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Bibliographies thématiques / Experimental Autoimmune Encephalomyelitis, Progesterone / Thèses

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Thèses sur le sujet « Experimental Autoimmune Encephalomyelitis, Progesterone »

Auteur : Grafiati

Publié le 9 mars 2023

Mis à jour le 10 mars 2023

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1

BALLARINI, ELISA. « Caratterizzazione di un modello di encefalomielite autoimmune sperimentale e ruolo neuroprotettivo del progesterone ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2012. http://hdl.handle.net/10281/39833.

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Studies concerning the role of neuroactive steroids in chronic models of Experimental Autoimmune Encephalomyelitis (EAE) are still scarce. First we considered different pathological targets in Dark Agouti (DA) rats affected by EAE in order to well characterize this chronic model of Multiple Sclerosis (MS) which well reflects the relapsing-remitting form of MS. We analyzed neuroinflammatory profile, assonopathy and neuroactive steroid levels in the spinal cord of DA rats affected by EAE. Data obtained at 14 dpi (i.e. days post induction) showed that acute neurological signs were associated with infiltrating T cells (CD3+) and macrophages (ED1+) and with microglial activation (MHC-II+ cells) which were accompanied by an increased expression of pro- and anti-inflammatory cytokines in the spinal cord. We immunolocalized a few damaged axons (SMI-32+) in the spinal cord white matter, moreover we identified a general decrease in the level of most neuroactive steroids analyzed. At 45 dpi we observed a decrease of inflammatory infiltration, of microglial cell activation and of cytokine gene expression respect to EAE rats at 14dpi. Assonopathy was exacerbated as demonstrated by the increase in SMI-32 immunoreactivity and by the decreased Na+,K+-ATPase activity. Changes in the neuroactive steroid level observed at 14dpi were maintained or reverted at 45dpi. Interestingly, the level of progesterone (PROG) significantly decreased only at 45dpi suggesting a possible role of this neuroactive steroid in the chronicization of EAE. Basing on this evidence, we performed a second study aimed to evaluate the possible neuroprotective properties of PROG treatment in DA rats affected by EAE. Data obtained at 45 dpi showed that PROG was able to improve EAE course by reducing the spinal cord neuroinflammation and microglia activation. Moreover PROG treatment was able to promote a functional recover of axons and to counteract the MBP protein reduction observed in EAE rats. Finally an increase in the levels of dihydroprogesterone and isopregnanolone (i.e. two PROG metabolites) was also observed in the spinal cord after PROG treatment providing evidence on PROG metabolic profile. Taken together these results indicate that PROG may have a role in the pathogenesis of EAE and that it is effective in reducing the severity of EAE in DA rats. Consequently our data may represent an interesting background for future treatments of MS based on synthetic analogous of PROG.

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2

Harness, Jacqueline. « Immunoregulation of experimental autoimmune encephalomyelitis / ». St. Lucia, Qld, 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17375.pdf.

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3

Isaksson, Magnus. « Initiation of Autoimmunity in Experimental Autoimmune Encephalomyelitis ». Doctoral thesis, Uppsala universitet, Molekylär medicin, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-173427.

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The events that trigger an autoimmune disease remain largely unknown. To study these events animal models are necessary because symptoms of autoimmune diseases are preceded by a long asymptomatic period in humans. Experimental autoimmune encephalomyelitis (EAE) is the best characterized model for cell mediated autoimmunity and an animal model for the human disease multiple sclerosis. EAE is induced in rodents by immunization with myelin antigens (Ags) together with adjuvants. After immunization, T cells are primed in the periphery by Ag presenting cells and subsequently invade the central nervous system where they mediate parenchymal inflammation, resulting in demyelination and clinical symptoms of an ascending paralysis. It is now generally recognised that the main cell type mediating EAE is the T helper type 17 (Th17) cell. Tolerance to EAE can be attained by DNA vaccination, but how the immune response against the myelin Ags is abrogated after DNA vaccination is not known. By employing short interfering RNA technology, induction of the innate immune signalling molecule interferon (IFN) -β was found to be necessary for the protective effect of DNA vaccination in EAE. In addition, DNA vaccination inhibited subsequent autoimmune Th17 cell responses. The Toll-like receptors (TLRs) of the innate immune system have evolved to recognise conserved molecular structures on microbes and signalling through them almost exclusively converge on the molecule MyD88. Signalling via MyD88 was found to be required for induction of EAE since mice deficient in this molecule did not develop disease. Upstream signalling via TLR4 and TLR9 had tolerogenic properties. In studies of Ag presentation in EAE, two major subtypes of dendritic cells (DCs) were examined. Plasmacytoid DCs were found to have a promoting role in the induction of EAE, partly via type 1 IFNs. Myeloid DCs had a redundant role in the induction phase of EAE, neither disease severity nor encephalitogenic Th17 responses were affected by their absence during priming. These studies further demonstrate that the cells and molecules of the innate immune system exhibit a crucial role in controlling the adaptive immune system which mediates tissue damage in autoimmune diseases.

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4

Ruppova, Klara. « Role of eosinophils in experimental autoimmune encephalomyelitis ». Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-231835.

