Brain stroke (BS, also known as a cerebrovascular accident), represents a serious global health crisis. It has been a leading cause of permanent disability and unfortunately, frequent fatalities due to lack of timely medical intervention. While progress has been made in prevention and management, the complexities and consequences of stroke continue to pose significant challenges, especially, its impact on patient’s quality of life and independence. During stroke, there is a substantial decrease in oxygen supply to the brain leading to alteration of cellular metabolic pathways, including those involved in mitochondrial-damage, leading to mitochondrial-dysfunction. The present proof-of-the-concept metabolomics study has been performed to gain insights into the metabolic pathways altered following a brain stroke and discover new potential targets for timely interventions to mitigate the effects of cellular and mitochondrial damage in BS. The serum metabolic profiles of 108 BS-patients were measured using 800 MHz NMR spectroscopy and compared with 60 age and sex matched normal control (NC) subjects. Compared to NC, the serum levels of glutamate, TCA-cycle intermediates (such as citrate, succinate, etc.), and membrane metabolites (betaine, choline, etc.) were found to be decreased BS patients, whereas those of methionine, mannose, mannitol, phenylalanine, urea, creatine and organic acids (such as 3-hydroxybutyrate and acetone) were found to be elevated in BS patients. These metabolic changes hinted towards hypoxia mediated mitochondrial dysfunction in BS-patients. Further, the area under receiver operating characteristic curve (ROC) values for five metabolic features (methionine, mannitol, phenylalanine, mannose and urea) found to be more than 0.9 suggesting their high sensitivity and specificity for differentiating BS from NC subjects.

Graphical abstract

中文翻译：

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基于核磁共振的血清代谢组学揭示了与脑中风氧化应激和线粒体损伤相关的代谢特征

脑中风（BS，也称为脑血管意外）代表着严重的全球健康危机。它是造成永久性残疾的主要原因，不幸的是，由于缺乏及时的医疗干预，经常导致死亡。尽管在预防和管理方面取得了进展，但中风的复杂性和后果仍然构成重大挑战，特别是它对患者生活质量和独立性的影响。中风期间，大脑的供氧量大幅减少，导致细胞代谢途径发生改变，包括那些涉及线粒体损伤的途径，从而导致线粒体功能障碍。目前的概念验证代谢组学研究旨在深入了解脑中风后代谢途径的改变，并发现及时干预的新潜在目标，以减轻脑卒中细胞和线粒体损伤的影响。使用 800 MHz NMR 波谱测量 108 名 BS 患者的血清代谢特征，并与 60 名年龄和性别匹配的正常对照 (NC) 受试者进行比较。与NC相比，BS患者血清谷氨酸、TCA循环中间体（如柠檬酸、琥珀酸等）和膜代谢物（甜菜碱、胆碱等）水平降低，而蛋氨酸、甘露糖水平降低。 、甘露醇、苯丙氨酸、尿素、肌酸和有机酸（如 3-羟基丁酸和丙酮）在 BS 患者中被发现升高。这些代谢变化暗示 BS 患者存在缺氧介导的线粒体功能障碍。此外，五种代谢特征（蛋氨酸、甘露醇、苯丙氨酸、甘露糖和尿素）的受试者工作特征曲线下面积 (ROC) 值超过 0.9，表明它们对于区分 BS 和 NC 受试者具有高敏感性和特异性。

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