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)

Spinal cord sections from Lewis rats with acute experimental allergic encephalomyelitis (EAE) showed greatly increased staining of astrocytes when stained immunocytochemically for glial fibrillary acidic protein (GFAP). Fibrous processes in white matter were heavily stained early in the course of the disease when paralysis was first evident (10-12 days after injection of guinea pig spinal cord myelin), then protoplasmic astrocytes were stained in the gray matter and became more heavily stained at 20 days post-injection. The stained astrocytes were evenly distributed throughout the tissue, and did not correspond to the sites of the lesions. Spinal cord slices of control and EAE rats were incubated with [3H]amino acids, then cytoskeletal proteins were prepared in an enriched fraction, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and the protein bands counted for radioactivity. In the EAE rat all cytoskeletal proteins, including the neurofilaments, vimentin, microtubules, GFAP and actin, showed increased uptake of radioactive amino acids. Immunoprecipitation of GFAP with specific antiserum showed increased radioactivity in the complex beginning at day 10 when cellular infiltration was beginning in the EAE animals. As the disease became acute, the radioactivity in the immunoprecipitated GFAP increased, in some cases to very high levels, then by day 18 when recovery was underway, the radioactivity had fallen to normal levels. Possible agents causing metabolic activation of protein synthesis in EAE animals include stimulating substances elaborated by infiltrating lymphoid cells, and the generalized edema accompanying the demyelinative condition. The activation of GFAP protein staining and metabolism in EAE might serve as a model for the activated growth of astrocyte processes which cause the severe gliosis seen in multiple sclerosis.
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PMID:Immunocytochemical staining for glial fibrillary acidic protein and the metabolism of cytoskeletal proteins in experimental allergic encephalomyelitis. 634 9

The immunological basis of multiple sclerosis (MS) is well recognized but the factors inducing MS lesions are unclear. In this study, we test the hypothesis that focal brain injury, inflicted during the pre-clinical stages of experimental allergic encephalomyelitis (EAE), will enhance the severity of immunological damage in the cerebral hemispheres and spinal cord. Acute EAE was induced in 30 Lewis rats by the injection of guinea pig spinal cord homogenate in complete Freund's adjuvant. A cryolesion to the surface of the left cerebral hemisphere was induced at 3 days (n = 6) or 8 days (n = 10) postinoculation (p.i.) and animals were killed at 15 days p.i. Control animals were EAE only (n = 9), cryolesion only (n = 4), EAE and sham cryolesion (n = 5) and normal animals (n = 3). Brain and spinal cord were stained by immunocytochemistry using W3/13 (T-lymphocytes) OX6 (MHC Class II) and GFAP (astrocytes) antibodies. The results showed a 2-fold increase in the number of EAE lesions in the brain with significant and widespread increase of MHC Class II antigen expression by microglia, in the cryolesion EAE 8 days p.i. when compared with EAE only animals. The pattern of enhancement suggests that it is due to (i) local spread of tissue or serum factors from the cryolesion; (ii) neural factors affecting remote regions of the CNS; (iii) stimulation of the immune system which may occur due to products of brain injury draining to regional cervical lymph nodes. Investigation of the mechanisms involved may prove fruitful in establishing factors which initiate, aggravate or ameliorate brain damage in multiple sclerosis.
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PMID:Focal brain damage enhances experimental allergic encephalomyelitis in brain and spinal cord. 747 27

