Serum evaluation of NFL correlates with histological identification of degenerating axons

Abstract

Serum neurofilament light chain (NF-L) is a promising minimally invasive biomarker for axonal degeneration after neurological damage. The current work demonstrates the utility of serum NF-L as a biomarker for the extent of active axonal degeneration in the injured spinal cord. Adult Sprague Dawley rats received a unilateral C4 contusion (150kdyne). Brainstem and spinal cords were harvested, and serum was collected at 1 h, 6 h, 1 day, 3 days, or 10 days post-injury. Serum NF-L and glial fibrillary acid protein (GFAP) were assessed using the Quanterix® Simoa™ assay. Serial spinal cord cross-sections spanning the caudal medulla to the mid-thoracic spinal cord were stained with the NF-L Degenotag™ MCA-6H63 antibody, which specifically detects degenerating axonal profiles. Sections were qualitatively and quantitatively analyzed for the pattern and extent of axonal degeneration. MCA-6H63 staining and serum NF-L levels peaked at 1-3 days post SCI, and then declined. Further, serum NF-L and the number of MCA-6H63 positive axons were highly correlated across time points (R² = 0.739; p < 0.0001). These data support the hypothesis that serum NF-L levels are indicative of the amount of active axonal degeneration in the injured spinal cord and therefore provide a biomarker to monitor degeneration over time post injury.

Keywords: Axonal degeneration; Blood biomarkers; Serum neurofilament light chain; Spinal cord injury.