Correlation between MRI and clinico-pathological manifestations in Lewis rats protected from experimental allergic encephalomyelitis by acylated synthetic peptide of myelin basic protein

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of t he central nervous system which constitutes an accepted animal model for mu ltiple sclerosis (MS), The disease can take an acute or chronic form depend ing on the injection route, animal strain and nature of the disease-inducin g antigen administered. The neuroinflammation associated with the acute for m can be detected with T-2-weighted, T-1-weighted and diffusion MRI, and bl ood-brain barrier changes can be investigated with Gd-DTPA-enhanced T-1-wei ghted imaging, similar to that of MS patients. A synthetic peptide of myeli n basic protein (MBP) encephalitogenic for the Lewis rat (MBP 68-86) was ac ylated by the attachment of a palmitoyl residue(PAL68-86), and was shown to confer almost complete protection against EAE, when administered to rats b efore and after an encephalitogenic challenge. In this study, treatment of Lewis rats with PAL68-86 prevented the appearance of clinical signs (p < 0. 0001) after challenge with the native peptide (p68-86) in complete Freund's adjuvant (CFA), and reduced considerably the MRI and histopathological sig ns of the disease (p < 0.0001). Measurement of the gadolinium leakage due t o neuroinflammation revealed a significant decrease in permeability from 4. 09 +/- 2.1 to 2.95 +/- 1.79% pixels > mean + 2 SD (p = 0.011). Therefore, q uantitative MRI measurements correlate very well with the reduced cellular infiltration in the CNS and the absence of clinical signs in the EAE-protec ted animal. (C) 1999 Elsevier Science Inc.