring during the development of experimental allergic encephalomyelitis (EAE) was assessed using immunohistochemistry. Spinal cord axons immunoreactive for serotonin, catecholamines, or a thyrotropin-releasing hormone marker peptide were found to be markedly swollen and distorted by the earliest stage of detectable paralysis during EAE development (the flaccid tail stage). As clinical signs progressed to complete hindlimb paralysis, axonal damage became increasingly extensive. Axonal damage was equally pronounced whether EAE was induced by inoculation with purified myelin basic protein or with whole spinal cord homogenate, suggesting that the damage did not result from an immune attack directed against specific monoaminergic and/or peptidergic antigens present in the inoculant. However, two observations suggested that mechanical or chemical factors associated with the inflammatory foci contribute to the axonal damage: first, distorted axons were nearly always located adjacent to blood vessels or the pial surface, sites at which inflammation occurs during EAE. Second, the severity of axonal damage correlated with the severity of the inflammation. The early onset of axonal damage during development of EAE and the close correlation that was found between the severity of axonal damage and the severity of clinical signs suggested that the axonal damage may contribute to the clinical signs of the disease.
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PMID:Damage to bulbospinal serotonin-, tyrosine hydroxylase-, and TRH-containing axons occurs early in the development of experimental allergic encephalomyelitis in rats. 170 89

Electrophysiological studies were performed in Lewis rats with chronic relapsing experimental allergic encephalomyelitis (EAE) induced by inoculation with guinea-pig spinal cord and adjuvants and treatment with low dose cyclosporin A. During clinical episodes there was conduction failure in the central nervous system (CNS), namely the spinal cord dorsal columns, and in the afferent fibres in the peripheral nervous system (PNS). The following observations indicated that the conduction failure was mainly due to demyelination-induced conduction block: (1) rate-dependent conduction block in the CNS and PNS; (2) temporal dispersion due to slowing of PNS conduction; (3) restoration of PNS conduction by cooling; (4) restoration of CNS conduction by ouabain; (5) previously demonstrated histological evidence of primary demyelination in the dorsal columns, dorsal root ganglia and dorsal roots; and (6) the temporal association of restoration of conduction with remyelination. However, it is likely that CNS and PNS axonal degeneration, which occurs in this disease, also contributed to the conduction failure. In clinical remissions there was restoration of conduction in the CNS and PNS which can be explained by ensheathment/remyelination by oligodendrocytes and Schwann cells, respectively. In most rats during clinical episodes the cerebral somatosensory evoked potential was reduced in amplitude and prolonged in latency, which can be accounted for by demyelination and axonal degeneration in the CNS and PNS components of the afferent pathway. In 2 rats with episodes of EAE, however, this potential was markedly increased in amplitude, which might have been due to demyelination-induced conduction block of descending pathways that normally inhibit synaptic transmission in the afferent pathway. In well-established remission there was residual conduction failure in the CNS and PNS which can be mainly accounted for by axonal degeneration.
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PMID:The pathophysiology of chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. 188 81

The spectra of myelin sheath thickness and g ratio (axon diameter/fibre diameter) of guinea pig optic nerves for 8 animals with acute experimental allergic encephalomyelitis (EAE) were compared with those for 6 normal animals. The mean myelin sheath thickness of 0.12 microns for the animals with EAE was significantly lower than the value of 0.16 microns for the normal animals. Since fibre diameter comprises axon diameter plus the thickness of its surrounding myelin sheath, a reduction in mean fibre diameter from 1.52 microns in normals to 1.20 microns in EAE was expected, but it was surprising to find that a mean g ratio of 0.85 obtained for normal nerves was not substantially different from a value of 0.86 for demyelinated optic nerves. A decrease in the mean axon diameter of 1.24 microns for normal animals to 0.94 microns for those with EAE tended to offset the decrease in mean myelin sheath thickness and contributed to the relative stability of the g ratio with acute demyelination. Our results showing reduction in axonal calibre and myelin sheath thickness may offer an explanation for apparent discrepancies between electrophysiological delays in conduction characteristics of experimental and, if not the result of a maturational effect on myelination, human primary demyelinating disorders associated with the scant histopathological demyelination of initial attacks of EAE and the visually asymptomatic patients with multiple sclerosis.
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PMID:Maintenance of myelinated fibre g ratio in acute experimental allergic encephalomyelitis. 199 87

