To explore changes in blood-based proteins related to neurodegeneration, neuroinflammation, and vascular dysfunction after traumatic brain injury to better understand the link between TBI and neuroinflammation.

Recent advances in highly multiplexed immunoassays have made feasible investigations into how neurodegenerative pathology relates to neuroinflammation and microvascular disease. TBI is an attractive model to understand the mechanisms of trauma-related neurodegeneration. We hypothesized that levels of proteins detectable in plasma differ between acute TBI and uninjured healthy controls (HC). 

Blood samples were collected from individuals with TBI at 1 day and 2 weeks post-injury from a single academic center. HC were friends of participants or community volunteers with a single sample collection. Plasma samples were analyzed using the Alamar NULISAseq^TM CNS120 panel. This panel measures 120 proteins associated with central nervous system diseases, including neurodegeneration, inflammation, and vascular disease. All data were normalized then log2 transformed prior to being analyzed through differential expression (DE) analysis with FDR adjusted p-values.

Plasma was obtained from 108 participants with TBI (mean[SD] age: 42.4[19.1], 79.6% male, median arrival Glasgow Coma Scale: 15 (IQR: 2)). 94 samples were assayed on the first or third day after injury, and 47 plasma samples were collected at 14 days after injury and analyzed. 25 HC (mean[SD] age: 32.7[12.0], 36% male) were sampled. At timepoint 1, TBI participants had 13 upregulated proteins, with serum amyloid A1 (SAA1), glial fibrillary acidic protein (GFAP), and interleukin-6 (IL-6) having the largest log fold changes compared to HC. 13 proteins were downregulated. At 2 weeks, only 3 proteins remained elevated compared to controls, with neurofilament light (NEFL) and neurofilament heavy (NEFH) having the highest fold changes.

This novel panel of CNS biomarkers suggests neuroinflammation-related biomarkers are prominently upregulated after TBI. Blood biomarkers show promise for identifying mechanistic endophenotypes of neurotrauma.