Journal Article

Combined therapy with methylprednisolone and erythropoietin in a model of multiple sclerosis

Ricarda Diem, Muriel B. Sättler, Doron Merkler, Iris Demmer, Katharina Maier, Christine Stadelmann, Hannelore Ehrenreich and Mathias Bähr

in Brain

Published on behalf of The Guarantors of Brain

Volume 128, issue 2, pages 375-385
Published in print February 2005 | ISSN: 0006-8950
Published online December 2004 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awh365
Combined therapy with methylprednisolone and erythropoietin in a model of multiple sclerosis

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Neurodegenerative processes determine the clinical disease course of multiple sclerosis, an inflammatory autoimmune CNS disease that frequently manifests with acute optic neuritis. None of the established multiple sclerosis therapies has been shown to clearly reduce neurodegeneration. In a rat model of experimental autoimmune encephalomyelitis, we recently demonstrated increased neuronal apoptosis under methylprednisolone therapy, although CNS inflammation was effectively controlled. In the present study, we combined steroid treatment with application of erythropoietin to target inflammatory as well as neurodegenerative aspects. After immunization with myelin oligodendrocyte glycoprotein (MOG), animals were randomly assigned to six treatment groups receiving different combinations of erythropoietin and methylprednisolone, or respective monotherapies. After MOG-induced experimental autoimmune encephalomyelitis became clinically manifest, optic neuritis was monitored by recording visual evoked potentials. The function of retinal ganglion cells, the neurons that form the axons of the optic nerve, was measured by electroretinograms. Functional and histo pathological data of retinal ganglion cells and optic nerves revealed that neuron and axon protection was most effective when erythropoietin treatment that was started at immunization was combined with high-dose methylprednisolone therapy given from days 1 to 3 of MOG-induced experimental autoimmune encephalomyelitis. In contrast, isolated neuronal or axonal protection without clinical benefit was achieved under monotherapy with erythropoietin or methylprednisolone, respectively.

Keywords: methylprednisolone; erythropoietin; experimental autoimmune encephalomyelitis; neuroprotection; visual evoked potentials; AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; BDNF = brain-derived neurotrophic factor; CFA = complete Freund's adjuvant; EAE = experimental autoimmune encephalomyelitis; Epo = erythropoietin; ERG = electroretinogram; FG = fluorogold; IGF = insulin-like growth factor; MAPK = mitogen-activated protein kinase; MBP = myelin basic protein; MOG = myelin oligodendrocyte glycoprotein; MPred = methylprednisolone; RGC = retinal ganglion cell; VEP = visual evoked potential

Journal Article.  7838 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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