Abstract presented at Society for Neuroscience Meeting, San Diego, October 2004.
Neurofilament subunit NF - H as a serum biomarker of spinal cord injury.
D.R.Howland1,2,4*; B.Pike2,4,6; R.Ellis1,2,4; J.P.Mickle2,3,4; D.K.Anderson1,2,3; G.Shaw2,4,5
1 Neurosci., 2 Neurosurgery, 3 McKnight Brain Inst., Malcom Randall VAMC, Gainesville, FL, USA, 4 Univ. of Florida, Gainesville, FL, USA; 5 EnCor Biotechnology Inc., Alachua, FL, USA; 6 OSR, NIH-NIGMS, Bethesda, MD, USA
Neurofilaments are the most abundant cytoskeletal components of neurons and are composed predominantly of three subunits, namely NF-L, NF-M and NF-H. In particular, NF-H has some unique properties that would render it sufficiently stable in the serum to be detectable with an appropriate antibody based assay. Therefore, we hypothesized that following spinal cord injury (SCI), NF-H, a major neuron-specific protein concentrated in axons, might be released from injured and dying neurons in amounts large enough to allow detection in serum. The detection of an appropriate neuron specific protein in serum would provide a convenient quantitative measure of the extent of neuronal damage and death in experimental and clinical contexts. In the current experiments, we examined NF-H levels in sera of rats subjected to SCI and compared them to the pre-operative sera of those same rats. Following low thoracic spinal cord hemisections, blood samples were taken at defined post-injury time points. NF-H was not detectable in the pre-operative samples. However, it was readily detected in sera within two hours following injury. The levels of NF-H continued to increase after two hours with an initial peak of expression at sixteen to twenty-four hours post-injury. A second, larger peak was seen at three-to-four days post-injury. Following this second peak, NF-H levels slowly decreased to near baseline levels during the second post-injury week. These findings show that NF-H can be readily detected in the sera of animals with CNS injuries and suggest that the measurement of serum levels of NF-H is a convenient method for assessing neuronal damage and death.