The Brown Norway opticospinal model of demyelination: Does it mimic multiple sclerosis or neuromyelitis optica?

• Published in: International journal of developmental neuroscience Vol. 30; no. 6; pp. 487 - 497
• Main Authors: Collongues, N., Chanson, J.B., Blanc, F., Steibel, J., Lam, C.D., Shabbir, A., Trifilieff, E., Honnorat, J., Pham-Dinh, D., Ghandour, M.S., de Seze, J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.10.2012
• Subjects: Animals; Aquaporin 4 - metabolism; Aquaporin-4; Brown Norway rat; Disease Models, Animal; Encephalitis - pathology; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - complications; Enzyme-Linked Immunosorbent Assay; Experimental autoimmune encephalomyelitis; Female; Gene Expression Regulation - physiology; Glial Fibrillary Acidic Protein - metabolism; Indexing in process; Magnetic Resonance Imaging; MOG; Multiple Sclerosis - pathology; Multiple Sclerosis - physiopathology; Myelin Basic Protein - metabolism; Myelin-Oligodendrocyte Glycoprotein - metabolism; Myelin-Oligodendrocyte Glycoprotein - toxicity; Neuromyelitis optica; Neuromyelitis Optica - chemically induced; Neuromyelitis Optica - metabolism; Neuromyelitis Optica - pathology; Optic Nerve - metabolism; Optic Nerve - pathology; Peptide Fragments - toxicity; Rats; Spinal Cord - metabolism; Spinal Cord - pathology; Statistics, Nonparametric; Time Factors; MOG; IFA; MS; EAE; Experimental autoimmune encephalomyelitis; Brown Norway rat; AQP4; Neuromyelitis optica; BN; GFAP; NMO; LFB/c; Aquaporin-4; OD; CSF; MBP; HE; ELISA; ON
• DOI: 10.1016/j.ijdevneu.2012.05.004
• ISSN: 0736-5748

► Periventricular area is involved in the Brown Norway MOG-induced opticospinal model of demyelination. ► Markers of astrocyte expression (AQP4 and GFAP) are significantly modified in opticospinal region and periventricular area. ► Disability scores were correlated with demyelination and inflammation but not with AQP4/GFAP expression. ► A neuromyelitis optica-phenotype was observed in this model but without any antibodies against AQP4. ► This model has characteristics of both opticospinal multiple sclerosis and neuromyelitis optica. Opticospinal demyelinating diseases in humans are mostly characterized by the opticospinal form of multiple sclerosis (MS) and neuromyelitis optica (NMO). Increasing attention has recently focused on astrocyte markers, aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) in these diseases. We induced opticospinal demyelination in Brown Norway rats with soluble recombinant rat myelin oligodendrocyte glycoprotein (1–116) and incomplete Freund's adjuvant. Clinical, MRI, neuropathological and immunological evaluations were performed, with a focus on AQP4 and GFAP. We confirmed the opticospinal phenotype, including extensive myelitis, but also showed the MRI-characterized involvement of the periventricular area. Expression levels of myelin, AQP4 and GFAP showed the early involvement of astrocytes before demyelination in the optic nerve. The overexpression of AQP4 was particularly pronounced in the spinal cord and was concomitant with demyelination and astrocyte apoptosis. The disability scores were correlated with demyelination and inflammation but not with AQP4/GFAP expression. No antibodies against the linear and conformational epitopes of AQP4 were detected. Whereas a NMO-like phenotype was observed in this model, the AQP4/GFAP expression during the disease process was more closely related to opticospinal MS than NMO. However, this model raises the question of a continuum between opticospinal MS and the seronegative NMO subtype.