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Experimental autoimmune encephalomyelitis (EAE) is the rodent model of multiple sclerosis (MS), a chronic autoimmune neuroinflammatory disease that has a devastating impact on various neurological functions of the patients. The hallmarks of both, MS and EAE, are neuroinflammation, demyelination and neuroaxonal degeneration. Various types of lymphoid and myeloid cells were shown to infiltrate the central nervous system and to participate in disease pathology. However, the role of eosinophil granulocytes has been less explored thus far. An early study showed that eosinophils infiltrate into the spinal cord of EAE mice and suggested their role in the disease progression. Recently, it was reported that eosinophils can play a protective role against EAE when mice are treated with an extract from helminths. Furthermore, it was shown that EAE development is not altered in mice deficient for interleukin-5, an important eosinophil pro-survival factor. Taken together, the role of eosinophils in EAE is currently unclear and needs to be investigated in detail. In the present study, we use the active model of EAE, whereby we immunized the C57BL/6 mouse strain with MOG35-55 peptide emulsified in the complete Freund’s adjuvant, in order to study a possible contribution of eosinophils to the disease pathology. Using the flow cytometry and RT-qPCR analysis of the spinal cord, we show that eosinophils infiltrate into the tissue in the course of EAE. The infiltration is likely driven by eosinophil chemoattractants, such as eotaxin-1, as the concentration of the latter was increased in the spinal cord during EAE, as shown on mRNA and protein level. Moreover, detailed flow cytometry analysis of spinal cord eosinophils revealed that they show signs of activation, namely an increase in CD11b and decrease in CCR-3 surface expression. Furthermore, we observed signs of degranulation of spinal cord eosinophils in EAE which was measured as a decrease of the side scatter parameter and an upregulation of CD63 surface expression. These data suggest a potential role of eosinophils in the pathology of EAE. In order to elucidate whether eosinophils are important for the disease development, eosinophil-deficient mice were subjected to EAE and the clinical development of the disease was observed. For this purpose, we used two independent models of eosinophil deficiency - ΔdblGATA1 and interleukin-5-depleted mice. ΔdblGATA1 mice are a genetically manipulated mouse strain bearing a deletion in GATA1 promoter that causes a specific depletion of eosinophils. Interestingly, clinical development of EAE was not affected in these mice when compared to their wild-type controls. As a next step, we depleted eosinophils by injecting wild-type mice with an antibody against the eosinophil pro-survival factor interleukin-5 in order to reduce eosinophil numbers in the effector phase of EAE. In accordance with the result from the experiment with ΔdblGATA1 mice, EAE progression was not altered in the eosinophil-depleted mice when compared to mice that were injected with an isotype control antibody. Further, we analyzed the neuroinflammation and demyelination in the spinal cord of 4ΔdblGATA1 mice subjected to EAE. Specifically, the infiltration of inflammatory cell populations, including CD4 and CD8 T cells, neutrophils and macrophages, was assessed by flow cytometry. In agreement with the unchanged clinical EAE development, inflammatory cell infiltration was not affected in ΔdblGATA1 mice. Furthermore, we analyzed expression of pro-inflammatory cytokines in the spinal cord of ΔdblGATA1 mice subjected to EAE in order to better characterize the inflammatory status. No significant changes were detected further confirming that eosinophils do not contribute to neuroinflammation in EAE. Finally, we assessed the demyelination in the spinal cord of ΔdblGATA1 EAE mice using luxol fast blue staining to detect myelin. In accordance with the unaffected clinical development and inflammatory status, we did not observe any difference in the spinal cord demyelination in ΔdblGATA1 mice when compared to their wild-type littermates. Taken together, although eosinophils infiltrate into the spinal cord of EAE mice and are activated and degranulate therein, they are dispensable for EAE development.

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Weissert, Robert. « Immunogenetics and treatment of experimental autoimmune encephalomyelitis / ». Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3645-5/.

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Lobell, Anna. « Suppressive DNA vaccination in experimental autoimmune encephalomyelitis / ». Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3782-6/.

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7

Dowdell, Kennichi C. « Neuroendocrine regulation of relapsing Experimental Autoimmune Encephalomyelitis / ». The Ohio State University, 1999. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488191124569455.

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8

Wefer, Judit. « Studies of cellular pathogenesis in experimental autoimmune encephalomyelitis / ». Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-023-0/.

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Wållberg, Maja. « Modulation of immune responses in experimental autoimmune encephalomyelitis / ». Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-335-3/.

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10

Berl, Sabina [Verfasser]. « Neuronal Response to Experimental Autoimmune Encephalomyelitis / Sabina Berl ». Mainz : Universitätsbibliothek Mainz, 2020. http://d-nb.info/1203322933/34.

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11

Koutrolos, Michail. « Role of regulatory T cells in experimental autoimmune encephalomyelitis ». Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-161896.

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12

Tran, Elise H. « Immune invasion and glial activation in experimental autoimmune encephalomyelitis ». Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36845.

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Leukocyte recruitment into tissues in response to infection or injury is a crucial event for the elimination of pathogens to protect the host. However, when leukocytes invade the central nervous system (CNS) and neuromflammatory disorders result, neurological function may be compromised. Infiltration of the CNS, predominantly by T cells and macrophages, characterizes Multiple Sclerosis and its animal counterpart, Experimental Autoimmune Encephalomyelitis (EAE).
Autoreactive T cells that initiate EAE produce Th1 cytokines (e.g., IFNgamma, TNFalpha). Nevertheless, previous studies also indicated an unnecessary or even protective role for IFNgamma in EAE. I have identified a novel role for IFNgamma in my studies using IFNgamma- or IFNgammaR-knockout mice. IFNgamma promotes the expression of the chemokines RANTES, MIP-1alpha, and MCP-1, which recruit mononuclear cells in the CNS to induce a non-lethal remitting EAE. Without IFNgamma, the chemokines MIP-2 and TCA-3, and polymorphonuclear leukocytes prevail, producing an unusually lethal EAE. MIP-1alpha is, however, dispensable in recruiting mononuclear cells, as EAE could still be induced in mice deficient in MIP-1alpha or its CCRS receptor.
To examine how much T cells depend on the cooperation with macrophages in the CNS to induce EAE, selective depletion of peripheral macrophages in mice was achieved by intravenous administration of clodronate-loaded liposomes. Treated mice showed no clinical signs of EAE following adoptive transfer of myelin-reactive T cells, but an altered distribution of leukocytes. These leukocytes were confined within the perivascular or meningeal space, not invading the CNS parenchyma. Levels of TNFalpha and inducible nitric oxide synthase (iNOS) in the CNS were reduced in these asymptomatic macrophage-depleted mice compared to untreated mice with EAE. In these asymptomatic mice, NOS expression was restricted to parenchymal astrocytes. In mice with EAE, however, both macrophages/microglia and astrocytes in infiltrates expressed NOS. Surprisingly, some astrocytes that were distant from infiltrates also expressed NOS, thus suggesting that astrocytes may modulate leukocyte infiltration via release of NO through their foot processes in the blood-brain barrier. Collectively, my data propose a model of a dynamic network in which the interplay among cytokines, chemokines and nitric oxide, may determine the magnitude, the composition, or the resolution of inflammatory infiltrates, as well as the clinical outcome of EAE.

