title: Partial inhibition of AT-EAE by an antibody to ICAM-1: clinico-histological and MRI studies.
abstract: The role of quantitative proton magnetic resonance imaging (MRI) for the evaluation of immunopathological lesions in the CNS was studied in adoptively transferred experimental allergic encephalomyelitis (AT-EAE). We utilized a recently established treatment model, inhibition of the cell adhesion molecule ICAM-1 by the monoclonal antibody 1A-29. The animals were scanned on days 3, 5 and 7 after injection of encephalitogenic T-cells, before and after bolus injection of Gd-DTPA by performing T1-measurements to assess the integrity of the blood-brain barrier (BBB). On day 7, immunohistochemistry was performed looking for T-cells, activated macrophages, and albumin staining. There was clinical evidence of partial inhibition of AT-EAE in rats treated with antibodies against ICAM-1. This finding was in line with a significantly reduced number of T-cells in the medulla. However, the number of activated macrophages and the distribution of albumin did not differ from untreated AT-EAE animals. The histological findings are in agreement with the MRI data before and after Gd-DTPA injection which were similar in treated and untreated AT-EAE rats on day 3 and 5. On day 7 after Gd-DTPA injection there was evidence of a delayed breakdown of the BBB in the treated rats. The observation of a dissociation of clinical and MRI findings, especially evidence of Gd-enhancement despite clinical improvement, may be important in the context of interpreting MRI studies in MS patients in treatment trials.
authors.affiliation: Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
authors.forename: S P
authors.initials: SP
authors.lastname: Morrissey
authors.forename: R
authors.initials: R
authors.lastname: Deichmann
authors.forename: J
authors.initials: J
authors.lastname: Syha
authors.forename: C
authors.initials: C
authors.lastname: Simonis
authors.forename: U
authors.initials: U
authors.lastname: Zettl
authors.forename: J J
authors.initials: JJ
authors.lastname: Archelos
authors.forename: S
authors.initials: S
authors.lastname: Jung
authors.forename: H
authors.initials: H
authors.lastname: Stodal
authors.forename: H
authors.initials: H
authors.lastname: Lassmann
authors.forename: K V
authors.initials: KV
authors.lastname: Toyka
authors.forename: A
authors.initials: A
authors.lastname: Haase
authors.forename: H P
authors.initials: HP
authors.lastname: Hartung
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001812:Blood-Brain Barrier; D003287:Contrast Media; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D005260:Female; D019786:Gadolinium DTPA; D007116:Immunization, Passive; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D008279:Magnetic Resonance Imaging; D009942:Organometallic Compounds; D004369:Pentetic Acid / Q000031:analogs & derivatives; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; D009942:Organometallic Compounds; D018799:Intercellular Adhesion Molecule-1; D004369:Pentetic Acid; D019786:Gadolinium DTPA