Plasma Neurofilament Light and Glial Fibrillary Acidic Protein Levels over Thirty Days in a Porcine Model of Traumatic Brain Injury

• DOI: 10.1089/neu.2022.0070
• Publication Date: 2022-04-04T07:02:52Z
• Authors: Samuel S. Shin; Marco M. Hefti; Vanessa M. Mazandi; David A. Issadore; David F. Meaney; Andrea L. C. Schn...; Ramon Diaz-Arrastia; Todd J. Kilbaugh
• Keywords: 03 medical and health sciences; Diffusion Tensor Imaging; 0302 clinical medicine; Swine; Brain Injuries, Traumatic; Glial Fibrillary Acidic Protein; Intermediate Filaments; Animals; Biomarkers

To establish the clinical relevance of porcine model of traumatic brain injury (TBI) using the plasma biomarkers of injury with diffusion tensor imaging (DTI) over 30 days, we performed a randomized, blinded, pre-clinical trial using Yorkshire pigs weighing 7-10 kg. Twelve pigs were subjected to Sham injury (n = 5) by skin incision or TBI (n = 7) by controlled cortical impact. Blood samples were collected before the injury, then at approximately 5-day intervals until 30 days. Both groups also had DTI at 24 h and at 30 days after injury. Plasma samples were isolated and single molecule array (Simoa) was performed for glial fibrillary acidic protein (GFAP) and neurofilament light (NFL) levels. Afterwards, brain tissue samples were stained for β-APP. DTI showed fractional anisotropy (FA) decrease in the right corona radiata (ipsilateral to injury), contralateral corona radiata, and anterior corpus callosum at 1 day. At 30 days, ipsilateral corona radiata showed decreased FA. Pigs with TBI also had increase in GFAP and NFL at 1-5 days after injury. Significant difference between Sham and TBI animals continued up to 20 days. Linear regression showed significant negative correlation between ipsilateral corona radiata FA and both NFL and GFAP levels at 1 day. To further validate the degree of axonal injury found in DTI, β-APP immunohistochemistry was performed on a perilesional tissue as well as corona radiata bilaterally. Variable degree of staining was found in ipsilateral corona radiata. Porcine model of TBI replicates the acute increase in plasma biomarkers seen in clinical TBI. Further, long term white matter injury is confirmed in the areas such as the splenium and corona radiata. However, future study stratifying severe and mild TBI, as well as comparison with other subtypes of TBI such as diffuse axonal injury, may be warranted.