NFL blood levels are moderated by subconcussive impacts in a cohort of college football players

Abstract

Repetitive subconcussive head impacts in contact/collision sports such as American football may contribute to long-term brain changes. However, the lack of data to measure the effects of repeated subconcussive blows limits our understanding of their potential contributions to neuropathological alterations including neuronal damage. Here we examined the impact of subconcussive head impacts as measured by an accelerometer embedded mouth guard on changes in blood levels of the neuronal protein neurofilament light (NFL) chain in 24 Division I college football players. Plasma levels of NFL as well as other biomarkers (e.g., plasma tau, S100β, near point of convergence) and clinical symptoms were assessed in this cohort at baseline and pre-post practices. The impact of frequency and linear and rotational head accelerations recorded via the mouth guard were examined in relation to NFL changes.Increases in NFL levels from baseline to post-practice were moderated by frequency and magnitude of head impacts (p=0.04). Players sustaining higher force and more frequent head impacts (n=17) showed significant increases in NFL levels from baseline to postpractice (p<0.001). However, there were no changes in NFL blood levels among players (n=7) sustaining lower force/less frequent head impacts (p=0.61). The greater number of hits and linear and rotational head accelerations were also associated with greater preto post-practice NFL level increases (p's<0.05). Greater pre-to post-practice increases in NFL were associated with greater pre-to post-practice increases in S100β (p<0.001), but not with total tau. Acute changes in NFL, similar to S100β, may be a clinically useful peripheral marker in tracking acute brain damage in collegiate football players.

Association Between Proteomic Blood Biomarkers and DTI/NODDI Metrics in Adolescent Football Players: A Pilot Study

“…Similar to tau protein, NfL functions as a scaffolding structural protein in axonal and dendritic branching and growth, and NfL undergoes post-translational modification by a series of phosphorylation events, which can make it vulnerable to mechanical stretch and shear stress (62). Growing evidence supports that NfL levels in blood have shown to reflect the progression of neurodegenerative condition (e.g., Alzheimer's disease, multiple sclerosis) ( [63][64][65], differentiate severities of TBI (66), predict clinical outcome (e.g., functional recovery, return-to-play) after severe TBI and concussion (67,68), and correlate with subconcussive head impact exposure (24,26,32,33). Unlike tau, however, we failed to observe significant correlations between NfL and diffusion metrics, which opposes the data by Ljungqvist et al (69) that showed an association between serum NfL and FA (R 2 = 0.83) 12 months after severe TBI.…”

Neurofilaments: The C-Reactive Protein of Neurology

“…Regardless of the type of contact sport, there seems to be a relationship between NF-L levels and the frequency and magnitude of the head impact [58,[61][62][63][64]151,152]. It is not yet clear, however, whether NF-L may serve as a biomarker for prediction of when it is safe to return to contact sports without the risk of permanent disability and chronic traumatic encephalopathy [153].…”

Sports-related concussions and subconcussive impacts in athletes: incidence, diagnosis, and the emerging role of EPA and DHA

“…This implies NF-L levels can be an effective tool at monitoring the severity of SCI accumulation in research settings going forward. A comprehensive study by Rubin et al (2019) compared NF-L with other biomarkers in division 1 football players and found a positive relationship between blood levels of NF-L and frequency of head impacts. Although this study and others use blood serum or plasma to measure NF-L rather than CSF, a strong correlation between the two has been noted (Kawata et al 2018b), further increasing the validity and reliability of NF-L.…”