Abstract
The impact of sub-concussive head hits (sub-CHIs) has been recently investigated in American football players, a population at risk for varying degrees of post-traumatic sequelae. Results show how sub-CHIs in athletes translate in serum as the appearance of reporters of blood-brain barrier disruption (BBBD), how the number and severity of sub-CHIs correlate with elevations of putative markers of brain injury is unknown. Serum brain injury markers such as UCH-L1 depend on BBBD. We investigated the effects of sub-CHIs in collegiate football players on markers of BBBD, markers of cerebrospinal fluid leakage (serum beta 2-transferrin) and markers of brain damage. Emergency room patients admitted for a clinically-diagnosed mild traumatic brain injury (mTBI) were used as positive controls. Healthy volunteers were used as negative controls. Specifically this study was designed to determine the use of UCH-L1 as an aid in the diagnosis of sub-concussive head injury in athletes. The extent and intensity of head impacts and serum values of S100B, UCH-L1, and beta-2 transferrin were measured pre- and post-game from 15 college football players who did not experience a concussion after a game. S100B was elevated in players experiencing the most sub-CHIs; UCH-L1 levels were also elevated but did not correlate with S100B or sub-CHIs. Beta-2 transferrin levels remained unchanged. No correlation between UCH-L1 levels and mTBI were measured in patients. Low levels of S100B were able to rule out mTBI and high S100B levels correlated with TBI severity. UCH-L1 did not display any interpretable change in football players or in individuals with mild TBI. The significance of UCH-L1 changes in sub-concussions or mTBI needs to be further elucidated.
Highlights
Concussions are a frequent occurrence among contact sport athletes, estimates vary in the range of 1.6–3.8 million per year [1]
We used two different immunoassays for each marker and three distinct cohorts to study the behavior of serum markers after subconcussive head hits; these were football players, patients with a diagnosed traumatic brain injury and control subjects
We used S100B as a marker of blood-brain barrier integrity and the asialo form of transferrin as a marker of blood-toCSF barrier. The latter was, as expected, virtually unaffected by subconcussive events, while S100B levels, but not UCH-l1, directly correlated with subconcussive head hits and traumatic brain injury. These results are in sharp contrast with findings by others related to ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) [30], but confirm that S100B is a sensitive marker of subconcussive head hits and clinical mild traumatic brain injury (mTBI)
Summary
Concussions are a frequent occurrence among contact sport athletes, estimates vary in the range of 1.6–3.8 million per year [1]. The often neglected sub-concussive head blows (subCHIs) are even more common. Sub-CHIs occur frequently among athletes involved in football, soccer, and hockey [4,5,6]. The quest for peripheral markers of mTBI has been confounded by several factors, including the inconsistency in the definition of concussive or subconcussive head hits and the presence of a blood-brain barrier (BBB) separating the brain from the systemic circulation which is tapped to determine the presence or levels of brainderived signals [7,8]
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