Histopathological characterization of magnetic resonance imaging-detectable brain white matter lesions in a primate model of multiple sclerosis: a correlative study in the experimental autoimmune encephalomyelitis model in common marmosets (Callithrix jacchus).
Experimental autoimmune encephalomyelitis in the common marmoset, a nonhuman primate species (Callithrix jacchus), is a new model for multiple sclerosis. Given the close immunological relationship between marmosets and humans, it is an attractive model for investigating immunopathological pathways relevant to multiple sclerosis and to evaluate new treatments for the disease. Unlike in the originally documented model, experimental autoimmune encephalomyelitis induced without the use of Bordetella pertussis led to a chronic disease of moderate severity. The clinical course of experimental autoimmune encephalomyelitis in the present model was mainly chronic and progressive, but periods of incomplete remission did occur. At the chronic stage of the disease, actively demyelinating lesions were found together with inactive demyelinated and remyelinated (shadow) plaques. Before immunization and during clinically active experimental autoimmune encephalomyelitis, T1- and T2-weighted magnetic resonance brain images were obtained. Correlation of the data from the magnetic resonance images and the neuropathology analysis revealed that the hyperintense regions in T2-weighted images represented both active and inactive remyelinating lesions. Quantification showed that the number of lesions in T2-weighted magnetic resonance images equalled those found by pathological examination, and thus T2-weighted magnetic resonance imaging can be used to discern the total lesion load. Extravasation of gadolinium-diethylenetriamine-penta-acetic acid (triple dose) was found only in lesions, which by histopathology were shown to be engaged in the process of active demyelination.
Hart
B A
BA
Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands. hart@bprc.nl
Bauer
J
J
Muller
H J
HJ
Melchers
B
B
Nicolay
K
K
Brok
H
H
Bontrop
R E
RE
Lassmann
H
H
Massacesi
L
L
D000818:Animals; D001921:Brain / Q000473:pathology*; D002144:Callithrix; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000473:pathology*; D009185:Myelin Proteins / Q000276:immunology / Q000494:pharmacology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology
D009185:Myelin Proteins