Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
J Pharmacol Sci. 2021 Jan;145(1):130-139. doi: 10.1016/j.jphs.2020.11.007. Epub 2020 Nov 21.
Cerebral ischemia/reperfusion injury activates microglia, resident immune cells in the brain, and allows the infiltration of circulating immune cells into the ischemic lesions. Microglia play both exacerbating and protective roles in pathological processes and are thus often referred to as "double-edged swords." In ischemic brains, blood-borne macrophages play a role that is distinct from that of resident activated microglia. Recently, the metabolic alteration of immune cells in the pathogenesis of inflammatory disorders including cerebral infarction has become a critical target for investigation. We begin this review by describing the multifaceted functions of microglia in cerebral infarction. Next, we focus on the metabolic alterations that occur in microglia during pathological processes. We also discuss morphological changes that take place in the mitochondria, leading to functional disturbances, accompanied by alterations in microglial function. Moreover, we describe the involvement of the reactive oxygen species that are produced during aberrant metabolic activity. Finally, we discuss therapeutic strategies to ameliorate aggravative changes in metabolism.
脑缺血/再灌注损伤激活小胶质细胞，即大脑中的常驻免疫细胞，并允许循环免疫细胞浸润到缺血性病变部位。小胶质细胞在病理过程中发挥着加剧和保护的双重作用，因此常被称为“双刃剑”。在缺血性大脑中，血源性巨噬细胞发挥的作用与常驻激活的小胶质细胞不同。最近，免疫细胞在包括脑梗死在内的炎症性疾病发病机制中的代谢改变已成为研究的关键靶点。我们首先通过描述小胶质细胞在脑梗死中的多种功能来展开这篇综述。接下来，我们重点介绍病理过程中小胶质细胞发生的代谢改变。我们还讨论了线粒体发生的形态变化，导致功能障碍，并伴有小胶质细胞功能的改变。此外，我们描述了异常代谢活动产生的活性氧的参与。最后，我们讨论了改善代谢恶化的治疗策略。
