Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conjugates of myelin encephalitogenic basic protein (EP) and commercial horseradish peroxidase (HRP) have been used for immunohistochemical demonstrations of anti-EP antibody in animals with experimental allergic encephalomyelitis. We performed gel electrophoresis studies on EP-HRP conjugates prepared with glutaraldehyde and on mixtures of EP and HRP incubated without glutaraldehyde. The results show that under conditions of one-and two-step coupling HRP causes rapid loss of the native EP band, apparently due to EP degradation. The EP-HRP mixtures are not encephalitogenic in rabbits, or encephalitogenic activity is lost during processing. The immunohistochemical reactivity of conjugates, however, signals some preservation of antibody-combining sites. The mechanism of the HRP effect on EP is unknown. The possibilities of a contaminating proteinase or direct peroxidatic attack are suggested. Until this action of HRP can be overcome, the effect of coupling procedures on the biological activities of EP will be difficult to assess, and EP-HRP conjugates cannot be expected to reveal sites that may bind encephalitogenic portions of the EP molecule.
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PMID:Commercial horseradish peroxidase degrades myelin encephalitogenic protein during coupling for immunohistochemical studies. 6 67

The blood-brain barrier (BBB) is recognized as a barrier to the trafficking of molecules and cellular elements into the central nervous system (CNS). Horseradish peroxidase (HRP) exclusion is used as a measure of BBB integrity. The BBB is altered and becomes permeable during the course of experimental allergic encephalomyelitis (EAE). Heterotopic brain transplantation into the anterior eye chamber is a technique for studying genetic influences and the role of individual cell types on the development of EAE. Prior to EAE induction, HRP is excluded from the central portion of the transplant, demonstrating an intact BBB. In contrast, HRP localization is found at the periphery of the transplant, suggesting an incomplete barrier. However, EAE lesions typically occur within the more central regions of the transplant, where the BBB is intact, and not at peripherally located "leaky" areas. This suggests that endothelial cells at intact BBB sites may direct trafficking of lymphocytes (gating) into the CNS during the development of EAE, rather than the passive entry of lymphocytes into the CNS through a leaky BBB.
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PMID:Distribution of the blood-brain barrier in heterotopic brain transplants and its relationship to the lesions of EAE. 137 10

Alterations in normal function of the blood-brain barrier (BBB) are important in the pathophysiology of multiple sclerosis and its laboratory counterpart, experimental autoimmune encephalomyelitis (EAE). As part of studies on drugs that affect vascular tone in rats with EAE, we have shown previously that the specific alpha 1-adrenoreceptor antagonist, prazosin, suppressed clinical and pathologic disease. In the present study we used quantitative morphometric analysis of capillary endothelium and the tracer horseradish peroxidase (HRP) to define effects of this drug on vascular events associated with central nervous system edema. In prazosin-treated and saline-treated EAE rats, protein extravasation in the spinal cord correlated with clinical presentation. Consistent with our previous data, the results showed that increased edema was associated with increased vesicular content of capillary endothelium. In prazosin-treated rats with no clinical signs, vesicular content was comparable to that found in normal animals. With increasing severity of disease, vesicular content increased and mitochondrial content decreased. In both prazosin- and saline-treated rats, mitochondrial content was reduced even when clinical signs were slight, and sharply declined when clinical signs increased. These results suggest that damage to mitochondria may be associated with early pathological events. In prazosin-treated animals, HRP accumulated in pericytes, suggesting that these cells were a target for the action of prazosin and may restrict the extravasation of fluid into the perivascular parenchyma. Our results underscore the presence of capillary changes associated with inflammation of the central nervous system, in addition to the well-recognized cellular inflammation that is targeted to the venular bed. The extent of capillary changes was closely associated with extent of tracer leakage in the spinal cord and support the conclusion that transcytotic vesicles are involved in transport of edema fluid during EAE, and that high mitochondrial levels are important for the normal function of BBB endothelium.
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PMID:Effects of prazosin on the blood-brain barrier during experimental autoimmune encephalomyelitis. 145 Sep 49

