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Positive association between serum quinolinic acid and functional connectivity following concussion
Brain, Behavior, and Immunity ( IF 15.1 ) Pub Date : 2021-01-01 , DOI: 10.1016/j.bbi.2020.11.011
Timothy B Meier 1 , Lezlie España 2 , Morgan E Nitta 3 , T Kent Teague 4 , Benjamin L Brett 5 , Lindsay D Nelson 5 , Michael A McCrea 5 , Jonathan Savitz 6
Affiliation  

The molecular mechanisms underlying the diverse psychiatric and neuropathological sequalae documented in subsets of athletes with concussion have not been identified. We have previously reported elevated quinolinic acid (QuinA), a neurotoxic kynurenine pathway metabolite, acutely following concussion in football players with prior concussion. Similarly, work from our group and others has shown that increased functional connectivity strength, assessed using resting state fMRI, occurs following concussion and is associated with worse concussion-related symptoms and outcome. Moreover, other work has shown that repetitive concussion may have cumulative effects on functional connectivity and is a risk factor for adverse outcomes. Understanding the molecular mechanisms underlying these cumulative effects may ultimately be important for therapeutic interventions or the development of prognostic biomarkers. Thus, in this work, we tested the hypothesis that the relationship between QuinA in serum and functional connectivity following concussion would depend on the presence of a prior concussion. Concussed football players with prior concussion (N=21) and without prior concussion (N=16) completed a MRI session and provided a blood sample at approximately 1 days, 8 days, 15 days, and 45 days post-injury. Matched, uninjured football players with (N=18) and without prior concussion (N=24) completed similar visits. The association between QuinA and global connectivity strength differed based on group (F(3, 127)=3.46, p=0.019); post-hoc analyses showed a positive association between QuinA and connectivity strength in concussed athletes with prior concussion (B=16.05, SE = 5.06, p=0.002, 95%CI[6.06, 26.03]), but no relationship in concussed athletes without prior concussion or controls. Region-specific analyses showed that this association was strongest in bilateral orbitofrontal cortices, insulae, and basal ganglia. Finally, exploratory analyses found elevated global connectivity strength in concussed athletes with prior concussion who reported depressive symptoms at the 1-day visit compared to those who did not report depressive symptoms (t(15)=2.37, mean difference=13.50, SE=5.69, p=0.032, 95%CI[1.36, 25.63], Cohen's d =1.15.). The results highlight a potential role of kynurenine pathway (KP) metabolites in altered functional connectivity following concussion and raise the possibility that repeated concussion has a "priming" effect on KP metabolism.

中文翻译:

脑震荡后血清喹啉酸与功能连接之间的正相关

脑震荡运动员亚群中记录的各种精神和神经病理学后遗症的分子机制尚未确定。我们之前曾报道过,在患有脑震荡的足球运动员脑震荡后,喹啉酸 (QuinA)(一种神经毒性犬尿氨酸途径代谢物)会急剧升高。同样,我们小组和其他人的工作表明,使用静息状态 fMRI 评估的功能连接强度增加,发生在脑震荡后,并且与更严重的脑震荡相关症状和结果相关。此外,其他工作表明,重复性脑震荡可能会对功能连接产生累积影响,并且是不良结果的风险因素。了解这些累积效应背后的分子机制可能最终对治疗干预或预后生物标志物的开发很重要。因此,在这项工作中,我们检验了以下假设:血清中的 QuinA 与脑震荡后的功能连接之间的关系取决于先前脑震荡的存在。先前有脑震荡 (N=21) 和无脑震荡 (N=16) 的脑震荡足球运动员完成了 MRI 会话,并在受伤后大约 1 天、8 天、15 天和 45 天提供了血液样本。有(N = 18)和没有脑震荡(N = 24)的匹配的、未受伤的足球运动员完成了类似的访问。QuinA 与全局连接强度之间的关联因组而异(F(3, 127)=3.46, p=0.019);事后分析显示,QuinA 与既往脑震荡的运动员的连接强度呈正相关(B=16.05,SE = 5.06,p=0.002,95%CI[6.06, 26.03]),但在没有脑震荡的运动员中没有相关性脑震荡或控制。特定区域的分析表明,这种关联在双侧眶额皮质、岛叶和基底神经节中最强。最后,探索性分析发现,与未报告抑郁症状的运动员相比,在 1 天就诊时报告有抑郁症状的有脑震荡史的脑震荡运动员的整体连接强度升高(t(15)=2.37,平均差=13.50,SE=5.69 , p=0.032, 95% CI[1.36, 25.63], Cohen's d =1.15.)。
更新日期:2021-01-01
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