Validation of a novel biomarker for acute axonal injury in experimental autoimmune encephalomyelitis

Melissa M. Gresle, Gerry Shaw, Bevyn Jarrott, Estella N. Alexandrou, Anna Friedhuber, Trevor J. Kilpatrick, Helmut Butzkueven

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41 Citations (Scopus)

Abstract

In multiple sclerosis, inflammatory axonal injury is a key pathological mechanism responsible for the development of progressive neurological dysfunction. The injured axon represents a therapeutic target in this disease; however, therapeutic trials of neuroprotective candidates will initially require preclinical testing in an animal model of inflammatory axonal injury and subsequently the development of a reliable paraclinical measure of axonal degeneration in humans. In the present study, we demonstrate the validity of serum phosphorylated neurofilament H (pNF-H) as a marker of axonal injury in murine experimental autoimmune encephalomyelitis (EAE). At the time of maximum disease severity (EAE day 22), the average serum pNF-H level reached 5.7 ng/ml, correlating significantly with the EAE paraplegia score (r = 0.75, P < 0.001). On average, 40% of axons in the spinal cord were lost in EAE, and serum pNF-H levels were highly correlated with axon loss (r = 0.8, P < 0.001). Axonal injury was a severe and acute event, insofar as serum pNF-H levels were not significantly elevated at early (EAE day 12) or late (EAE days 35 and 50) disease time points. Our results demonstrate that acute inflammatory axonal injury is a pathological feature of murine MOG 35-55 EAE, indicating that this model may mirror the acute pathological events in active multiple sclerosis lesions. Furthermore, we have validated the serum pNF-H assay as an unbiased measurement of axonal injury in EAE, facilitating rapid screening of potential neuroprotective therapies in this model.

Original languageEnglish
Pages (from-to)3548-3555
Number of pages8
JournalJournal of Neuroscience Research
Volume86
Issue number16
DOIs
Publication statusPublished - 1 Dec 2008

Keywords

  • Axonal injury
  • Experimental autoimmune encephalomyelitis
  • Inflammation
  • Multiple sclerosis
  • Phosphorylated neurofilament heavy chain

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