Serum neurofilament light chain, inflammatory markers, and kynurenine metabolites in patients with persistent post-concussion symptoms: A cohort study

Background: Concussion leads to persistent post-concussion symptoms (PPCS) in up to one-third of those affected. While previous research has linked the initial trauma to elevated serum levels of neurofilament light chain (NFL), inflammatory markers, and neurotoxic metabolites within the kynurenine pathway, few studies have explored their relevance in PPCS. This study aims to investigate these biomarkers in PPCS patients, elucidating their relevance in the prolonged phase of concussion. Methods: Serum samples from 86 PPCS individuals aged 18-30 years, 2-6 months post-trauma were analyzed, with 54 providing follow-up samples after seven months. NFL was measured using single-molecule array (Simoa) technology, 13 inflammatory markers via a Luminex immunoassay, and five kynurenine metabolites using liquid chromatography-mass spectrometry. A control group of 120 healthy anonymous blood donors was recruited for comparison. Results: No significant NFL differences were found in PPCS participants compared with healthy individuals (p = 0.22). Intriguingly, a subset (9.3%) of PPCS participants initially exhibited abnormally high NFL levels (>9.7 pg/mL), which normalized upon follow-up (p = 0.032). Additionally, serum levels of the inflammatory markers, monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1/CCL11 were 25-40% lower than in healthy individuals (p <= 0.001). As hypothesized, PPCS participants exhibited a 22% reduction in the ratio of kynurenic acid to quinolinic acid (neuroprotective index) (p < 0.0001), indicating a shift towards the formation of neurotoxic metabolites. Conclusion: NFL may serve as a biomarker to monitor recovery, and future studies should investigate the potential therapeutic benefits of modulating the kynurenine pathway to improve PPCS.