Abstract
The acknowledgement of risks for traumatic brain injury in American football players has prompted studies for sideline concussion diagnosis and testing for neurological deficits. While concussions are recognized etiological factors for a spectrum of neurological sequelae, the consequences of sub-concussive events are unclear. We tested the hypothesis that blood-brain barrier disruption (BBBD) and the accompanying surge of the astrocytic protein S100B in blood may cause an immune response associated with production of auto-antibodies. We also wished to determine whether these events result in disrupted white matter on diffusion tensor imaging (DT) scans. Players from three college football teams were enrolled (total of 67 volunteers). None of the players experienced a concussion. Blood samples were collected before and after games (n = 57); the number of head hits in all players was monitored by movie review and post-game interviews. S100B serum levels and auto-antibodies against S100B were measured and correlated by direct and reverse immunoassays (n = 15 players; 5 games). A subset of players underwent DTI scans pre- and post-season and after a 6-month interval (n = 10). Cognitive and functional assessments were also performed. After a game, transient BBB damage measured by serum S100B was detected only in players experiencing the greatest number of sub-concussive head hits. Elevated levels of auto-antibodies against S100B were elevated only after repeated sub-concussive events characterized by BBBD. Serum levels of S100B auto-antibodies also predicted persistence of MRI-DTI abnormalities which in turn correlated with cognitive changes. Even in the absence of concussion, football players may experience repeated BBBD and serum surges of the potential auto-antigen S100B. The correlation of serum S100B, auto-antibodies and DTI changes support a link between repeated BBBD and future risk for cognitive changes.
Highlights
A recent review of the current practice of concussion management and time until return to play in the National Football League over a 5 year period from 1996–2001 showed that 50% of players returned to the same game after sustaining a concussion
The demographic characteristics of the subjects enrolled in this study are shown in Figure 1 and Table 1 where the correlation between S100B levels, race, age, body mass index (BMI), history of previous concussion and field positions are reported
In this study we have shown that elevations of serum S100B indicating blood-brain barrier disruption occur in football players who experience sub-concussive head hits (SHH) below the threshold for a diagnosis of concussion
Summary
A recent review of the current practice of concussion management and time until return to play in the National Football League over a 5 year period from 1996–2001 showed that 50% of players returned to the same game after sustaining a concussion. Concussions can produce symptoms that are of short or long duration lasting from several minutes to several months. Severe post-concussive symptoms have been reported to last several years in some athletes and have caused numerous athletes to retire from sports altogether. Short-term outcomes include cognitive defects, but in some cases there is evidence of permanent or subtle neurologic decline even after just one injury. Blood-brain barrier disruption (BBBD) or increased permeability of the brain vasculature has been linked to a variety of neurological disorders including seizures, Alzheimer’s disease, stroke, and traumatic brain injury [3]. BBB failure can be pathogenic acutely or after a delay lasting anywhere from hours to years [4,5,6]. Circulating autoantibodies against CNS antigen become pathogenic to the brain when the BBB allows their access into the brain [10]
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