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13

Fuller, Kathleen Ann. « Oral tolerance in experimental autoimmune encephalomyelitis : the humoral arm / ». The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu148767684711592.

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14

Jagodić, Maja. « The complex genetics of experimental autoimmune neuroinflammation / ». Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-157-1/.

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DE, CEGLIA ROBERTA. « Unraveling the role of cns acidosis in experimental autoimmune encephalomyelitis ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2013. http://hdl.handle.net/10281/46925.

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Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the Central Nervous System (CNS) featuring severe neuronal degenerative processes. Emerging findings indicate that several injurious molecular and cellular cascades are contributing to neurodegeneration. Among them, CNS acidosis has been recently demonstrated to have a detrimental role in Experimental Autoimmune Encephalomyelitis (EAE). Good candidates to trigger acidosis-mediated neurodegeneration are represented by Acid Sensing Ion Channels (ASICs) which are H+-gated cation channels of the CNS. We measured CNS acidosis in EAE mice by a non-invasive magnetic resonance spectroscopy (MRS), establishing the presence of a substantial extracellular acidification in the Cerebellum (CB). We next examined the ability of Diminazene Aceturate (DA), a new specific ASICs inhibitor, to promote neuroprotective effects in chronic EAE mice. Behavioral and histological evaluations indicated that DA significantly improved walking performances in EAE mice, ameliorated their neurological deficits, as well as, reduced myelin and axonal loss in both CB and Spinal Cord. Additionally, we model in vitro the harmful electrophysiological alterations elicited by acidosis using primary neuronal cultures coupled with Micro Electrode Array (MEA) devices. While an acute acidic treatment caused a rapid and transient reduction of firing activity, long term acidosis caused the chronic impairment of synchronized neuronal electrophysiological activity, and a significant loss of pre-synaptic boutons. DA efficiently compensated the loss of firing activity derived from acute acidosis, as well as protected neurons from injurious effects elicited by chronic acidosis. In conclusion our data suggest that ASICs activation is involved in mediating neuronal derangement during acute neuroinflammation and that the early intervention with specific ASICs antagonists may attenuate these detrimental effects.

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Eltayeb, Sana. « Chemokine receptor expression and function in experimental autoimmune neuroimflammation / ». Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-197-5/.

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Papenfuss, Tracey L. « Hormones and dendritic cells influences on the initiation of the autoimmune disease experimental autoimmune encephalomyelitis / ». Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1173196704.

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Duan, Rui-Sheng. « Inflammation and neurodegeneration in mouse nervous system : experimental application / ». Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-606-9/.

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Kalyvas, Athena. « The role of the phospholipase A₂ family in experimental autoimmune encephalomyelitis / ». Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111895.

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Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that is characterized by widespread focal areas of inflammation and demyelination. Although the exact cause of the disease is still not known, myelin-reactive T cells that enter the CNS trigger the disease and lead to the recruitment and activation of macrophages and other immune cells. One set of candidates that could serve to mediate these CNS changes is the family of phospholipase A2 (PLA2) enzymes, which consist of secreted (sPLA2) and cytosolic (cPLA2) forms. These enzymes hydrolyze membrane phospholipids to release free fatty acids (arachidonic acid) that can stimulate complex inflammatory cascades, and lysophospholipids that can induce myelin breakdown and demyelination, the two pathological hallmarks of MS.
For my Ph.D. research I studied the expression and role of different members of the PLA2 family in 'experimental autoimmune encephalomyelitis' (EAE), a widely used animal model of MS. I first generated a relapsing-remitting form of EAE in the C57BL/6 mouse strain that lacks a major form of sPLA2. I showed that cPLA2 is expressed by immune cells in the EAE lesions in the CNS. Furthermore blocking the activity of cPLA2 with a broad-spectrum chemical inhibitor starting at the time of EAE induction reduced the incidence and severity of disease, reduced lesion burden as well as reduced the expression of a number of chemokines and cytokines. Treating mice in the remission phase also prevented further clinical episodes. This showed that some or all members of the cPLA2 family play an important role in the onset and progression of EAE in a strain of mice lacking sPLA2.
I next carried out studies to assess the expression of all 14 members of the sPLA2 and cPLA2 families at the onset, peak and remission stages of EAE in the SJL/J mouse strain that expresses all forms of PLA2. The mRNA expression of only 4 of these PLA2s was increased. These include sPLA2 (groups IIA and V) and cPLA 2 (groups IVA and VIA). The expression of these PLA2s in the CNS was also characterized by double-immunofluorescence. The role of these PLA2s was assessed using selective inhibitors and analysed by monitoring the clinical disability scores, chemokine/cytokine protein arrays, lipomics lipid profiling, and histological analysis. Surprisingly, the sPLA2 inhibitor prevented disease remission and worsened the clinical outcome. This was accompanied by an increase in several pro-inflammatory chemokines. Selective inhibitors of cPLA2 group IVA and the calcium independent foam group VIA (iPLA2) reduced severity of EAE when given starting before onset of disease. The cPLA2 inhibitor treatment was effective only while administered, while iPLA2 inhibitor treatment was effective even after treatment was stopped. Furthermore, only delayed treatment with the iPLA2 inhibitor was effective, suggesting that cPLA2 group IVA only plays a role in the initiation of disease, while iPLA 2 plays a role in both disease onset and progression. These effects were also associated with concomitant reduction in chemokine/cytokine expression, reduction of inflammatory lipid mediators, and increase in protective lipids e.g., omega 3 fatty acids.
This work has allowed us to dissect out the expression and role of different members of the PLA2 family and has revealed the importance of selectively inhibiting some but not others in EAE. These findings may therefore have important implications for the treatment of MS.