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease. It is widely used as an animal model of multiple sclerosis (MS). We studied the prophylactic effects of FK 506 electrophysiologically and immunohistochemically in acute EAE. Female Lewis rats were sensitized with guinea pig spinal cord in complete Freund's adjuvant. FK 506 suspended in distilled water was orally administered at 1.0, 3.2, 5.0 or 10.0 mg/kg per day for 12 successive days starting from the day of sensitization. A placebo was used as the control. Administration of FK 506 at doses of 3.2 mg/kg per day and over significantly delayed the onset of clinical signs. However, the FK 506 group showed a relapse or a chronic state following the onset of EAE. We made a time course recording of cortical somatosensory evoked potential (cortical SEP: P 15). P 15 latency in the placebo group was significantly delayed in accordance with the clinical signs and showed immediate improvement upon recovery. Prolongation of P 15 latency in the FK 506 group also occurred concomitantly with the clinical signs, but the delay continued after the loss of symptoms as well. After the onset of EAE, the infiltrating lymphocyte subset was examined by the avidin-biotin peroxidase complex (ABC) method in the lumbar spinal cord. In the placebo group, the number of OX3+ (Ia) cells and the W 3 25+: OX8+ (helper/inducer T: suppressor/cytotoxic T) ratio clearly reflected the development and remission of EAE. In the FK 506 group, however, increases in OX8+ lymphocytes were observed irrespective of clinical sign fluctuation, and there were corresponding decreases in the W 3/25+: OX8+ ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of novel immunosuppressant FK 506 in acute experimental allergic encephalomyelitis]. 169 82

Most of the central nervous system (CNS) endothelium regulates the passage of solutes and functions as a blood-brain barrier (BBB). During experimental autoimmune encephalomyelitis (EAE), an inflammatory demyelinating disease of the CNS, loss of BBB function occurs. The authors have previously shown an increase in endothelial transcytotic activity associated with decreased mitochondrial content as evidence of BBB dysfunction in EAE. These changes occurred in the capillary bed and correlated with CNS edema and clinical signs. In the present report, a fixation procedure before infusion of the intravascular tracer horseradish peroxidase (HRP) in rats at the height of clinical EAE has been used. In these animals, tracer leakage was only noted in inflamed venules with diameters of 12 to 19 mu. The authors detected several mechanisms of passive leakage: 1) increased junctional permeability; 2) increased interendothelial space; 3) leakage alongside migrating inflammatory cells. Some small capillaries showed necrotic changes with minimal tracer leakage. This report demonstrates that BBB disruption also occurs via nonendocytic mechanisms that may be induced by inflammatory cells.
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PMID:Mechanisms of edema formation in experimental autoimmune encephalomyelitis. The contribution of inflammatory cells. 224 Jan 57

The association of reactive oxygen species to altered permeability of the blood-brain barrier in acute experimental encephalomyelitis was investigated by ultrastructural cytochemical localization of hydrogen peroxide (H2O2) to sites in the optic nerve previously identified by extravasation of intravascular horseradish peroxidase. Using a modified cerium method, we found electron-dense cerium-derived H2O2 reaction product was localized to the perivascular space at the lamina retinalis, lamina choroidalis, and lamina scleralis. In the optic nerve head, electron-dense reaction product was observed in the presence of intravascular leukocytes, although adjacent perivascular and interstitial inflammatory cells at this site were scant. In the myelinated retrobulbar optic nerve, cerium-derived H2O2 reaction product was seen in the intravascular space of blood vessels and surrounding perivascular and interstitial foci of inflammatory cells. Reaction product was also observed in the extracellular space adjacent to the plasmalemma of axons and glial cells in the optic nerve head and retrobulbar nerve. The perivascular and intravascular distribution of cerium-derived reaction product suggests that H2O2 may play a role in the pathogenesis of altered vascular permeability in experimental optic neuritis and supports our previous observations of suppression of blood-brain barrier permeability by detoxification of H2O2 with the exogenous administration of antioxidant enzymes.
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PMID:Hydrogen peroxide localization in experimental optic neuritis. 224 46

