Research paper
Partial inhibition of AT-EAE by an antibody to ICAM-1: Clinico-histological and MRI studies

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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.

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