Partial inhibition of AT-EAE by an antibody to ICAM-1: clinico-histological and MRI studies.
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.
Morrissey
S P
SP
Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
Deichmann
R
R
Syha
J
J
Simonis
C
C
Zettl
U
U
Archelos
J J
JJ
Jung
S
S
Stodal
H
H
Lassmann
H
H
Toyka
K V
KV
Haase
A
A
Hartung
H P
HP
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
D000911:Antibodies, Monoclonal; D003287:Contrast Media; D009942:Organometallic Compounds; D018799:Intercellular Adhesion Molecule-1; D004369:Pentetic Acid; D019786:Gadolinium DTPA