Activation of the Kynurenine Pathway in the Acute Phase of Stroke and its Role in Fatigue and Depression Following Stroke
Activation of the Kynurenine Pathway in the Acute Phase of Stroke and its Role in Fatigue and Depression Following Stroke
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DOI：
10.1007/s12031-014-0272-0
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发表时间：
2014-10-01
影响因子：
3.1
通讯作者：
Sandvik, Leiv
中科院分区：
文献类型：
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作者：
Ormstad, Heidi;Verkerk, Robert;Sandvik, Leiv
许多中风幸存者遭受中风后疲劳（PSF）和中风后抑郁症（PSD），这表明增加对这些后遗症的机制的知识基础的重要性。本研究的主要目的是确定犬尿氨酸（KYN）通路的激活是否可预测急性缺血性卒中（AIS）患者随后的疲劳或抑郁。急性血清5-羟色胺（5-HT），色氨酸（TRP）催化剂（TRYCATs），竞争氨基酸，以及随后的疲劳和抑郁症，在45例中风患者进行了测量。TRP指数[=100 x TRP /（酪氨酸+缬氨酸+苯丙氨酸+亮氨酸+异亮氨酸）]在12个月时疲劳严重程度量表（FSS）评分为千分之一日元4的患者中显著低于FSS评分< 4的患者（p = 0.039）。此外，在18个月时，FSS评分为千分之一日元4的患者在急性卒中期的血清犬尿烯酸水平显著高于FSS评分< 4的患者（p = 0.026）。这些结果表明，PSF的脑卒中患者在急性脑卒中阶段具有较低的TRP用于脑内5-HT合成的生物利用度。然而，它们在该阶段似乎也具有更大的神经保护潜力。与PSF相比，没有发现PSD的预测因子，这些结果与以前的研究结果一起表明，AIS后的免疫反应和吲哚胺2，3-双加氧酶激活可以预测PSF，但不能预测PSD。
Many stroke survivors suffer from poststroke fatigue (PSF) and poststroke depression (PSD), indicating the importance of increasing the base of knowledge about the mechanisms underlying these sequelae. The primary aim of this study was to determine whether activation of the kynurenine (KYN) pathway predicts subsequent fatigue or depression in acute ischemic stroke (AIS) patients. Acute serum levels of 5-hydroxytryptamine (5-HT), tryptophan (TRP) catabolites (TRYCATs), and competing amino acids, as well as subsequent fatigue and depression, were measured in 45 stroke patients. TRP index [=100 x TRP / (tyrosine + valine + phenylalanine + leucine + isoleucine)] was significantly lower in patients with a Fatigue Severity Scale (FSS) score of a parts per thousand yen4 at 12 months than in those with an FSS score of < 4 (p = 0.039). Furthermore, the serum level of kynurenic acid in the acute stroke phase was significantly higher in patients with an FSS of score a parts per thousand yen4 at 18 months than in those with an FSS score of < 4 (p = 0.026). These findings indicate that stroke patients with PSF have a lower bioavailability of TRP for 5-HT synthesis in the brain in the acute stroke phase. However, they also appear to have greater neuroprotective potential in that phase. In contrast to PSF, no predictors of PSD were found. These findings together with those of previous studies suggest that the immune response and indoleamine 2,3-dioxygenase activation that follows AIS can predict PSF but not PSD.