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Anwar, Mohammad Ashraful. « SPARC modulates the spinal cord neuroimmune response in experimental autoimmune encephalomyelitis ». Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/46047.

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SPARC (Secreted Protein Acidic and Rich in Cysteine), a secreted glycoprotein, regulates proliferation, migration and differentiation. SPARC is highly expressed in glia and blood vessels during CNS development. SPARC expression is maintained in tissues undergoing rapid turnover and its expression is highly upregulated during injury or disease. SPARC’s modulatory activity in glia and endothelia during injury lead us to investigate the role of SPARC in an animal model of CNS inflammation and demyelination with known BBB dysfunction: Experimental Autoimmune Encephalomyelitis (EAE). We discovered that, in the spinal cord, SPARC is expressed and localized to developing endothelia and radial glia but is down-regulated and retained in specific subpopulations of glia in the adult spinal cord. During the repair response of EAE, CNS glia and endothelia recapitulate their developmental SPARC expression. Furthermore, in the absence of SPARC, EAE onset is delayed even though there is increased blood-brain barrier (BBB) permeability. We provide evidence that SPARC may play a role in neuro-immune and endothelial cross-talk during the repair response following EAE.

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Srinivasan, Mythily. « Costimulatory blockade by CD28 Peptide mimics : suppression of experimental Autoimmune Encephalomyelitis / ». The Ohio State University, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488205318509738.

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Esaki, Yoshiyasu. « Dual roles of PGE2-EP4 signaling in mouse experimental autoimmune encephalomyelitis ». Kyoto University, 2011. http://hdl.handle.net/2433/142551.

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PETROSINO, VALENTINA. « MOLECULAR MECHANISMS UNDELYING REST DYSREGULATION IN THE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE) ». Doctoral thesis, Università degli studi di Genova, 2019. http://hdl.handle.net/11567/945765.

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The development and maturation of the nervous system imply a precise temporal and spatial modulation of gene expression, coordinated by transcriptional enhancers and repressors. In this context, the key role of repressor element 1-silencing transcription factor (REST) is largely known. REST regulates neurogenesis and neuronal identity through cell-specific gene repression, allowing expression of its targets in mature neurons. During neuronal development REST levels are reduced and REST is quiescent in mature neurons, which are able to modulate its expression in response to pathological stimuli. Such dysregulation has been implicated in several neurodegenerative disorders, including Alzheimer’s and Huntington’s diseases, tumors of the central nervous system (CNS) and epilepsy. Our pilot study had indicated that REST is significantly over-expressed in murine chronic experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS), at acute early phase. MS is a CNS autoimmune-mediated disease characterized by chronic inflammation and demyelination in the white and grey matter leading to an impairment of synaptic transmission and network connectivity, with both neuronal and axonal loss. Chronic inflammatory processes that continuously disturb neuro-axonal homeostasis drive neurodegeneration, so the clinical outcome is likely to depend on the balance between inflammation and the remaining capacity for neuronal self-protection and repair. Hence, therapeutic approaches halting neurodegeneration and promoting tissue repair are sorely needed. On this matter, specific targeting of REST-dependent transcription and/or molecular pathways could be an appealing strategy towards therapy in MS. In this project, we have addressed REST expression throughout disease to characterize the role of its unbalance in EAE, assess its potential as biomarker for disease progression, and understand if modulation of REST leads to rescue of EAE phenotype. Starting from these observations, we have first analyzed the expression of REST and its target genes in vivo, during EAE, and in vitro, in the context of neuroinflammation investigating the differential contribution of REST transcripts to REST up-regulation and how this affects its targets. Moreover, in order to study the cellular and molecular pathways involved in the processes of neuroinflammation, we have analyzed REST activity in cell culture, under inflammatory conditions mimicking the EAE microenvironment. Our results support the involvement of REST in the pathological process of EAE, suggesting a possible mechanism of action of REST in the control of its target gene expression in response to neuroinflammation, and demonstrating the involvement of signal pathways regulating REST expression, under these conditions.

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Axtell, Robert C. « The role of CD5 in experimental autoimmune encephalitomyelitis ». Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. http://www.mhsl.uab.edu/dt/2007p/axtell.pdf.

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de, Graaf Katrien L. « Molecular basis for the MHC class II association in rat experimental autoimmune encephalomyelitis / ». Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4857-7/.

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Short, Abigail E. « The role of MIF production by B lymphocytes in experimental autoimmune encephalomyelitis ». Connect to resource, 2010. http://hdl.handle.net/1811/45462.

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Esposito, Marianna. « Immune Regulation in Experimental Autoimmune Encephalomyelitis : the Role of Regulatory T cells ». Thesis, Open University, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.503627.

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Agnello, Davide. « Erythropoietin crosses the blood-brain barrier and protects against experimental autoimmune encephalomyelitis ». Dijon, 2003. http://www.theses.fr/2003DIJOMU05.