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

Chronic relapsing experimental allergic encephalomyelitis (EAE) lesions that resemble those seen in multiple sclerosis (MS) were produced in young Hartley and strain 13 guinea pigs (Lassmann and Wisniewski 1979). To study distributions of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP) in these lesions, paraffin and semithin epon sections of CNS from eight of these guinea pigs were immuno-stained with antisera to these proteins according to the peroxidase-antiperoxidase (PAP) method. In lesions with active myelin sheath breakdown, changes in anti-MAG and anti-BP immunoreactivity corresponded closely. Abnormal and/or decreased anti-MAG staining did not extend beyond margins of lesions into surrounding areas containing myelin sheaths stained normally by anti-BP and by histological stains for myelin. GFAP-stained astrocyte processes were more numerous and much larger in more chronic lesions. Anti-MAG and anti-BP both stained regenerating myelin sheaths which were very numerous in both paraffin and epon sections. In the latter, anti-MAG also stained some myelin-forming oligodendroglia. The results are additional evidence suggesting that in chronic relapsing EAE, myelin sheaths are the primary target. Oligodendroglia appear to be relatively unaffected and remyelinate most of the demyelinated axons.
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PMID:Immunocytochemical study of myelin-associated glycoprotein (MAG), basic protein (BP), and glial fibrillary acidic protein (GFAP) in chronic relapsing experimental allergic encephalomyelitis (EAE). 257 17

Mechanisms involved in the loss of blood-brain barrier function in Lewis rats with experimental autoimmune encephalomyelitis (EAE) were examined using horseradish peroxidase (HRP) as a tracer. In animals injected with HRP before fixation, tracer was observed in two intracytoplasmic compartments: multivesicular bodies (presumably secondary lysosomes) and transcytotic vesicles. Quantitative morphometry of electron micrographs of capillary endothelial cells demonstrated a 5.2-fold increase in these vesicles. This increase in vesicular transport was associated with a decrease in mitochondrial content from 13.7% of the endothelial cytoplasmic area in the normal rat to 4.2% in EAE rats at the height of clinical disease. These alterations correlated with the clinical course of EAE. In animals infused with tracer after fixation, tracer was restricted to areas of cellular inflammation. Immunogold staining of endogenous albumin demonstrated the presence of albumin in cytoplasmic vesicles and in channel-like tubular structures adjacent to endothelial cell junctions. These results indicate that there is a role for vesicles in transendothelial cell transport and edema formation in animals with EAE.
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PMID:Increased vesicular transport and decreased mitochondrial content in blood-brain barrier endothelial cells during experimental autoimmune encephalomyelitis. 259 75

We induced chronic relapsing experimental allergic encephalomyelitis (EAE), and studied the ultrastructural and ultracytochemical changes of the blood-brain barrier (BBB) in the demyelinating lesions of various stages of EAE. In the chronic, inactive stage with gliosis and perivascular fibrosis, the basal lamina (BL) of the perivascular processes of astrocytes was formed only partially, and neural parenchyma was not fully separated from the perivascular mesenchymal tissues by the BL of astrocytic processes. Vascular permeability of the BBB was studied using exogenous horseradish peroxidase (HRP) as the tracer: HRP extravasation was marked during the stages of both active myelin breakdown and removal of debris, and was recognized even at the inactive stage, although the degree was reduced to a very low level. The functions of the endothelia, assessed by ouabain-sensitive, K+-dependent p-nitrophenylphosphatase activity, were impaired as EAE progressed. The decrease in HRP leakage at the inactive stage suggests the endothelial impairment of active transport of metabolites including HRP. Along with the development of inflammatory demyelination in EAE, the BBB in affected areas became more and more altered, and gradual morphological and functional impairment of the BBB developed.
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PMID:Ultrastructural and ultracytochemical studies on the blood-brain barrier in chronic relapsing experimental allergic encephalomyelitis. 271 44


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