Significance of Ubiquitin Carboxy-Terminal Hydrolase L1 Elevations in Athletes after Sub-Concussive Head Hits

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.

Blood biomarkers for brain injury: What are we measuring?

“…While S100β is the most extensively studied TBI biomarker, how it reaches the peripheral circulation remains unclear. Despite the lack of consistent and direct mechanistic evidence, increased levels of S100β, which are typically viewed as a marker for activated astrocytes, are also regarded by many as a surrogate marker for diminished BBB integrity (Puvenna et al, 2014; Marchi et al, 2013; Kanner et al, 2003; Kapural et al, 2002). Since S100β does not cross an intact BBB, elevated serum levels of S100β following TBI have been attributed to BBB permeability.…”

Mind the gaps—advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions

“…[143][144][145] Serum levels of UCH-L1 may have diagnostic utility in concussion, 146 but recent evidence suggests a lack of correlation between elevated serum levels and subconcussive hits. 147 The clinical utility of UCH-L1 in paediatric populations warrants further study.…”

Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury

“…The mechanisms by which TBI contributes to permanent homeostatic changes within the central nervous system (CNS) remain poorly understood. Recent evidence implicates disruption of the blood brain barrier (BBB) as an important indicator of brain injury [3]. Blast TBI, in particular, contributes to a vascular pressure surge that challenges BBB integrity [4].…”