The astrocytic response in early experimental autoimmune encephalomyelitis occurs across both the grey and white matter compartments

Pham, Hong; Ramp, Anton A.; Klonis, Nectarios; Ng, Sze Woei; Klopstein, Armelle; Ayers, Margaret; Orian, Jacqueline M.

doi:10.1016/j.jneuroim.2008.12.010

Cited by 29 publications

(19 citation statements)

References 44 publications

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“…However, the use of the C57Bl/6 variant is complicated by the occurrence of multiple clinical profiles (chronic, multiphasic or monophasic) and unpredictability of disease course within a given cohort (Berard et al 2010;Bernard et al 1998). Additionally, we have shown that the pathology in this variant is associated with a progressively diminishing astrogliosis with increasing clinical score, a feature which is not associated with MS pathology (Ayers et al 2004;Onuki et al 2001;Pham et al 2009Pham et al , 2011Wang et al 2005). The use of transgenic and gene deletion mutants in the NOD/Lt background in a number of investigations (Anderson et al 2012;Cannon et al 2008;Mars et al 2002Mars et al , 2008McQualter et al 2001) suggests that generation of such genetically modified strains does not present any particular technical difficulty.…”

Section: Future Studiesmentioning

confidence: 81%

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Modelling MS: Chronic-Relapsing EAE in the NOD/Lt Mouse Strain

Dang

Bui

D'Souza

et al. 2015

Emerging and Evolving Topics in Multiple Sclerosis Pathogenesis and Treatments

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Modelling complex disorders presents considerable challenges, and multiple sclerosis (MS) is no exception to this rule. The aetiology of MS is unknown, and its pathophysiology is poorly understood. Moreover, the last two decades have witnessed a dramatic revision of the long-held view of MS as an inflammatory demyelinating white matter disease. Instead, it is now regarded as a global central nervous system (CNS) disorder with a neurodegenerative component. Currently, there is no animal model recapitulating MS immunopathogenesis. Available models are based on autoimmune-mediated demyelination, denoted experimental autoimmune encephalomyelitis (EAE) or virally or chemically induced demyelination. Of these, the EAE model has been the most commonly used. It has been extensively improved since its first description and now exists as a number of variants, including genetically modified and humanized versions. Nonetheless, EAE is a distinct disease, and each variant models only certain facets of MS. Whilst the search for more refined MS models must continue, it is important to further explore where mechanisms underlying EAE provide proof-of-principle for those driving MS pathogenesis. EAE variants generated with the myelin component myelin oligodendrocyte glycoprotein (MOG) have emerged as the preferred ones, because in this particular variant disease is associated with both T- and B-cell effector mechanisms, together with demyelination. MOG-induced EAE in the non-obese diabetic (NOD) mouse strain exhibits a chronic-relapsing EAE clinical profile and high disease incidence. We describe the generation of this variant, its contribution to the understanding of MS immune and pathogenetic mechanisms and potential for evaluation of candidate therapies.

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Section: Future Studiesmentioning

confidence: 81%

“…The antigen is delivered in two s.c. injections in the inguinal region and is followed by two i.v. injections of PTx at days 0 and 2, of 350 ng each (Wang et al 2005;Pham et al 2009Pham et al , 2011. Vehicle-only control mice receive the same treatment, but with the omission of MOG peptide.…”

Section: Clinical Profile and Lesion Topography In Mog 35-55 -Inducedmentioning

confidence: 99%

Modelling MS: Chronic-Relapsing EAE in the NOD/Lt Mouse Strain

Dang

Bui

D'Souza

et al. 2015

Emerging and Evolving Topics in Multiple Sclerosis Pathogenesis and Treatments

Self Cite

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“…Thus far, no BBB leakage has been demonstrated in GMLs and no significant complement deposition in GMLs has been observed . Additionally, the diameter of the blood vessels within lesions was found to be increased in WMLs, whereas this increase was less within GMLs …”

Section: Explanations For Pathological Cellular Differences Between Wmentioning

confidence: 89%

Pathological differences between white and grey matter multiple sclerosis lesions

Prins¹,

Schul²,

Geurts³

et al. 2015

Annals of the New York Academy of Sciences

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Multiple sclerosis (MS) is a debilitating disease characterized by demyelination of the central nervous system (CNS), resulting in widespread formation of white matter lesions (WMLs) and grey matter lesions (GMLs). WMLs are pathologically characterized by the presence of immune cells that infiltrate the CNS, whereas these immune cells are barely present in GMLs. This striking pathological difference between WMLs and GMLs raises questions about the underlying mechanism. It is known that infiltrating leukocytes contribute to the generation of WMLs; however, since GMLs show a paucity of infiltrating immune cells, their importance in GML formation remains to be determined. Here, we review pathological characteristics of WMLs and GMLs, and suggest some possible explanations for the observed pathological differences. In our view, cellular and molecular characteristics of WM and GM, and local differences within WMLs and GMLs (in particular, in glial cell populations and the molecules they express), determine the pathway to demyelination. Further understanding of GML pathogenesis, considered to contribute to chronic MS, may have a direct impact on the development of novel therapeutic targets to counteract this progressive neurological disorder.

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Section: Future Studiesmentioning

confidence: 81%

Emerging and Evolving Topics in Multiple Sclerosis Pathogenesis and Treatments

Flamme¹,

Orian²

2015

Current Topics in Behavioral Neurosciences

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Current Topics in Behavioral Neurosciences provides critical and comprehensive discussions of the most significant areas of behavioral neuroscience research, written by leading international authorities. Each volume offers an informative and contemporary account of its subject, making it an unrivalled reference source. Titles in this series are available in both print and electronic formats.With the development of new methodologies for brain imaging, genetic and genomic analyses, molecular engineering of mutant animals, novel routes for drug delivery, and sophisticated cross-species behavioral assessments, it is now possible to study behavior relevant to psychiatric and neurological diseases and disorders on the physiological level. The Behavioral Neurosciences series focuses on ''translational medicine'' and cutting-edge technologies. Preclinical and clinical trials for the development of new diagnostics and therapeutics as well as prevention efforts are covered whenever possible.

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The astrocytic response in early experimental autoimmune encephalomyelitis occurs across both the grey and white matter compartments

Cited by 29 publications

References 44 publications

Modelling MS: Chronic-Relapsing EAE in the NOD/Lt Mouse Strain

Modelling MS: Chronic-Relapsing EAE in the NOD/Lt Mouse Strain

Pathological differences between white and grey matter multiple sclerosis lesions

Emerging and Evolving Topics in Multiple Sclerosis Pathogenesis and Treatments

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