To assess the distribution of insulin-like growth-factor-related proteins during autoimmune CNS demyelination and remyelination, experimental autoimmune encephalomyelitis was produced by injecting Lewis rats with an emulsion containing guinea pig spinal cord and complete Freund's adjuvant. Tail weakness appeared at 10-12 days and was followed by hind and forelimb weakness. Paraplegia and incontinence were observed in some animals. From 8-40 days postinoculation (dpi), spinal cord sections were used to correlate lesion location and severity with mRNA distributions of insulin-like growth factor I (IGF-I), IGF-binding protein 2 (IGFBP-2), IGF-I-receptor (IGFR-I), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP). These were determined semiquantitatively by in situ hybridization. Fourteen dpi, there were inflammatory infiltrates and demyelination in both white matter (WM) and grey matter (GM). IGF-I and GFAP mRNAs were increased in these lesions and transcripts encoding myelin basic protein (MBP) were greatly reduced. Large lesions with extensive demyelination were evident in both WM and GM when mRNA levels of GFAP and IGF-I peaked 26 dpi. MBP mRNA levels began increasing 21 dpi and peaked 26 dpi, when a few thin regenerating myelin sheaths were found morphologically. Astrocytes, identified by their morphology and GFAP immunoreactivity, expressed very low levels of IGFBP-2 mRNA and peptide in normal controls; their levels were significantly higher 14 dpi, peaked 26 dpi, and then gradually decreased. Some neurons, as well as oligodendroglia in areas undergoing remyelination, expressed IGFR-I. Although levels of IGF-I, IGFBP-2, and GFAP mRNAs were highest in lesion areas, levels were also elevated around lesions and in some normal-appearing areas of WM and GM 14-40 dpi. The gene expression of both IGF-I and IGFBP-2 by hypertrophic GFAP-positive astrocytes was demonstrated 14-40 dpi by combined in situ hybridization and immunocytochemistry as well as by double immunostaining. Coexpression of IGF-I and IGFBP-2 in the same astrocyte was a frequent finding. Relative increases in both IGF-I, GFAP, IGFBP-2, IGFR-I, and MBP mRNAs peaked at about the same time. This suggests that during lesion progression and recovery, astrocytic expression of IGF-I-related peptides may reduce immune-mediated myelin injury. We also suggest that astrocytic IGFBP-2 in lesions may help target IGF-I to IGFR-I-expressing oligodendrocytes and promote remyelination of demyelinated axons.
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PMID:Astrocytes express insulin-like growth factor-I (IGF-I) and its binding protein, IGFBP-2, during demyelination induced by experimental autoimmune encephalomyelitis. 752 31

Activation of astrocytes and hypertrophy of their processes is a result of a number of pathological conditions in the central nervous system. Astrocytic gliosis is especially prominent in multiple sclerosis (MS), where astrocytic fibers form a dense matrix around demyelinated axons. Experimental allergic encephalomyelitis (EAE), a laboratory model for MS, is also accompanied by astrocytic hyperactivity. We have previously shown the formation of plaque-like structures which stain heavily for glial fibrillary acidic protein (GFAP) in the brains and spinal cords of SJL/J mice after several episodes of chronic relapsing EAE (Smith and Eng: J Neurosci Res 18:203, 1987). To further investigate the mechanisms of this phenomenon, we have measured the levels of mRNA for GFAP throughout the course of three episodes and recoveries of EAE in the SJL/J mouse. Mice were immunized with spinal cord homogenate and subsequently developed EAE. After recovery they were again immunized at appropriate intervals, resulting in successive episodes of EAE, with partial or complete recovery between the paralytic stages. At appropriate times in the course of the different stages of EAE, spinal cords were dissected and RNA was prepared from each spinal cord. RNA was analyzed by Northern blots to determine the levels of mRNA for GFAP and, as a control for the 70 kDa neurofilament (NF-L). With the onset of the first EAE episode GFAP mRNA in spinal cords from animals with mild symptoms increased to sixfold the control level (P < 0.02) and to 20-fold in those with paralysis (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GFAP mRNA fluctuates in synchrony with chronic relapsing EAE symptoms in SJL/J mice. 759 Oct 33

The effects of increasing postmortem delay (PMD) times on morphological, immunological and functional characteristics of various brain cells both in situ and in vitro were studied in postmortem brain tissue derived from rats with acute experimental allergic encephalomyelitis (EAE). A decline of the brain tissue structure was first noted after a PMD of 6 h. Radial glia in the cerebellum were frequently interrupted and retractions artifacts appeared around brain cells. However, even after the longest PMD interval of 18 h the quality of the cell and tissue structure was still good enough for immunohistochemical characterization. Immunohistochemical staining of frozen and fixed rat brain tissue sections resulted in an enhancement of the immunoreactivity after a PMD of 4 h, using a panel of mono and polyclonal antibodies directed against glial fibrillary acidic protein (GFAP), basement membranes (laminin), brain macrophage antigens (ED1 and ED2), and various immunologically important surface molecules, such as major histocompatibility complex (MHC) class II (Ia) antigen (OX6), CR3 complement receptor (ED8), and leukocyte common antigen (OX1). No increase in staining intensities with the ED1, ED8 and OX6 mAbs specific for macrophage antigens could be detected on brain macrophages that were isolated from brain tissue of rats with EAE obtained after various PMD intervals. Irrespective of the PMD interval, viable astrocyte cell cultures were obtained with comparable staining intensities for GFAP. These cultured astrocytes were capable of ingesting Latex beads and were highly proliferative as measured by BrdU uptake, at all investigated PMDs. Thus, even after long PMD intervals, brain material can be used successfully. Other data suggest that the situation is similar to human brain material, even though the PMD times may be somewhat different.
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PMID:Postmortem delay effects on neuroglial cells and brain macrophages from Lewis rats with acute experimental allergic encephalomyelitis: an immunohistochemical and cytochemical study. 779 13

