title: Spatial diversity of blood-brain barrier alteration and macrophage invasion in experimental autoimmune encephalomyelitis: a comparative MRI study.
abstract: Inflammation plays a central role in the development of numerous disorders of the central nervous system (CNS) such as multiple sclerosis (MS). For a long time it was assumed that recruitment of macrophages into the CNS and breakdown of the blood-brain barrier (BBB) are closely linked. In the present study we challenge this concept. We used small superparamagnetic iron oxide particles (SPIO)-enhanced T2-weighted (T2-w) magnetic resonance imaging (MRI) on a routine 1.5 T MRI unit to follow macrophage infiltration in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. After an initial SPIO-enhanced MRI, gadofluorine M (Gf), an experimental contrast agent which proved to be more sensitive in detecting BBB leakage than gadolinium (Gd)-DTPA (Bendszus, M., Ladewig, G., Jestaedt, L., Misselwitz, B., Solymosi, L., Toyka, K.V., Stoll, G., Gadofluorine-M enhancement allows more sensitive detection of inflammatory CNS lesions than T2-w imaging: a quantitative MRI study. Brain 2008; 1-12), was applied to the same animals followed by a second scan. Areas with SPIO-induced signal loss on T2-w MRI indicative of recent macrophage infiltration were matched with areas showing Gf enhancement as a measure of BBB disturbance. Overall 87 EAE lesions showed iron-related signal loss, while 57 lesions showed Gf enhancement. By direct comparison we could detect concomitant SPIO-induced signal loss and Gf enhancement only in a small minority of lesions. In conclusion, our findings show macrophage infiltration in the CNS during EAE in areas with a closed BBB for humoral factors. This holds true despite the use of a more sensitive MR contrast agent for BBB disruption than Gd-DTPA. Our experimental observations may have implications for disease monitoring in MS patients by MRI which guides treatment decisions.
authors.affiliation: Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany.
authors.forename: Gesa
authors.initials: G
authors.lastname: Ladewig
authors.forename: Leonie
authors.initials: L
authors.lastname: Jestaedt
authors.forename: Bernd
authors.initials: B
authors.lastname: Misselwitz
authors.forename: Laszlo
authors.initials: L
authors.lastname: Solymosi
authors.forename: Klaus
authors.initials: K
authors.lastname: Toyka
authors.forename: Martin
authors.initials: M
authors.lastname: Bendszus
authors.forename: Guido
authors.initials: G
authors.lastname: Stoll
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000503:physiopathology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003287:Contrast Media; D004195:Disease Models, Animal; D018450:Disease Progression; D004660:Encephalitis / Q000473:pathology / Q000503:physiopathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D005290:Ferric Compounds; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D009103:Multiple Sclerosis / Q000473:pathology / Q000503:physiopathology; D009942:Organometallic Compounds; D011237:Predictive Value of Tests; D051381:Rats; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D009942:Organometallic Compounds; C477144:gadofluorine; C000499:ferric oxide