Prospective study of the effects of sport-related concussion on serum kynurenine pathway metabolites.
Prospective study of the effects of sport-related concussion on serum kynurenine pathway metabolites.
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运动相关脑震荡对血清犬尿氨酸途径代谢物影响的前瞻性研究。
DOI：
10.1016/j.bbi.2020.03.002
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Savitz,Jonathan
中科院分区：
文献类型：
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作者：
Meier,TimothyB;Nitta,MorganE;Teague,TKent;Nelson,LindsayD;McCrea,MichaelA;Savitz,Jonathan
前运动员神经退行性和精神疾病的报道增加了公众对运动相关脑震荡（SRC）急性和慢性影响的关注。SRC精神后遗症的个体差异背后的生物学因素及其在潜在长期负面结果中的作用尚未确定。已知的脑震荡炎症反应的一个未充分研究的生物学后果是激活一个关键的免疫调节途径，犬尿氨酸途径（KP）。KP的激活产生几种与精神和神经退行性疾病相关的神经活性代谢物。我们检验了SRC导致具有神经毒性的血清KP代谢物（喹啉酸[QuinA]， 3-羟基犬尿氨酸[3HK]）升高以及神经保护代谢物犬尿酸（KynA）降低的假设，并且这些代谢物可以预测脑震荡后的心理症状。此外，由于脑损伤被认为是启动免疫系统，第二个目标是验证一个假设，即与首次脑震荡的运动员相比，急性SRC和既往SRC病史的运动员的神经毒性相对于神经保护性KP代谢物会升高。高中和大学橄榄球运动员（N = 1136）参加了季前赛基线访问，包括临床测试和血液样本采集。患有SRC的运动员（N = 59）在受伤后6小时（急性早期）、24-48小时（急性晚期）以及8、15和45天完成了随访。未受伤的接触性运动（CC, N = 54）和非接触性运动运动员完成了类似的访问，并作为对照组（NCC, N = 30）。使用简短症状量表-18 （BSI）评估，SRC运动员在受伤后急性出现的心理症状明显高于对照组。血清中KynA/3HK的比值（一种神经保护指数）与随访组之间存在相互作用，SRC运动员急性期早期随访时KynA/3HK相对于后期随访时升高。重要的是，在急性早期就诊时这种神经保护指数较高的运动员在急性晚期就诊时报告的抑郁症状较少。最后，与没有脑震荡前科的SRC运动员相比，在所有访问中，有脑震荡前科的SRC运动员的血清KynA/QuinA显著降低，这一效应是由有脑震荡前科的SRC运动员的QuinA升高引起的。这些结果表明，早期急性激活KP的KynA分支可能防止脑震荡后抑郁症状的发展。此外，他们强调了血清QuinA作为重复性头部损伤生物标志物的潜力，并提供了将先前脑震荡与随后损伤联系起来的可能机制。
Reports of neurodegenerative and psychiatric disease in former athletes have increased public concern about the acute and chronic effects of sport-related concussions (SRC). The biological factors underlying individual differences in the psychiatric sequalae of SRC and their role in potential long-term negative outcomes have not been determined. One understudied biological consequence of the known inflammatory response to concussion is the activation of a key immunoregulatory pathway, the kynurenine pathway (KP). Activation of the KP produces several neuroactive metabolites that have been associated with psychiatric and neurodegenerative diseases. We tested the hypothesis that SRC results in an elevation of serum KP metabolites with neurotoxic properties (quinolinic acid [QuinA], 3-hydroxykynurenine [3HK]) together with a reduction in the neuroprotective metabolite kynurenic acid (KynA), and that these metabolites would predict post-concussion psychological symptoms. Additionally, because brain injury is thought to prime the immune system, a secondary goal was to test the hypothesis that athletes with acute SRC and a history of prior SRC would have elevated neurotoxic relative to neuroprotective KP metabolites compared to athletes that were concussed for the first time. High school and collegiate football players (N = 1136) were enrolled at a preseason baseline visit that included clinical testing and blood specimen collection. Athletes that suffered a SRC (N = 59) completed follow-up visits within 6-hours (early-acute), at 24–48 h (late-acute) and at 8, 15, and 45 days post-injury. Uninjured contact sport (CC; N = 54) and non-contact sport athletes completed similar visits and served as controls (NCC; N = 30). SRC athletes had significantly elevated psychological symptoms, assessed using the Brief Symptom Inventory-18 (BSI), acutely following injury relative to both control groups. There was a group-by-visit interaction on the ratio of KynA to 3HK in serum, a neuroprotective index, with elevated KynA/3HK in athletes with SRC at the early-acute visit relative to later visits. Importantly, athletes with greater elevation in this neuroprotective index at the early-acute visit reported fewer depressive symptoms at the late-acute visit. Finally, SRC athletes with prior concussion had significantly lower serum KynA/QuinA at all visits compared to SRC athletes with no prior concussion, an effect driven by elevated QuinA in SRC athletes with prior concussion. These results suggest that early-acute activation of the KynA branch of the KP may protect against the development of depressive symptoms following concussion. Furthermore, they highlight the potential of serum QuinA as a biomarker for repetitive head injury and provide insight into possible mechanisms linking prior concussion with subsequent injury.