NF-kappa B is an inducible transcription factor involved in the induction of multiple genes during inflammatory processes. So far the information pertaining to the role of NF-kappa B in autoimmune processes has been restricted to in vitro analysis. To further characterize the role of NF-kappa B in vivo, the involvement of NF-kappa B has been studied by immunocytochemistry in T cell-mediated autoimmune encephalomyelitis (EAE) of the Lewis rat. In non-diseased animals, immunoreactivity for the DNA-binding subunit p50 and for the DNA-binding and transactivating subunit p65 was low and restricted to the surface of small to medium-sized blood vessels. Strong immunoreactivities for p50 and p65 were detected at the peak of clinical disease. At the recovery stage of EAE, p50 and p65 immunoreactivities had declined to base line levels. Within the resident glial cell population, p50 and p65-immunoreactive cells were identified as OX-42-positive microglia. GFAP-positive astrocytes did not show significant p50 or p65 immunoreactivity. In the core and the vicinity of perivascular inflammatory lesions, both ED-1-positive macrophages and W3/13-positive T lymphocytes and monocytes were strongly immunoreactive for NF-kappa B. Our data suggest a crucial involvement of the transcription factor NF-kappa B in autoimmune diseases of the central nervous system. Furthermore, NF-kappa B appears as a useful marker for inflammatory processes in vivo.
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PMID:Transcription factor NF-kappa B is activated in microglia during experimental autoimmune encephalomyelitis. 796 86

The expression of the 70-kDa heat shock cognate (HSC70) and stress-inducible (HSP70) proteins, and their mRNAs, was examined in experimental autoimmune encephalomyelitis, a model of inflammatory demyelination in the CNS. This study was undertaken as an extension of previous work demonstrating an abrupt decline in mRNA levels of both glial fibrillary acidic protein and the low-molecular-weight neurofilament subunit in experimental autoimmune encephalomyelitis spinal cord at 12 days after inoculation, the height of inflammation and clinical signs. Using the same total RNA preparations as our previous study, we report here that mRNA levels for HSC70 increased approximately sixfold over control values at the same time that glial fibrillary acidic protein and low-molecular-weight neurofilament subunit messages decreased and were similar to controls by 21 days after inoculation. In situ hybridization experiments showed that HSC70 mRNA was predominantly expressed in neurons and that the influx of inflammatory cells into the CNS was not responsible for the large increase in HSC70 message. Despite this elevation in mRNA, only small (if any) increases in protein levels for HSC70 were detected by both western blotting and in vitro cell-free translation systems. However, by quantitative immunoblotting, we determined that constitutive levels of HSC70 comprised a substantial portion of CNS proteins, representing 2-3% of the total protein content of spinal cord. Immunohistochemical staining illustrated that the distribution of HSC70 was consistent with that of its message. In contrast, no HSP70 mRNA or protein was detected in either control or experimental animals.
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PMID:The 70-kDa heat shock cognate protein (HSC70) is a major constituent of the central nervous system and is up-regulated only at the mRNA level in acute experimental autoimmune encephalomyelitis. 837 91

