title: Hyperphosphorylated neurofilament NF-H is a serum biomarker of axonal injury.
abstract: Several lines of reasoning suggest that the phosphorylated axonal form of the neurofilament subunit NF-H is likely to be released from damaged and diseased neurons in significant amounts. Detection of this protein in serum or CSF might therefore provide information about the presence and degree of neuronal loss. We therefore developed a sensitive NF-H ELISA capable of detecting picogram quantities of phosphorylated NF-H (pNF-H). This assay showed that soluble pNF-H immunoreactivity is readily detectable in the sera of adult rats following various types of experimental spinal cord injury (SCI) and traumatic brain injury (TBI), but is undetectable in the sera of normal animals. Here we describe details of the time course and extent of serum pNF-H expression following experimental SCI and TBI. Following SCI, serum pNF-H showed an initial peak of expression at 16h and a second, usually larger, peak at 3 days. Following TBI, lower levels of serum pNF-H were detected with a peak at 2 days post-injury. We also show that the higher levels of pNF-H released from injured spinal cord as compared to brain are in line with the approximately 20-fold higher levels of pNF-H present in spinal cord. These findings suggest that serum levels of pNF-H immunoreactivity may be used to conveniently monitor neuronal damage and degeneration in experimental and presumably clinical situations.
authors.affiliation: Department of Neuroscience, University of Florida College of Medicine, Gainesville, USA. shaw@mbi.ufl.edu
authors.forename: Gerry
authors.initials: G
authors.lastname: Shaw
authors.forename: Cui
authors.initials: C
authors.lastname: Yang
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ellis
authors.forename: Kevin
authors.initials: K
authors.lastname: Anderson
authors.forename: J
authors.initials: J
authors.lastname: Parker Mickle
authors.forename: Stephen
authors.initials: S
authors.lastname: Scheff
authors.forename: Brian
authors.initials: B
authors.lastname: Pike
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Anderson
authors.forename: Dena R
authors.initials: DR
authors.lastname: Howland
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016900:Neurofilament Proteins / Q000097:blood* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; C051774:neurofilament protein H