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

Abstract

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system which constitutes an accepted animal model for multiple sclerosis (MS). The disease can take an acute or chronic form depending on the injection route, animal strain and nature of the disease-inducing antigen administered. The neuroinflammation associated with the acute form can be detected with T 2-weighted, T 1-weighted and diffusion MRI, and blood–brain barrier changes can be investigated with Gd-DTPA-enhanced T 1-weighted imaging, similar to that of MS patients. A synthetic peptide of myelin basic protein (MBP) encephalitogenic for the Lewis rat (MBP 68–86) was acylated by the attachment of a palmitoyl residue (PAL68–86), and was shown to confer almost complete protection against EAE, when administered to rats before 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 signs of the disease ( p < 0.0001). Measurement of the gadolinium leakage due to 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, quantitative MRI measurements correlate very well with the reduced cellular infiltration in the CNS and the absence of clinical signs in the EAE-protected animal.