Research Reports - Consequences of repeated blood-brain barrier disruption in football players

PLoS One. 2013;8(3):e56805

Marchi N, Bazarian JJ, Puvenna V, Janigro M, Ghosh C, Zhong J, Zhu T, Blackman E, Stewart D, Ellis J, Butler R, Janigro D

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.

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