The Brown Norway opticospinal model of demyelination: does it mimic multiple sclerosis or 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.
Laboratoire d'Imagerie et de Neurosciences Cognitives, UMR 7237 CNRS/UDS, Université de Strasbourg, Faculté de Médecine, 4 Rue Kirschleger, Strasbourg, France. nicolas.collongues@chru-Strasbourg.fr
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N
Collongues
J B
JB
Chanson
F
F
Blanc
J
J
Steibel
C D
CD
Lam
A
A
Shabbir
E
E
Trifilieff
J
J
Honnorat
D
D
Pham-Dinh
M S
MS
Ghandour
J
J
de Seze
D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000150:complications; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000473:pathology / Q000503:physiopathology*; D004676:Myelin Basic Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000378:metabolism / Q000633:toxicity; D009471:Neuromyelitis Optica / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000633:toxicity; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D018709:Statistics, Nonparametric; D013997:Time Factors
C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments