Espinoza-Rojo Mónica, Iturralde-Rodríguez Karen Ivonne, Chánez-Cárdenas María-Elena, Ruiz-Tachiquín Martha Eugenia, Aguilera Penélope
Laboratorio de Biología Molecular y Genómica, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México.
Cent Nerv Syst Agents Med Chem. 2010 Dec 1;10(4):317-25. doi: 10.2174/187152410793429755.
Ischemic stroke is a major cause of death worldwide that provokes a high society cost. Deprivation of blood supply, with the subsequent deficiency of glucose and oxygen, triggers an important number of mechanisms (e.g. excitotoxicity, oxidative stress and inflammation) leading to irreversible neuronal injury. Consequently, ischemia increases the energy demand which is associated with profound changes in brain energy metabolism. Glucose transport activity may adapt to ensure the delivery of glucose to maintain normal cellular function, even at the low glucose levels observed in plasma during ischemia. In the brain, the main glucose transporters (GLUTs) are GLUT3 in neurons and GLUT1 in the microvascular endothelial cells of the blood brain barrier and glia. The intracellular signaling pathways involved in GLUT regulation in cerebral ischemia remain unclear; however, it has been established that ischemia induces changes in their expression. In this review, we describe the effect of glutamate-induced excitotoxicity, mitochondrial damage, glucose deprivation, and hypoxia on GLUTs expression in the brain. Additionally, we discuss the possible role of GLUTs as therapeutic target for ischemia. Despite of the intense research, current therapeutics options for stroke are very limited, therefore it is especially important to find new options. Few studies have examined the neuroprotective potential of GLUT up-regulation in ischemic stroke; however, evidence suggests that augmented GLUTs could be related to a protective mechanism. Increased understanding of the beneficial effects of GLUTs activation provides the rationale for targeting GLUT in the development of new therapeutic strategies.
缺血性中风是全球主要的死亡原因，会引发高昂的社会成本。血液供应的剥夺，以及随之而来的葡萄糖和氧气缺乏，会触发大量机制（如兴奋性毒性、氧化应激和炎症），导致不可逆的神经元损伤。因此，缺血会增加能量需求，这与脑能量代谢的深刻变化有关。即使在缺血期间血浆中观察到的低葡萄糖水平下，葡萄糖转运活性也可能会进行适应性调整，以确保葡萄糖的输送，从而维持正常的细胞功能。在大脑中，主要的葡萄糖转运蛋白（GLUTs）在神经元中是GLUT3，在血脑屏障和神经胶质细胞的微血管内皮细胞中是GLUT1。脑缺血中参与GLUT调节的细胞内信号通路仍不清楚；然而，已经确定缺血会诱导它们表达的变化。在这篇综述中，我们描述了谷氨酸诱导的兴奋性毒性、线粒体损伤、葡萄糖剥夺和缺氧对大脑中GLUTs表达的影响。此外，我们讨论了GLUTs作为缺血治疗靶点的可能作用。尽管进行了大量研究，但目前中风的治疗选择非常有限，因此寻找新的选择尤为重要。很少有研究探讨上调GLUT在缺血性中风中的神经保护潜力；然而，有证据表明，增加GLUTs可能与一种保护机制有关。对GLUTs激活有益作用的更多了解为在新治疗策略开发中靶向GLUT提供了理论依据。
