Neurofilament light concentrations in serum following experimental rotational traumatic brain injury in rats

Conference poster, 2017

The protein neurofilament light (NFL) is predominantly expressed in the long myelinated subcortical axons. Measurement of NFL in serum of athletes after head trauma have been shown to correlate with the severity of brain injury. However, experimental models that allow for studies of NFL in serum in combination with studies of structural brain injuries are limited. Therefore, the aim of this study was to measure NFL in serum from rats following experimental sagittal plane rotation trauma and to compare these measurements to data on accumulation of Amyloid Precursor Protein (APP) in the white matter following similar type and severity trauma. Spray Dawley rats (n=65) were exposed to rapid sagittal plane rotational acceleration head trauma (maximum rotational acceleration 1.40 ± 0.32 (mean ± SD, n=29). Serum samples were collected just prior to termination at 2.5, 24, 72, 120, 168 and 672 hours post trauma. The NFL serum concentration was studied using NFL immunoassay on the single molecule array (Simoa) platform. The trauma caused subdural bleedings in most animals. Staining brain tissue with APP antibodies and FD Neurosilver revealed wide spread axonal injuries in the corpus callosum, the border between the corpus callosum and cortex and in tracts in the brain stem. Only limited signs of contusion injuries were observed following trauma. Macrophage invasions, glial fibrillary acidic protein redistribution or hypertrophy, and blood brain barrier (BBB) changes were unusual. Traumatized animals exhibited increased NFL concentrations compared to sham exposed animals for all survival times; for survival times 24 h the increase was 8 times (exposed 666 pg/mL (range 327 to 1421 pg/mL) sham 83 pg/mL (range 40 to 114 pg/mL). The shorter and longer survival times resulted in lesser increase. At 2.5 hours and 28 days post trauma the NL serum concentration increase were approximately 2.5 times. The measured NFL leakage to the blood system appear to occur despite the absence of obvious BBB injuries. Serum NFL concentration appear to correlate with APP level in the white matter for all time points studied. In conclusion NFL serum concentrations in experimental trauma was more prominent than those reported following sports-related concussion and when using the same immunoassay technique. This study supports the hypothesis that mild rotational trauma is associated with acute axonal injury and serum NFL may offer diagnostic utility for such trauma. NFL serum level increased following trauma despite no apparent BBB injury.