The potential for oligodendrocytes to proliferate in response to central nervous system injury was examined. We used intracerebral infection of Theiler's murine encephalomyelitis virus, a model for multiple sclerosis, which results in chronic demyelinating disease of SJL/J mice. Proliferating cells in spinal cord sections of adult mice were identified using simultaneous immunohistochemistry and in situ autoradiography ([3H]-thymidine incorporation). Seven different cell-specific markers were used to characterize proliferating cells as oligodendrocytes (myelin basic protein, proteolipid protein, galactocerebroside, CNPase), astrocytes (glial fibrillary acidic protein), microglia/macrophages (Griffonia simplicifolia isolectin B4) or T-lymphocytes (CD3). The average number of proliferating cells per area of spinal cord white matter was 11/mm2 in normal young adult mice compared to 61/mm2 in chronically infected mice. Most proliferating cells in normal spinal cord were not identified with these markers and were presumed to be progenitor glial cells. However, in spinal cord white matter of mice infected with Theiler's virus for approximately 4 months, 88% of proliferating cells were identified. Approximately one-third of all proliferating cells were in the oligodendrocyte lineage and expressed markers observed late in myelin differentiation. In demyelinated areas as compared to normal white matter, there was an 80- to 211-fold increase in the number of proliferating oligodendrocytes expressing myelin basic protein or proteolipid protein, respectively. The remainder of the proliferating cells in areas of demyelination were astrocytes, microglial cells and T-cells. These experiments support the hypothesis that factors within a demyelinating lesion promote the proliferation and differentiation of cells within the oligodendroglial lineage.
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PMID:The potential for oligodendrocyte proliferation during demyelinating disease. 838 Nov 62

By 24 h after mechanical trauma to the cerebral cortex, astroglial reaction begins and injury sites are infiltrated by activated mononuclear phagocytes derived from blood-borne monocytes and endogenous microglia. There is little information about cellular interactions between astrocytes and leukocytes during this process. We previously showed that murine astrocytes produce chemokines including monocyte chemoattractant protein-1 (MCP-1) during experimental autoimmune encephalomyelitis. In this study, we asked whether astrocytes produce MCP-1 in the absence of immune mediated inflammation. To address this question, we analyzed the time course and cellular source of MCP-1 in mouse brain after penetrating mechanical injury, with particular focus on early time points before histologic detection of infiltrating mononuclear phagocytes. We observed sharply increased steady state levels of MCP-1 mRNA within 3 h after nitrocellulose membrane stab or implant injury to the adult mouse brain, and MCP-1 protein elevations were documented at 12 h postinjury. In situ hybridization combined with immunohistochemistry for the glial fibrillary acidic protein astrocyte marker showed that astrocytes were the cellular source of MCP-1 mRNA at these early time points after mechanical brain injury. Stab injury to the neonatal brain evoked neither MCP-1 expression nor astrogliosis. These results demonstrate that chemokine gene expression comprises one component of the astrocyte activation program. The data are consistent with a role for MCP-1 in the central nervous system inflammatory response to trauma.
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PMID:Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain. 866 8

Reactive astrogliosis is a prominent pathological feature of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. It is characterized by hypertrophy of astrocytes with increased content of glial fibrillary acidic protein (GFAP.) Studies of reactive astrocytes in acute experimental autoimmune encephalomyelitis have been complicated by the observation that the diffuse increase in GFAP immunohistochemical staining at the onset of central nervous system inflammation does not parallel the gradual increase in GFAP content probably because tissue edema enhances GFAP immunostaining. To characterize changes in GFAP expression, we performed in situ hybridization at 3- to 7-day intervals during the course of acute murine experimental autoimmune encephalomyelitis. We found a biphasic course of GFAP expression: an early phase of astrocyte reaction surrounding perivascular inflammatory cuffs and submeningeal infiltrates at the onset of central nervous system inflammation and clinical disease and a later phase of increased GFAP mRNA expression in regions of demyelination during resolution of inflammation and clinical improvement. IP-10, a member of a family of proinflammatory chemoattractant cytokines called chemokines, was expressed by astrocytes in a similar distribution as those expressing increased GFAP mRNA in the early phase of inflammation but was no detected in astrocytes in the later phase of activation. These results indicate that location and function of reactive astrocytes may vary during the course of immune-mediated demyelination.
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PMID:In situ hybridization analysis of glial fibrillary acidic protein mRNA reveals evidence of biphasic astrocyte activation during acute experimental autoimmune encephalomyelitis. 877 43


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