Department of Physiology, Ajou University School of Medicine, Suwon 16499, Korea.
College of Pharmacy, Sunchon National University, Suncheon 57922, Korea.
Cells. 2020 Jul 7;9(7):1630. doi: 10.3390/cells9071630.
Cerebral ischemia is caused by perturbations in blood flow to the brain that trigger sequential and complex metabolic and cellular pathologies. This leads to brain tissue damage, including neuronal cell death and cerebral infarction, manifesting clinically as ischemic stroke, which is the cause of considerable morbidity and mortality worldwide. To analyze the underlying biological mechanisms and identify potential biomarkers of ischemic stroke, various in vitro and in vivo experimental models have been established investigating different molecular aspects, such as genes, microRNAs, and proteins. Yet, the metabolic and cellular pathologies of ischemic brain injury remain not fully elucidated, and the relationships among various pathological mechanisms are difficult to establish due to the heterogeneity and complexity of the disease. Metabolome-based techniques can provide clues about the cellular pathologic status of a condition as metabolic disturbances can represent an endpoint in biological phenomena. A number of investigations have analyzed metabolic changes in samples from cerebral ischemia patients and from various in vivo and in vitro models. We previously analyzed levels of amino acids and organic acids, as well as polyamine distribution in an in vivo rat model, and identified relationships between metabolic changes and cellular functions through bioinformatics tools. This review focuses on the metabolic and cellular changes in cerebral ischemia that offer a deeper understanding of the pathology underlying ischemic strokes and contribute to the development of new diagnostic and therapeutic approaches.
脑缺血是由血流向大脑的波动引起的,继而引发一系列复杂的代谢和细胞病理。这导致脑组织损伤,包括神经元细胞死亡和脑梗死,临床上表现为缺血性脑卒中,这是全球发病率和死亡率较高的原因。为了分析潜在的生物学机制和确定缺血性脑卒中的潜在生物标志物,已经建立了各种体外和体内实验模型,研究了不同的分子方面,如基因、microRNAs 和蛋白质。然而,缺血性脑损伤的代谢和细胞病理仍未完全阐明,由于疾病的异质性和复杂性,各种病理机制之间的关系难以建立。基于代谢组学的技术可以提供关于疾病细胞病理状态的线索,因为代谢紊乱可能代表生物现象的终点。许多研究已经分析了来自脑缺血患者和各种体内和体外模型的样本中的代谢变化。我们之前分析了在体大鼠模型中氨基酸和有机酸以及多胺分布的水平,并通过生物信息学工具确定了代谢变化与细胞功能之间的关系。这篇综述重点介绍了脑缺血中的代谢和细胞变化,这些变化深入了解了缺血性脑卒中的病理学,并为新的诊断和治疗方法的发展做出了贡献。