Shahim Pashtun, Tegner Yelverton, Marklund Niklas, Höglund Kina, Portelius Erik, Brody David L, Blennow Kaj, Zetterberg Henrik
From the Institute of Neuroscience and Physiology (P.S., K.H., E.P., K.B., H.Z.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., K.H., E.P., K.B., H.Z.), Sahlgrenska University Hospital, Mölndal; Division of Medical Sciences, Department of Health Sciences (Y.T.), Luleå University of Technology; Department of Neuroscience, Neurosurgery (N.M.), Uppsala University, Uppsala, Sweden; Washington University School of Medicine (D.L.B.), St. Louis, MO; and Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK.
Neurology. 2017 Apr 11;88(15):1400-1407. doi: 10.1212/WNL.0000000000003816. Epub 2017 Mar 10.
To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood-brain barrier (BBB) impairment.
A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25-12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (Aβ38, Aβ40, Aβ42, sAPPα, and sAPPβ), and BBB function (CSF:serum albumin ratio).
Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS >1 year. Athletes with PCS >1 year had higher RPQ scores and number of concussions than athletes with PCS <1 year. Median concentrations of GFAP and YKL-40 were higher in athletes with PCS >1 year compared with controls, although with an overlap between the groups. YKL-40 correlated with RPQ score and the lifetime number of concussions. Athletes with rcTBI had lower concentrations of Aβ40 and Aβ42 than controls. The CSF:serum albumin ratio was unaltered.
This study suggests that PCS may be associated with biomarker evidence of astroglial activation and β-amyloid (Aβ) dysmetabolism in the brain. There was no clear evidence of Aβ deposition as Aβ40 and Aβ42 were reduced in parallel. The CSF:serum albumin ratio was unaltered, suggesting that the BBB is largely intact in PCS.
确定重复性震荡性创伤性脑损伤（rcTBI）所致的脑震荡后综合征（PCS）是否与星形胶质细胞活化、淀粉样蛋白沉积及血脑屏障（BBB）损伤的脑脊液生物标志物证据相关。
对47名参与者（28名患有PCS的职业运动员和19名对照者）进行了腰椎穿刺（末次脑震荡后中位时间1.5年，范围0.25 - 12年）、标准脑部MRI及Rivermead脑震荡后症状问卷（RPQ）评估。主要结局指标为脑脊液中星形胶质细胞活化标志物（胶质纤维酸性蛋白[GFAP]和YKL - 40）、反映淀粉样前体蛋白代谢的标志物（Aβ38、Aβ40、Aβ42、可溶性淀粉样前体蛋白α[sAPPα]和可溶性淀粉样前体蛋白β[sAPPβ]）以及血脑屏障功能（脑脊液：血清白蛋白比值）的浓度。
28名运动员中有9名在1年内恢复比赛，而19名患有持续时间>1年的PCS。PCS持续时间>1年的运动员比PCS持续时间<1年的运动员RPQ评分更高且脑震荡次数更多。PCS持续时间>1年的运动员中GFAP和YKL - 40的中位浓度高于对照者，尽管两组之间有重叠。YKL - 40与RPQ评分及终生脑震荡次数相关。rcTBI运动员的Aβ40和Aβ42浓度低于对照者。脑脊液：血清白蛋白比值未改变。
本研究提示，PCS可能与脑内星形胶质细胞活化及β - 淀粉样蛋白（Aβ）代谢异常的生物标志物证据相关。由于Aβ40和Aβ42同时降低，没有明确的Aβ沉积证据。脑脊液：血清白蛋白比值未改变，提示PCS患者血脑屏障基本完整。
