Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Üçal, M; Haindl, MT; Adzemovic, MZ; Strasser, J; Theisl, L; Zeitelhofer, M; Kraitsy, K; Ropele, S; Schäfer, U; Fazekas, F; Hochmeister, S.
Widespread cortical demyelination of both hemispheres can be induced by injection of pro-inflammatory cytokines via an implanted catheter in the cortex of MOG-immunized rats.
Exp Neurol. 2017; 294(7):32-44
Doi: 10.1016/j.expneurol.2017.04.014
Web of Science
PubMed
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FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Haindl Michaela Tanja
- Hochmeister Sonja
- Ücal Muammer
- Co-Autor*innen der Med Uni Graz
- Fazekas Franz
- Kraitsy Klaus
- Ropele Stefan
- Schäfer Ute
- Strasser Johannes
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- Abstract:
- Cortical demyelination is a common finding in patients with chronic multiple sclerosis (MS) and contributes to disease progression and overall disability. The exact pathomechanism that leads to cortical lesions is not clear. Research is limited by the fact that standard animal models of multiple sclerosis do not commonly affect the cortex, or if they do in some variants, the cortical demyelination is rather sparse and already remyelinated within a few days. In an attempt to overcome these limitations we implanted a tissue-compatible catheter into the cortex of Dark Agouti rats. After 14days the rats were immunized with 5μg myelin oligodendrocyte glycoprotein (MOG) in incomplete Freund's Adjuvant, which did not cause any clinical signs but animals developed a stable anti-MOG antibody titer. Then the animals received an injection of proinflammatory cytokines through the catheter. This led to a demyelination of cortical and subcortical areas starting from day 1 in a cone-like pattern spreading from the catheter area towards the subarachnoid space. On day 3 cortical demyelination already expanded to the contralateral hemisphere and reached its peak between days 9-15 after cytokine injection with a widespread demyelination of cortical and subcortical areas of both hemispheres. Clinically the animals showed only discrete signs of fatigue and recovered completely after day 15. Even on day 30 we still were able to detect demyelination in subpial and intracortical areas along with areas of partial and complete remyelination. Loss of cortical myelin was accompanied with marked microglia activation. A second injection of cytokines through the catheter on day 30 led to a second demyelination phase with the same symptoms, but again no detectable motor dysfunction. Suffering of the animals appeared minor compared to standard Experimental Autoimmune Encephalomyelitis and therefore, even long-term observation and repeated demyelination phases seem ethically acceptable. Copyright © 2017 Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Calcium-Binding Proteins - metabolism
- Caspase 3 - metabolism
- Cerebral Cortex - pathology
- Cytokines - metabolism
- Cytokines - toxicity
- Demyelinating Diseases - chemically induced
- Demyelinating Diseases - pathology
- Disease Models, Animal -
- Encephalomyelitis, Autoimmune, Experimental - chemically induced
- Encephalomyelitis, Autoimmune, Experimental - diagnostic imaging
- Encephalomyelitis, Autoimmune, Experimental - immunology
- Encephalomyelitis, Autoimmune, Experimental - pathology
- Fibrin - metabolism
- Freund's Adjuvant - adverse effects
- Functional Laterality - drug effects
- Functional Laterality - physiology
- Immunization - adverse effects
- Lipids - adverse effects
- Male -
- Microfilament Proteins - metabolism
- Microscopy, Confocal -
- Motor Activity -
- Myelin Proteolipid Protein - metabolism
- Myelin-Associated Glycoprotein - adverse effects
- Myelin-Associated Glycoprotein - blood
- Nerve Tissue Proteins - metabolism
- Rats -
- Statistics, Nonparametric -
- Find related publications in this database (Keywords)
- Progressive multiple sclerosis
- Cortical demyelination
- Neuroimmunology
- Neuroinflammation
- Animal model