PDF(Pubmed)
Abstract：
Glutamate grabbers, such as glutamate oxaloacetate transaminase (GOT), have been proposed to prevent excitotoxicity secondary to high glutamate levels in stroke patients. However, the efficacy of blood glutamate grabbing by GOT could be dependent on the extent and severity of the disruption of the blood-brain barrier (BBB). Our purpose was to analyze the relationship between GOT and glutamate concentration with the patient\'s functional status differentially according to BBB serum markers (soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and leukoaraiosis based on neuroimaging). This retrospective observational study includes 906 ischemic stroke patients. We studied the presence of leukoaraiosis and the serum levels of glutamate, GOT, and sTWEAK in blood samples. Functional outcome was assessed using the modified Rankin Scale (mRS) at 3 months. A significant negative correlation between GOT and glutamate levels at admission was shown in those patients with sTWEAK levels > 2900 pg/mL (Pearson\'s correlation coefficient: -0.249; p < 0.0001). This correlation was also observed in patients with and without leukoaraiosis (Pearson\'s correlation coefficients: -0.299; p < 0.001 vs. -0.116; p = 0.024). The logistic regression model confirmed the association of higher levels of GOT with lower odds of poor outcome at 3 months when sTWEAK levels were >2900 pg/mL (OR: 0.41; CI 95%: 0.28-0.68; p < 0.0001) or with leukoaraiosis (OR: 0.75; CI 95%: 0.69-0.82; p < 0.0001). GOT levels are associated with glutamate levels and functional outcomes at 3 months, but only in those patients with leukoaraiosis and elevated sTWEAK levels. Consequently, therapies targeting glutamate grabbing might be more effective in patients with BBB dysfunction.
摘要：
谷氨酸抓取者，如谷氨酸草酰乙酸转氨酶（GOT），已提出预防中风患者高谷氨酸水平继发的兴奋性毒性。然而,GOT捕获血谷氨酸的功效可能取决于血脑屏障(BBB)破坏的程度和严重程度.我们的目的是根据BBB血清标志物（基于神经影像学的可溶性肿瘤坏死因子样弱凋亡诱导剂（sTWEAK）和脑白质疏松），分析GOT和谷氨酸浓度与患者功能状态的关系。这项回顾性观察研究包括906名缺血性卒中患者。我们研究了脑白质疏松症的存在和血清谷氨酸水平，有,和血液样本中的sTWEAK。在3个月时使用改良的Rankin量表（mRS）评估功能结果。在sTWEAK水平>2900pg/mL的患者中，GOT和谷氨酸水平之间呈显著负相关（Pearson相关系数：-0.249；p<0.0001）。在患有和不患有脑白质疏松症的患者中也观察到了这种相关性（Pearson相关系数：-0.299；p<0.001vs.-0.116；p=0.024）。逻辑回归模型证实，当sTWEAK水平>2900pg/mL（OR：0.41；CI95％：0.28-0.68；p<0.0001）或与脑白质疏松（OR：0.75；CI95％：0.69-0.82；p<0.0001）时，在3个月时，较高的GOT水平与较低的不良预后相关。GOT水平与3个月时的谷氨酸水平和功能结果相关，但仅限于患有脑白质疏松和sTWEAK水平升高的患者。因此,针对谷氨酸捕获的治疗可能对BBB功能障碍患者更有效.
