Medizinische Universität Graz - Research portal
Selected Publication:
Diem, R; Hobom, M; Maier, K; Weissert, R; Storch, MK; Meyer, R; Bähr, M.
Methylprednisolone increases neuronal apoptosis during autoimmune CNS inflammation by inhibition of an endogenous neuroprotective pathway.
J Neurosci. 2003; 23(18):6993-7000
Doi: 10.1523/JNEUROSCI.23-18-06993.2003
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- Co-authors Med Uni Graz
- Storch Maria
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- Abstract:
- Optic neuritis is one of the most common clinical manifestations of multiple sclerosis (MS), a chronic inflammatory disease of the CNS. High-dosage methylprednisolone treatment has been established as the standard therapy of acute inflammation of the optic nerve (ON). The rationale for corticosteroid treatment lies in the antiinflammatory and immunosuppressive properties of these drugs, as shown in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. To investigate the influence of methylprednisolone therapy on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the ON, we used a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Optic neuritis was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. Methylprednisolone treatment significantly increased RGC apoptosis during MOG-EAE. By Western blot analysis, we identified the underlying molecular mechanism: a suppression of mitogen-activated protein kinase (MAPK) phosphorylation, which is a key event in an endogenous neuroprotective pathway. The methylprednisolone-induced inhibition of MAPK phosphorylation was calcium dependent. Hence, we provide evidence for negative effects of steroid treatment on neuronal survival during chronic inflammatory autoimmune disease of the CNS, which should result in a reevaluation of the current therapy regimen.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis - drug effects
- Blotting, Western - drug effects
- Calcium - metabolism
- Calcium Channels - metabolism
- Cell Count - metabolism
- Cell Survival - drug effects
- Central Nervous System - drug effects
- Disease Models, Animal - drug effects
- Electroretinography - drug effects
- Encephalomyelitis, Autoimmune, Experimental - chemically induced
- Enzyme Inhibitors - pharmacology
- Evoked Potentials, Visual - drug effects
- Female - drug effects
- Methylprednisolone - adverse effects
- Mitogen-Activated Protein Kinases - antagonists and inhibitors
- Myelin-Associated Glycoprotein - antagonists and inhibitors
- Neurons - drug effects
- Optic Neuritis - chemically induced
- Phosphorylation - drug effects
- Rats - drug effects
- Rats, Inbred BN - drug effects
- Retinal Ganglion Cells - drug effects
- Signal Transduction - drug effects
- Find related publications in this database (Keywords)
- experimental autoimmune encephalomyelitis
- glucocorticosteroids
- retinal ganglion cells
- visual evoked potentials
- electroretinogram
- mitogen-activated kinases