Oxidative stress (OS) is one of the most significant propagators of systemic damage with implications for widespread pathologies such as vascular disease, accelerated aging, degenerative disease, inflammation, and traumatic injury. OS can be induced by numerous factors such as environmental conditions, lifestyle choices, disease states, and genetic susceptibility. It is tied to the accumulation of free radicals, mitochondrial dysfunction, and insufficient antioxidant protection, which leads to cell aging and tissue degeneration over time. Unregulated systemic increase in reactive species, which contain harmful free radicals, can lead to diverse tissue-specific OS responses and disease. Studies of OS in the brain, for example, have demonstrated how this state contributes to neurodegeneration and altered neural plasticity. As the worldwide life expectancy has increased over the last few decades, the prevalence of OS-related diseases resulting from age-associated progressive tissue degeneration. Unfortunately, vital translational research studies designed to identify and target disease biomarkers in human patients have been impeded by many factors (e.g., limited access to human brain tissue for research purposes and poor translation of experimental models). In recent years, stem cell–derived three-dimensional tissue cultures known as “brain organoids” have taken the spotlight as a novel model for studying central nervous system (CNS) diseases. In this review, we discuss the potential of brain organoids to model the responses of human neural cells to OS, noting current and prospective limitations. Overall, brain organoids show promise as an innovative translational model to study CNS susceptibility to OS and elucidate the pathophysiology of the aging brain.

中文翻译：

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脑类器官：评估氧化应激诱导的中枢神经系统损伤的有前景的模型

氧化应激 (OS) 是全身性损伤最重要的传播因素之一，对血管疾病、加速衰老、退行性疾病、炎症和创伤性损伤等广泛的病理有影响。OS 可由多种因素诱发，例如环境条件、生活方式选择、疾病状态和遗传易感性。它与自由基的积累、线粒体功能障碍和抗氧化保护不足有关，随着时间的推移会导致细胞老化和组织退化。含有有害自由基的反应性物种不受调节的系统性增加可导致多种组织特异性 OS 反应和疾病。例如，对大脑中 OS 的研究已经证明了这种状态如何导致神经退行性变和改变神经可塑性。随着过去几十年全球预期寿命的增加，与年龄相关的进行性组织退化导致 OS 相关疾病的流行。不幸的是，旨在识别和靶向人类患者疾病生物标志物的重要转化研究受到许多因素的阻碍（例如，出于研究目的而对人类脑组织的访问有限以及实验模型的翻译不佳）。近年来，被称为“脑类器官”的干细胞衍生的三维组织培养物已成为研究中枢神经系统（CNS）疾病的新模型。在这篇综述中，我们讨论了大脑类器官在模拟人类神经细胞对 OS 的反应方面的潜力，并指出了当前和未来的局限性。全面的，