MRI-based monitoring of inflammation and tissue damage in acute and chronic relapsing EAE.
Experimental autoimmune encephalomyelitis (EAE) is a commonly used animal model that in several respects mimics human multiple sclerosis (MS), and can be used to design or validate new strategies for treatment of this disease. In the present study, different MRI techniques (macrophage tracking based on labeling cells in vivo by ultrasmall particles of iron oxide (USPIO), blood-brain barrier (BBB) breakdown, and magnetization transfer imaging (MTI)), as well as immunohistological staining were used to study the burden of disease in Lewis rats immunized by guinea pig myelin. The resulting imaging data was compared with behavioral readouts. Animals were studied during the acute phase and the first relapse. Activated monocytes were detected during both episodes in the brain stem or cortex. These areas coincided in part with areas of BBB breakdown. Significant changes of the magnetization transfer ratios (MTRs) of up to 35% were observed in areas of USPIO accumulation. This suggests that infiltrating monocytes are the major source of demyelination in EAE, but monocyte infiltration and breakdown of the BBB are temporally or spatially independent inflammatory processes.
Rausch
M
M
Novartis Institute for Biomedical Research, Basel, Switzerland. martin.rausch@pharma.novartis.com
Hiestand
P
P
Baumann
D
D
Cannet
C
C
Rudin
M
M
D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000473:pathology*; D002908:Chronic Disease; D003287:Contrast Media; D003911:Dextrans; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology* / Q000503:physiopathology; D052203:Ferrosoferric Oxide; D006571:Heterocyclic Compounds; D007089:Image Enhancement; D007249:Inflammation / Q000473:pathology; D007501:Iron; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D009000:Monocytes / Q000473:pathology; D009103:Multiple Sclerosis / Q000473:pathology; D009942:Organometallic Compounds; D010087:Oxides; D017933:Peripheral Nervous System / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence
D003287:Contrast Media; D003911:Dextrans; D006571:Heterocyclic Compounds; D058185:Magnetite Nanoparticles; D009942:Organometallic Compounds; D010087:Oxides; C097921:ferumoxtran-10; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D007501:Iron; D052203:Ferrosoferric Oxide