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L'érythropoi͏̈étine (EPO), administrée par voie systémique, traverse la barrière hématoméningée et a chez l'animal des effets protecteurs sur l'ischémie cérébrale, le traumatisme cérébral et protège également de l'encéphalomyélite autoimmune expérimentale chez le rat. Dans un second travail, nous avons caractérisé l'effet de l'administration systémique d'EPO sur la composante inflammatoire induite lors de l'encéphalopathie autoimmune expérimentale aigue͏̈ chez le rat Lewis. L'administration quotidienne d'EPO aux doses de 500-500 U/kg en intrapéritonéal à partir du 3e jour après l'immunisation avec une protéine de myéline (myelin basic protein) retarde le début de l'encéphalopathie et diminue la symptomatologie notamment lorsque celle-ci est à son maximum (J12-J13). L'analyse immunochimique de la moelle épinière à l'aide d'anticorps monoclonaux anti-"glial fibrillary acidic protein" (GFAP) montrait que l'EPO diminuait significativement l'inflammation et l'activation/prolifération des cellules gliales. L'encéphalomyélite autoimmune expérimentale induit une augmentation des taux de TNF et d'IL-6 dans le LCR, où l'IL-6 atteint son maximum au début de la maladie (J10) et le TNF à J12. L'EPO retarde l'augmentation du TNF sans modifier le pic, et réduit significativement les taux d'IL-6. Ces résultats suggèrent que la diminution de l'inflammation et de la symptomatologie peut-être liée à la diminution des taux d'IL-6. D'autre part, l'EPO est sans effet dans un modèle d'arthrite induite par un adjuvant chez le rat Lewis, suggérant que l'EPO pourrait agir comme une cytokine protégeant le système nerveux central des pathologies inflammatoires.

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Azzam, Sausan. « Protein Profiling Analysis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis Brain Tissue ». Kent State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=kent1302472724.

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Yang, Jinghui. « Peripheral immune response in chronic relapsing experimental autoimmune encephalomyelitis in SJL mice ». Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/laa/haart/vk/yang/.

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WOLDETSADIK, ABIY DEMEKE. « Development of nanoparticle platforms for “inverse vaccination” in experimental autoimmune encephalomyelitis (EAE) ». Doctoral thesis, Università del Piemonte Orientale, 2014. http://hdl.handle.net/11579/46149.

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Dahlman, Ingrid. « Genetic dissection of experimental autoimmune neuroinflammatory diseases in rats / ». Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3768-0/.

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Xu, Ling-Yun. « Mechanisms and modulation of experimental allergic encephalomyelitis as basis for treatment of multiple sclerosis / ». Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4452-0/.

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Lassmann, Silke. « Antigen-dependent regulation of cytokine and chemokine expression in EAE ». Thesis, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287992.

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Vuong, Linda. « Toll-like receptor 7 tolerance in anti-neuroinflammation in murine experimental autoimmune encephalomyelitis ». Diss., [La Jolla] : University of California, San Diego, 2010. http://wwwlib.umi.com/cr/fullcit?p1477944.

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Thesis (M.S.)--University of California, San Diego, 2010.
Title from first page of PDF file (viewed July 12, 2010). Available via ProQuest Digital Dissertations. Includes bibliographical references (leaves 50-64).

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Jabs, Claudia. « Roles of the B7-CD28 superfamily in the regulation of experimental autoimmune encephalomyelitis ». [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=964802090.

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Abdul-Majid, Khairul-Bariah. « Pathogenesis of myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis in DBA/1 mice / ». Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-112-8/.

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Floßdorf, Juliane [Verfasser]. « The role of PPARγ in myeloid cells in experimental autoimmune encephalomyelitis / Juliane Floßdorf ». Bonn : Universitäts- und Landesbibliothek Bonn, 2013. http://d-nb.info/1044970332/34.

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Meyer, Abbie L. « Oral tolerance to myelin basic protein in mice : suppression of experimental autoimmune encephalomyelitis / ». The Ohio State University, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487934589975749.

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Wohler, Jillian E. « The role of the [beta]₂-integrin family on T cell subsets ». Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2009. https://www.mhsl.uab.edu/dt/2009p/wohler.pdf.

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Steinbach, Karin [Verfasser], et Roland [Akademischer Betreuer] Martin. « Role of autoimmune inflammation and impaired neurodegeneration in the pathogenesis of experimental autoimmune encephalomyelitis / Karin Steinbach. Betreuer : Roland Martin ». Hamburg : Staats- und Universitätsbibliothek Hamburg, 2011. http://d-nb.info/1020384395/34.

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McClain, Melanie A. « Pregnancy and the post-partum period regulate experimental autoimmune encephalomyelitis through immunoregulatory cytokine production ». Connect to this title online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1119898792.

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Thesis (Ph. D.)--Ohio State University, 2005.
Title from first page of PDF file. Document formatted into pages; contains xv, 95 p.; also includes graphics (some col.) Includes bibliographical references (p. 85-95). Available online via OhioLINK's ETD Center

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Schubart, Anna. « Aspects of the Immunobiology of Myelin Oligodendrocyte Glycoprotein (MOG)-induced Experimental Autoimmune Encephalomyelitis (EAE) ». Diss., lmu, 2002. http://nbn-resolving.de/urn:nbn:de:bvb:19-1011.

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Mohammadi, Mahvelati Tara. « The Nod-like receptor, Nlrp12, plays an anti-inflammatory role in experimental autoimmune encephalomyelitis ». Mémoire, Université de Sherbrooke, 2017. http://hdl.handle.net/11143/11612.

