Autoimmune optic neuritis in the common marmoset monkey: Comparison of visual evoked potentials with MRI and histopathology
Ricarda Diem 1*,
Iris Demmer 2,
Susann Boretius 3,
Doron Merkler 4,
Barthel Schmelting 5,
Sarah Katharine Williams 1,
Muriel Barbara Saettler 2,
Mathias Baehr 6,
Thomas Michaelis 3,
Jens Frahm 3,
Wolfgang Brueck 7,
and
Eberhard Fuchs 8
1 Neurologische Klinik der Universitaet des Saarlandes, Homburg/Saar, Germany
2 Neurologie, Georg-August-Universitaet Goettingen, Goettingen, Germany
3 Biomedizinische NMR Forschungs GmbH, Max-Planck-Institut fuer biophysikalische Chemie, Goettingen, Germany
4 Neuropathologie, Georg-August-Universitaet Goettingen, Goettingen, Germany
5 Klinische Neurobiologie, Deutsches Primatenzentrum, Goettingen, Germany
6 Neurologie, Georg-August-Universitaet Goettingen, Goettingen, Germany; Institut fuer Multiple-Sklerose-Forschung, Universitaetsmedizin der Georg-August-Universitaet und Gemeinnuetzige Hertie-Stiftung, Goettingen, Germany
7 Neuropathologie, Georg-August-Universitaet Goettingen, Goettingen, Germany; Institut fuer Multiple-Sklerose-Forschung, Universitaetsmedizin der Georg-August-Universitaet und Gemeinnuetzige Hertie-Stiftung, Goettingen, Germany
8 Neurologie, Georg-August-Universitaet Goettingen, Goettingen, Germany; Klinische Neurobiologie, Deutsches Primatenzentrum, Goettingen, Germany; Institut fuer Multiple-Sklerose-Forschung, Universitaetsmedizin der Georg-August-Universitaet und Gemeinnuetzige Hertie-Stiftung, Goettingen, Germany
* To whom correspondence should be addressed. E-mail: ricarda.diem{at}uniklinikum-saarland.de.
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Abstract |
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Purpose: The aim of this study was to assess the use of visual evoked potentials (VEPs) for the in vivo detection of impaired visual function in a marmoset model of multiple sclerosis. The sensitivity of the VEP recordings was determined by a comparison with magnetic resonance imaging (MRI) and histopathology.
Methods: Baseline VEPs were recorded from 6 healthy marmoset monkeys in response to flash light stimulation. Experimental autoimmune encephalomyelitis (EAE) was induced in 4 of the 6 monkeys. Clinical scores were assessed daily, while VEPs were recorded every second week. In vivo MRI and subsequent histopathology of the brains and optic nerves were performed at the end of the study.
Results: After induction of EAE, all 4 marmosets developed clinical signs between day 26 and 38 post immunization. VEPs were normal during the induction phase of the disease, but deteriorated in amplitude with the occurrence of clinical symptoms in all animals. MRI revealed bilateral optic neuritis as well as signal alterations in the optic tracts and occipital sub-cortical white matter in 2 of the animals. In the remaining 2 animals, MRI detected signal alterations in occipital sub-cortical white matter. Histopathological results were concordant with the MRI findings.
Conclusions: VEPs are an easily accessible non-invasive tool for measuring visual function and diagnosing impairment of the visual pathway in a marmoset EAE model.
Key Words:
Experimental autoimmune encephalomyelitis, visual evoked potentials, marmoset, optic neuritis, magnetic resonance imaging
