Consequences of Repeated Blood-Brain Barrier Disruption in Football Players
Consequences of Repeated Blood-Brain Barrier Disruption in Football Players
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DOI：
10.1371/journal.pone.0056805
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发表时间：
2013-03-06
期刊：
影响因子：
3.7
通讯作者：
Janigro, Damir
中科院分区：
文献类型：
--
作者：
Marchi, Nicola;Bazarian, Jeffrey J.;Janigro, Damir
对美国橄榄球运动员创伤性脑损伤风险的认识促使了对场边脑震荡诊断和神经功能缺陷测试的研究。虽然脑震荡是公认的一系列神经系统后遗症的病因，但亚震荡事件的后果尚不清楚。我们测试了血脑屏障破坏（BBBD）和伴随的星形细胞蛋白S100B在血液中的激增可能导致与自身抗体产生相关的免疫反应的假设。我们还希望确定这些事件是否会导致扩散张量成像（DT）扫描时白质紊乱。来自三个大学橄榄球队的球员被招募（总共67名志愿者）。没有一个球员受到脑震荡。在比赛前后采集血样（n = 57）；所有球员的头部撞击次数都是通过电影评论和赛后采访来监测的。通过直接免疫和反向免疫测定测定S100B血清水平和自身抗S100B抗体，并进行相关性分析（n = 15名运动员，5场比赛）。一部分球员在赛季前和赛季后以及间隔6个月后接受了DTI扫描（n = 10）。还进行了认知和功能评估。比赛结束后，血清S100B测量的短暂性血脑屏障损伤仅在经历次震荡头部撞击次数最多的球员中检测到。仅在以BBBD为特征的反复次震荡事件后，抗S100B自身抗体水平升高。血清S100B自身抗体水平也预测MRI-DTI异常的持续存在，而MRI-DTI异常反过来又与认知变化相关。即使在没有脑震荡的情况下，足球运动员也可能经历反复的BBBD和血清中潜在自身抗原S100B的激增。血清S100B、自身抗体和DTI变化的相关性支持反复BBBD与未来认知变化风险之间的联系。
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 autoantigen S100B. The correlation of serum S100B, auto-antibodies and DTI changes support a link between repeated BBBD and future risk for cognitive changes.