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Abstract : Multiple Sclerosis (MS) is an organ-specific autoimmune disease characterized by the presence of demyelinating plaques throughout the central nervous system (CNS) as a result of an abnormal inflammatory response. During MS, activated microglia can play the role of antigen presenting cells and can, therefore, skew T cell responses towards a pro-inflammatory phenotype. Once activated, microglia upregulate the expression of pro-inflammatory molecules. In addition to microglial responses during MS, astrocytes are also implicated in the development of MS lesions. Upon injury and nearby neuronal death, astrocytes undergo astrogliosis. To date, several molecular pathways were identified as targets for therapeutic interventions for MS such as NF-kB & Nlrs. Nlrs are regulatory proteins of the immune system capable of regulating both innate and adaptive responses. Nlrp12 is a pyrin-containing intracellular protein, largely expressed in cells of myeloid origin. Nlrp12 plays an important role in immune inflammatory responses by negatively regulating the NF-κB pathway and modulatory roles, such as dendritic cell migration. The focus of this study was to evaluate the hypothesis where Nlrp12 plays an anti-inflammatory role in Experimental Autoimmune Encephalomyelitis (EAE), a well-characterized mouse model to study MS. Over a course of 9 weeks, Nlrp12 KO mice demonstrated increased severity in disease levels compared to WT mice. In both genotypes, the disease was observed to peak around the 3rd week post immunization A significant increase in Nlrp12 mRNA was observed in diseased WT compared to healthy WT mice. A significant increase in the expression of CCR5, COX-2, and IL-1 β in Nlrp12 KO mice relative to WT mice, was observed. Interestingly, no differences in the percentage of gliosis was seen at 3 weeks post injection in both genotypes, however after 9 weeks of diseases, in Nlrp12 KO mice we observed a significant increase in the percentage of reactive gliosis compared to WT mice. A significant activation of NF-kB-dependent inflammation was seen in primary microglial cell cultures from Nlrp12 KO relative to WT following LPS stimulation. Moreover, supernatants of analysis for the level of nitrates with Griess reagent and with ELISA for TNFα and IL-6, demonstrated an increase in the pro-inflammatory phenotype from microglia from Nlrp12 KO mice compared to WT mice. These results suggest a critical role of Nlrp12 in suppressing inflammation during the development of the disease given that in its absence, we observed an increase in the inflammatory response.
La sclérose en plaques est une maladie auto-immune déclenchée par une réaction inflammatoire anormale et caractérisée par la dégradation de myéline au niveau du système nerveux central. Durant la sclérose en plaques, la microglie promeut l’expression de molécules pro-inflammatoires et joue le rôle de cellules présentatrices d’antigènes pour forcer les cellules T à adopter un phénotype pro-inflammatoire. Outre les réponses associées à la microglie, les astrocytes sont aussi impliqués dans le développement des lésions. Jusqu’à présent, plusieurs voies moléculaires ont été identifiées comme cibles pour des interventions thérapeutiques tel que les voies de NF-kB et Nlrs. Les récepteurs Nlrs sont des protéines régulatrices du système immunitaire inné et adaptatif. Nlrp12 joue un rôle important dans les réponses inflammatoires immunes en régulant négativement la voie NF-kB et la migration de cellules dendritiques. L’objectif de cette étude est d’étudier l’hypothèse dans laquelle Nlrp12 joue un rôle anti-inflammatoire dans l’encéphalopathie expérimentale autoimmune (EAE), un modèle murin de la sclérose en plaques. Durant 9 semaines, des souris n’exprimant pas Nlrp12 ont démontré un état sévère de la maladie comparativement aux souris de type sauvage (WT). Dans les deux types de génotypes, la maladie était observée à son maximum autour de la 3ème semaine après immunisation. Une augmentation significative de l’expression d’ARNm de Nlrp12 était observée dans les souris contrôles malades comparativement aux souris saines. Une augmentation significative de l’expression de Ccr5, COX-2 ainsi qu’IL-1β était détectée dans les souris Nlrp12 KO par rapport aux souris WT. De plus, aucune différence dans le pourcentage de gliose était observée dans les deux génotypes à 3 semaines post-injection. Par contre, le pourcentage de gliose activée augmentait dans les souris Nlrp12 KO après 9 semaines de maladie. Nous avons remarqué une activation prononcée de l’inflammation dépendante de NF-kB dans des cultures cellulaires primaires de microglie provenant de souris Nlrp12 KO soumise à une stimulation au LPS. Finalement, la quantification des niveaux de nitrates et des cytokines TNFα et IL-6 traduisait une signature pro-inflammatoire de la microglie des souris Nlrp12 KO comparativement aux souris WT. Ces résultats suggèrent un rôle antiinflammatoire de Nlrp12 durant le développement de la sclérose en plaques considérant la réponse inflammatoire accrue en absence de Nlrp12.

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Sim, Deborah. « Dynamic Intravital Imaging of Immune Cells During the Initiating Events of Experimental Autoimmune Encephalomyelitis ». Case Western Reserve University School of Graduate Studies / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1396560202.

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Griffin, Ann Christine. « The influences of gender and neuroendocrine reactivity in the modulation of experimental autoimmune encephalomyelitis / ». The Ohio State University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487778663284975.

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Wu, Xingchen. « Multiple sclerosis : MRI diagnosis, potential treatment and future potential for nanoparticle applications / ». Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-515-1/.

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Martínez, Membrives Esther. « Susceptibility to experimental autoimmune encephalomyelitis (model of multiple sclerosis) and anxiety in genetically heterogeneous rats ». Doctoral thesis, Universitat Autònoma de Barcelona, 2012. http://hdl.handle.net/10803/123299.

