title: Mouse model mimics multiple sclerosis in the clinico-radiological paradox.
abstract: The value of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, in deriving novel diagnostic and therapeutic input has been subject to recent debate. This study is the first to report a disseminated distribution of plaques including cranial nerves, prior to or at early stages of disease in murine adoptive transfer EAE, irrespective of the development of clinical symptoms. We induced EAE by adoptive proteolipid protein-specific T-cell transfer in 26 female SJL/J mice, and applied high-field-strength magnetic resonance imaging (MRI) scans longitudinally, assessing blood-brain barrier (BBB) disruption by gadopentate dimeglumine enhancement. We visualized inflammatory nerve injury by gadofluorine M accumulation, and phagocytic cells in inflamed tissue by very small anionic iron oxide particles (VSOP-C184). MRI was correlated with immunohistological sections. In this study, we discovered very early BBB breakdown of white and grey brain matter in 25 mice; one mouse developed exclusively spinal cord inflammation. Widely disseminated contrast-enhancing lesions preceded the onset of disease in 10 animals. Such lesions were present despite the absence of any clinical disease formation in four mice, and coincided with the first detectable symptoms in others. Cranial nerves, predominantly the optic and trigeminal nerves, showed signal intensity changes in nuclei and fascicles of 14 mice. At all sites of MRI lesions we detected cellular infiltrates on corresponding histological sections. The discrepancy between the disease burden visualized by MRI and the extent of disability indeed mimics the human clinico-radiological paradox. MRI should therefore be implemented into evaluational in vivo routines of future therapeutic EAE studies.
authors.affiliation: Cecilie-Vogt-Clinic for Molecular Neurology, Charité - University Medicine Berlin, and Max-Delbrueck-Center for Molecular Medicine, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wuerfel
authors.forename: Eva
authors.initials: E
authors.lastname: Tysiak
authors.forename: Timour
authors.initials: T
authors.lastname: Prozorovski
authors.forename: Maureen
authors.initials: M
authors.lastname: Smyth
authors.forename: Susanne
authors.initials: S
authors.lastname: Mueller
authors.forename: Joerg
authors.initials: J
authors.lastname: Schnorr
authors.forename: Matthias
authors.initials: M
authors.lastname: Taupitz
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D003287:Contrast Media; D003391:Cranial Nerves / Q000473:pathology; D004195:Disease Models, Animal; D004705:Endocytosis / Q000502:physiology; D005260:Female; D005466:Fluorocarbons; D019786:Gadolinium DTPA; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D017628:Microglia / Q000473:pathology; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000473:pathology*; D009942:Organometallic Compounds; D010587:Phagocytosis / Q000187:drug effects; D011859:Radiography; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D009942:Organometallic Compounds; C517961:gadofluorine M; D019786:Gadolinium DTPA