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Neurofilament Light Chain (Nfl) Level in Serum as a Suitable In Vivo Biomaker for Axonal Damage in a Murine Viral Model of Multiple Sclerosis

A. Segna, R. Wannemacher, K. Rohn, V. Sippel, M. Steiner, F. Lühder, A. Flügel, W. Baumgärtner et al.

Journal of Cellular and Molecular Medicine, 2026

Abstract

Neurofilament light chain (Nfl) is a protein of the cytoskeleton predominantly found in large calibre myelinated axons and a suitable in vivo biomarker for monitoring neurodegenerative processes. Axonal damage results in Nfl release into the cerebrospinal fluid and the blood stream. Axonal damage is a frequent finding in Theiler's murine encephalomyelitis virus (TMEV)‐infected SJL mice, a viral model for multiple sclerosis. Following the hypothesis that TMEV‐associated axonal damage is reflected by serum Nfl (sNfl) levels, histopathological findings were compared with sNfl levels at 7, 14, 42 and 147/85 days post infection (dpi) in TMEV‐susceptible SJL and ‐resistant C57BL/6 mice. Axonal damage was evaluated by immunohistochemistry for β‐amyloid precursor protein (βAPP) and synaptophysin (syn). Both markers were significantly increased at 42 and 85 dpi in the spinal cord of SJL mice, whereas no axonopathy was observed in the spinal cord of C57BL/6 mice. Similarly, significantly increased sNfl values were only observed in SJL mice at 42 and 85 dpi but not in C57BL/6 mice. Results show a positive correlation between histochemically detected axonal damage and sNfl in TMEV‐infected SJL mice. Thus, sNfl represents a potential marker for in vivo monitoring of axonal damage in this animal model.

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