Investigating the role of fibrinogen in inflammatory demyelination using combined high-resolution MRI and histopathology in the marmoset experimental autoimmune encephalomyelitis model

Authors

• NJ Lee
• SK Ha
• NJ Luciano
• EC Leibovitch
• J Lefeuvre
• MK Schindler
• P Sati
• K Akassoglou
• AC Silva
• S Jacobson
• DS Reich

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disorder that affects millions of patients worldwide. MS patients develop characteristic lesions in the central nervous system that have different pathological features depending on the stage of the lesion development. However, MS tissue is not routinely available for pathological analysis. Experimental autoimmune encephalomyelitis (EAE) in the common marmosets (Callithrix jacchus) recapitulates many radiological and pathological features of focal MS lesions in the white matter, rendering this model useful for studying MS pathophysiology. The marmoset model thus provides an opportunity to investigate how such lesions develop, as well as the relative timing of factors involved in their pathogenesis. We used high-resolution magnetic resonance imaging (MRI) to track marmoset EAE lesions in-vivo to determine their age, stages of development, and location. The lesions were further characterized using postmortem histopathological analyses targeting various markers, including fibrinogen. Fibrinogen is not only a marker for blood-brain barrier leakage, but also has been investigated for its pathogenic role in MS lesion development. Our data show that fibrinogen leaks from blood vessels in early, active lesions, and its pattern of distribution depends on lesion age. Lesions that are two weeks old or younger show patchy fibrinogen deposition around the lesion’s central vein, whereas fibrinogen is cleared from older lesions by phagocytes. In conclusion, our results show that fibrinogen is a reliable marker of the early, active stage of EAE lesion development.

Scientific Focus Area: Neuroscience

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