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Las respuestas al estrés del eje hipotalámico-pituitario-adrenal (HPA) juegan un papel decisivo tanto en la conducta ansiosa como en el funcionamiento del sistema inmune (IS). Es sabido que los niveles elevados de glucocorticoides (GC) desempeñan un papel protector ante la encefalomielitis experimental autoinmune (EAE), fiable modelo animal de la esclerosis múltiple. En esta Tesis, nos propusimos investigar si un determinado perfil ansioso podría corresponderse con un perfil específico de sensibilidad a la inflamación. En el “Estudio I”, ratas genéticamente heterogéneas N/Nih-HS de ambos sexos fueron inmunizadas con proteína oligodendrocito de la mielina (MOG) para evaluar la EAE. Con el objetivo de valorar los efectos de la ansiedad sobre el IS, examinamos la incidencia (INC) y la severidad de la EAE que presentaban los subgrupos de ratas con puntuaciones extremas en ansiedad. De estos subgrupos (de baja y alta ansiedad) también se comparó la conducta ansiosa y el peso relativo de las glándulas adrenales (RAW). Los resultados indicaron una posible relación entre alta ansiedad y resistencia a la EAE. Sin embargo, algunas de las asociaciones asumidas en el “Estudio I” entre conducta ansiosa y estrés fisiológico, debían esclarecerse. Para ello, en el “Estudio II” se estudiaron las posibles relaciones entre las respuestas del eje HPA y la ansiedad las ratas inbred DA y PVG de ambos sexos. Las cepas DA y PVG son respectivamente susceptible y resistente a un amplio espectro de enfermedades autoinmunes, entre otras, la EAE. En el presente estudio, se caracterizaron estas cepas por sus conductas de miedo/ansiedad y actividad ante la novedad. Además se examinó la function del eje HPA, en terminos de niveles de corticosterona (basal y post-stress), peso relativo de las glándulas adrenales, y su expresión mRNA del receptor de la hormona adrenocorticotropa (MC2R). También se estudió la expresión mRNA de CD74 (complejo mayor de histocompatibilidad, clase II); y la interleucina proinflamatoria-6 (IL-6), en el núcleo paraventricular del hipotálamo, la pituitaria y las adrenales. En conjunto, nuestros resultados muestran que en la EAE, un perfil ansioso se correspondería con un eje HPA incrementado, que podría actuar reprimiendo las respuestas inflamatorias, produciendo un efecto de cierta resistencia a la EAE.
Stress hypothalamic-pituitary-adrenal (HPA) axis responses play a role in both anxiety behaviour and immune system (IS). Enhanced glucocorticoid (GC) levels have shown to play a protective role in experimental autoimmune encephalomyelitis (EAE), a reliable animal model of multiple sclerosis. In this Thesis, we aimed to investigate if a determined anxious profile could correspond to a specific inflammatory susceptibility. In “Study I”, genetically heterogeneous N/Nih-HS rats of both sexes were immunized with myelin oligodendrocyte glycoprotein (MOG) to evaluate EAE. To assess the effect of anxiety on IS, subgroups of rats scoring extreme values of anxiety were examined on their EAE incidence (INC) and severity. Also, anxious behaviour and relative adrenal weight (RAW) of subgroups selected by resistance or susceptibility was studied was compared. Results indicated a possible relationship between high anxiety and EAE-resistance. However, the assumed associations between behavioural anxiety and physiological stress needed to be elucidated. Thus, in “Study II” we studied in male and female DA and PVG inbred rats the possible relationships among HPA axis responses and anxiety. DA and PVG strains are respectively susceptible and resistant to a wide range of experimental autoimmune diseases, EAE among others. In the current study, these strains were characterized by their anxiety/inhibition. We further examined their HPA axis function, by means of (basal and post-stress) corticosterone levels, RAW, and via RT–PCR their expression of mRNA adrenocorticotropin receptor (Melanocortin 2 Receptor, MC2R) on adrenal glands. We also studied the mRNA expression of both CD74 (major histocompatibility complex; MHC-II) and the pro-inflammatory interleukin-6 (IL-6) on paraventricular nucleus of the hypothalamus (PVN), pituitary and adrenal glands. Together, our data show that in EAE, a high anxious profile accompanied by an enhanced HPA axis may involve the repression of inflammatory responses, providing a certain resistance.

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Berard, Jennifer. « Immune mediators involved in the differential pathogenesis of relapsing-remitting and chronic experimental autoimmune encephalomyelitis ». Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=92223.

