INTRODUCTION Ischemic stroke (IS) is a major contributor to the global disease burden, and effective biomarkers for IS management in clinical practice are urgently needed. Metabolomics can detect metabolites that are small enough to cross the blood-brain barrier in a high-throughput manner, and thus represents a powerful tool for discovering biomarkers of IS. OBJECTIVES In this study, we conducted a systematic review to identify potential metabolic biomarkers and pathways that might facilitate risk predictions, clinical diagnoses, the recognition of complications, predictions of recurrence and an understanding of the pathogenesis of IS. METHODS The PubMed and Web of Science databases were searched for relevant studies published between January 2000 and July 2019. The study objectives, study designs and reported metabolic biomarkers were systematically examined and compared. Pathway analysis was performed using the MetaboAnalyst online software. RESULTS Twenty-eight studies were included in this systematic review. Many consistent metabolites, including isoleucine, leucine, valine, glycine, lysine, glutamate, LysoPC(16:0), LysoPC(18:2), serine, uric acid, citrate and palmitic acid, possess potential as biomarkers of IS. Metabolic pathways and dysregulations that are implicated in excitotoxicity, inflammation, apoptosis, oxidative stress, neuroprotection, energy failure, and elevation of intracellular Ca2+ levels, were indicated as playing important roles in the development and progression of IS. CONCLUSIONS This systematic review summarizes potential metabolic biomarkers and pathways related to IS, which may provide opportunities for the construction of diagnostic or predictive models for IS and the discovery of novel therapeutic targets.

中文翻译：

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代谢组学促进了缺血性中风的代谢生物标志物和途径的发现：系统综述。

简介缺血性中风（IS）是造成全球疾病负担的主要因素，因此迫切需要在临床实践中对IS管理进行有效的生物标记。代谢组学可以检测足够小的代谢物，以高通量的方式穿过血脑屏障，因此它是发现IS的生物标记物的有力工具。目的在这项研究中，我们进行了系统的综述，以鉴定可能有助于风险预测，临床诊断，并发症识别，复发预测以及对IS发病机理的理解的潜在代谢生物标记物和途径。方法检索PubMed和Web of Science数据库，以查找2000年1月至2019年7月之间发表的相关研究。研究设计和报告的代谢生物标志物得到系统地检查和比较。使用MetaboAnalyst在线软件进行路径分析。结果本系统评价包括28项研究。许多一致的代谢物，包括异亮氨酸，亮氨酸，缬氨酸，甘氨酸，赖氨酸，谷氨酸，LysoPC（16：0），LysoPC（18：2），丝氨酸，尿酸，柠檬酸和棕榈酸，具有作为IS的生物标记物的潜力。代谢途径和失调与兴奋性毒性，炎症，细胞凋亡，氧化应激，神经保护，能量衰竭和细胞内Ca2 +水平升高有关，被认为在IS的发生和发展中起着重要作用。结论本系统评价总结了与IS相关的潜在代谢生物标志物和途径，