Neuropathological studies were performed in order to investigate experimental allergic encephalomyelitis induced by long-term cultured T cell lines and clones specific for myelin basic protein, which were established from SJL/J and DDD/1 mice. All antigen-activated T line or clone cells induced similar disease in euthymic and athymic mice with a common I-A haplotype. The lesion was characterized by perivascular and parenchymal infiltration of mononuclear cells with abundant polymorphonuclear cells located mainly in the lower spinal cord. Axons were severely affected and decreased in number. However, demyelination was present in all cases and was especially marked when recipient mice were: given whole-body X-ray irradiation, I-A compatible other strains, or were congenitally athymic. Topographically, demyelinated axons were most prominent in the root exit and entry zones of the lower spinal cord. Repeated transfer or relapse did not seem to be the factor responsible for enhancing demyelination. We conclude that: inflammation with axonal damage is the main feature of murine experimental allergic encephalomyelitis induced by myelin basic protein-specific T cell lines and clones, demyelination definitely occurs under certain conditions and in certain areas especially at the root exit and entry zones in nude mice, and a single T cell clone induces experimental allergic encephalomyelitis lesions associated with demyelination without the aid of interaction with another recipient-derived T cell population.
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PMID:Demyelination induced by T cell lines and clones specific for myelin basic protein in mice. 243 89

Bulbospinal monoamine-containing axons appear to be severely damaged in rats with the inflammatory and demyelinating disease, experimental allergic encephalomyelitis (EAE). This paper reports that although bulbospinal serotonin axons are damaged in the disease, cell bodies of origin in the medulla oblongata retain normal morphology. However, these serotonin cells are not able to retrogradely transport the enzyme horseradish peroxidase (HRP) from terminals in the lumbar spinal cord. Most non-serotonin-containing cells in the medulla which project to the lumbar spinal cord retain the ability to retrogradely transport HRP from the lumbar cord during the disease. These findings suggest that there is some specificity to spinal cord axonal damage during EAE.
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PMID:Retrograde transport of horseradish peroxidase is specifically impaired in bulbospinal serotonin axons during experimental allergic encephalomyelitis. 245 Jan 7

Immunohistochemical techniques were used to examine the morphology and distribution of monoamine- and substance P-containing fibers in the spinal cords of guinea pigs in acute paralytic, remission and relapse stages of chronic relapsing experimental allergic encephalomyelitis. During the initial paralytic attack, focal regions of axonal distortion appeared in the white matter of the cervical and thoracic cord; and axon terminal depletion in the gray matter of the caudal spinal cord was pronounced. This neuropathology persisted throughout remission and was exacerbated during relapse of paralysis. These results suggest that axonal damage is an important component of the pathophysiology of this autoimmune disease.
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PMID:Monoamine-containing fiber plexuses in the spinal cord of guinea pigs during paralysis, recovery and relapse stages of chronic relapsing experimental allergic encephalomyelitis. 246 19

Severe hypothermia and an ascending impairment of shivering are previously undescribed clinical signs in hyperacute experimental allergic encephalomyelitis (EAE) in the Lewis rat. These occurred in hyperacute EAE induced by inoculation with guinea pig spinal cord homogenate and heat-killed Bordetella pertussis. Hypothermia was first detected on day 6-7 post-inoculation, within 12-24 h of the onset of neurological signs, and became more severe as the disease progressed. Rectal temperatures less than or equal to 30 degrees C were common at ambient temperatures of 19-22 degrees C. Shivering was assessed by palpation and by cold tremor electromyography. Shivering was absent in the tail by day 6-7 post-inoculation. The impairment then progressed to affect the hindlimbs, thorax and occasionally the forelimbs. Shivering was absent in hindlimbs with only mild or moderate weakness. Histological studies revealed perivascular inflammation with polymorphonuclear and mononuclear cells, oedema, fibrin deposition, haemorrhage, primary demyelination and axonal degeneration in the spinal cord, dorsal root ganglia and spinal roots. The brainstem was also involved but the cerebral hemispheres, including the hypothalamus, were spared. The close relationship between the severity of hypothermia and the extent of shivering impairment indicates that reduced shivering is an important cause of hypothermia in hyperacute EAE. It is concluded that this impairment of shivering is due not to hypothalamic damage but to lesions elsewhere in the central and peripheral nervous systems.
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PMID:Hypothermia due to an ascending impairment of shivering in hyperacute experimental allergic encephalomyelitis in the Lewis rat. 261 69


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