Combined therapy with methylprednisolone and erythropoietin in a model of multiple sclerosis.
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.
Diem
Ricarda
R
Neurologische Universitätsklinik, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany. rdiem@gwdg.de
Sättler
Muriel B
MB
Merkler
Doron
D
Demmer
Iris
I
Maier
Katharina
K
Stadelmann
Christine
C
Ehrenreich
Hannelore
H
Bähr
Mathias
M
D000818:Animals; D004359:Drug Therapy, Combination; D004596:Electroretinography; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004921:Erythropoietin / Q000627:therapeutic use*; D005074:Evoked Potentials, Visual; D005260:Female; D008775:Methylprednisolone / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009900:Optic Nerve / Q000473:pathology / Q000503:physiopathology; D009902:Optic Neuritis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D011914:Rats, Inbred BN; D011994:Recombinant Proteins; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000502:physiology; D015398:Signal Transduction
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D008775:Methylprednisolone