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Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is characterized by inflammation, demyelination, and axonal loss. These characteristic histopathological features of MS are similar to those seen in the animal model experimental autoimmune encephalomyelitis (EAE), a T cell-mediated demyelinating disease. Importantly, many of the immune mediators involved in EAE pathogenesis have also been implicated in MS. Like MS, EAE is a heterogeneous disease that can follow either a relapsing-remitting or a chronic disease course. However, the molecular and pathogenic differences which underlie the development of these distinct forms of disease are poorly understood. To better understand these differences, I characterized models of relapsing-remitting and chronic EAE. To carry out this work, I first developed models of these forms of disease that could be induced on the same genetic background using the same myelin antigen, thereby removing confounding variables from the study. I then characterized the histopathological features and immune cell profile of these EAE models at several stages of disease (Chapter 2). These analyses revealed that chronic EAE was associated with increased tissue damage, as well as with an enhanced CD8+ T cell response. In addition, the expression of several pro-inflammatory cytokines was increased in chronic relative to relapsing-remitting EAE. This differential cytokine response led to the assessment of the expression and role of 'suppressor of cytokine signalling 1' (SOCS1) in these two forms of disease (Chapter 3). SOCS1 is a known negative regulator of cytokine receptor signalling, and at the peak stage of disease, SOCS1 expression was increased in relapsing-remitting compared to chronic EAE, suggesting that it may play a role in promoting remission. The beneficial effect of SOCS1 was confirmed by additional work which showed that administration of a SOCS1-mimetic peptide reduced disease severity in anima
La sclérose en plaques (SEP) est une maladie du système nerveux central (CNS) qui se caractérise par l`inflammation, la démyélinisation, et la perte axonale. Ces traits histopathologiques caractéristiques de la SEP sont semblables à ceux aperçus dans le modèle animale de l'encéphalomyélite autoimmune expérimentale (EAE), une maladie démyélinisante induite par les lymphocytes T. Plus important encore, plusieurs des médiateurs immunitaires engagés dans la pathogenèse d'EAE ont été également impliqués dans la SEP. Tout comme la SEP, l'EAE est une maladie hétérogène qui peut prendre une forme cyclique (poussées et rémissions alternées) ou bien un cours chronique. Cependant, les différences moléculaires et pathogéniques qui sont à la base du développement de ces formes distinctes de la maladie sont mal comprises. Pour mieux comprendre ces différences, j'ai caractérisé des modèles de la forme cyclique (poussée-rémission) et de la forme chronique de l'EAE. Pour effectuer ce travail, j'ai d'abord développé des modèles de ces formes de la maladie pouvant être induits sur un même fond génétique, en utilisant le même antigène de myéline, supprimant ainsi les variabilités de l'étude qui peuvent mener à la confusion. J'ai ensuite caractérisé les particularités histopathologiques, ainsi que le profil cellulaire immunitaire de ces modèles de l'EAE à plusieurs étapes de la maladie (chapitre 2). Ces analyses ont révélé une association entre l`EAE chronique et une élévation des dommages tissulaires, ainsi qu'une augmentation de la réponse des cellules T CD8+. En outre, l'expression de plusieurs cytokines pro-inflammatoires a été augmentée dans l`EAE chronique en comparaison à celle de la forme cyclique. Cette réponse différentielle des cytokines a mené à l'évaluation de l'expression et du rôle de la famille des « suppresseurs du signal des cytokines » (SOCS) dans les deux formes de la maladie (cha

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Bibani, Rashid Hamid. « Exploring the neuroprotective and alerting effects of modafinil in multiple sclerosis and experimental autoimmune encephalomyelitis ». Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/13343/.

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Multiple sclerosis (MS) is the most common demyelinating disease. It is characterised by a great variety of neurological deficits, which most commonly present initially in a relapsing remitting fashion and then take on a gradually progressive course. MS is incurable, since present medications do not counteract progression of the disease. Therefore, an additional strategy aims to focus on prevention of the neuronal loss in an attempt to stop or slow down the progression of the disease. In this thesis the neuroprotective potential of modafinil is tested in MS in a retrospective study. The ability of modafinil to reduce neurological dysfunction in the MS animal model is also investigated. In retrospective study the expanded disability status scale (EDSS) progression of thirty patients with MS who received modafinil for the treatment of MS-related fatigue for an uninterrupted period of 3 years or more was compared with ninety matched patients not treated with modafinil, followed up for a matching period of time. We found that the EDSS increase in patients not treated with modafinil was greater than in those treated with modafinil in both relapsing/remitting and progressive MS. In another experiment, we evaluated the effect of two treatment doses (low dose and high dose) of modafinil on the level of disability in experimental autoimmune encephalomyelitis (EAE) in a placebo controlled study. Modafinil decreased the severity of EAE at both treatment doses and the effect was greater in high dose. The study in chapter 4 was aimed to explore the anti-fatigue and alerting effects of modafinil in MS in an attempt to link these with the potential neuroprotective effects of modafinil. This was a detailed reanalysis of a prospective placebo controlled study (based on prospectively collected data), in which we examined whether there is any difference between MS patients with fatigue, MS patients without fatigue, and healthy controls on measures of alertness and autonomic function. We found that MS patients with fatigue, compared with healthy controls, had reduced level of alertness on all the tests used, MS patients with fatigue had a reduced level of autonomic function compared to the other two groups. Furthermore, we found that Modafinil displayed alerting and sympathomimetic effects in all three groups of subjects. In Chapter 5, we assessed a problem relevant to the progression of MS. We take advantage of the methods and data used in the chapter 2 to apply the same retrospective study methodology and statistical retrospective modeling of EDSS progression using the linear regression model to look at the role of oligoclonal band (OCB) positivity or negativity in EDSS progression. Unlike previous studies in smaller cohorts, we did not find that OCB negative patients have a more benign course of disease. The meta-analysis study in chapter 6 was designed to generate some knowledge regarding the central mechanism of fatigue in general and fatigue related to MS, using a novel functional magnetic resonance imaging (fMRI) meta-analysis method developed by CR Tench in our group. The study has also aimed to explore the brain areas which could be activated by modafinil treatment. The conclusion of this study was that the thalamus and striate are central and relevant nodes for the pathogenesis of fatigue in MS. The study has not detected the specific brain area to be activated by modafinil and showed multiple brain activations. With regard to the promising findings in our previous experiments, the protocol of a prospective phase II clinical trial was designed and detailed in appendix 10 using radiological primary and clinical secondary outcome measures. In conclusion, modafinil may slow down the progression of disability in patients with MS and decrease disease severity in EAE. Modafinil can display alerting and sympathomimetic effects in MS patients as well as in healthy subjects. The thalamus and striate are central and relevant nodes for the pathogenesis of fatigue in MS. These are also areas affected by the MS gray matter pathology and may be targets for neuroprotection by modafinil in MS. Finally, we have not reported a significant difference in disease progression measured by EDSS and MSSS between OCB negative and OCB positive in our patients with MS. This seemingly heterogeneous group of experiments, primarily centred on modafinil’s potential as mechanistic therapy in MS, bring, I hope, new knowledge of aspects of disease progression and pharmacological neuroprotection in a stage of the disease where therapeutic options are currently limited and the need for new treatments is great.

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