Chronic relapsing necrotizing encephalomyelitis produced by myelin basic protein in mice

Area of Science:

• Neuroimmunology
• Experimental models of autoimmune diseases

Background:

• Chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) is typically induced by whole white matter, not myelin basic protein (MBP).
• Existing models often exhibit purely demyelinative lesions, differing from human conditions like multiple sclerosis (MS).

Purpose of the Study:

• To describe a novel CR-EAE model in SJL mice induced by MBP.
• To characterize the pathological features and disease course of this new model.
• To compare this model with existing CR-EAE models and human MS.

Main Methods:

• Induction of CR-EAE in SJL mice using single inoculation of MBP in complete Freund's adjuvant.
• Administration of varying MBP doses (100-800 µg).
• Long-term observation (up to 19 months) and histopathological analysis of lesions.

Main Results:

• A chronic relapsing or progressive EAE model was established with a prolonged latent period.
• Higher MBP doses (400-800 µg) were more effective in inducing disease.
• Lesions showed widespread nerve fiber destruction, Wallerian degeneration, and some demyelination, with early infiltration of polymorphonuclear leukocytes and macrophages.

Conclusions:

• This MBP-induced CR-EAE model in SJL mice presents with significant destructive lesions, unlike purely demyelinative models.
• The pathological features, including nerve fiber destruction and inflammatory infiltrate, offer a distinct model for studying neuroinflammatory processes.
• This model may provide insights into aspects of EAE and human demyelinating diseases that are not captured by other models.