School of Medicine, Faculty of Medicine, University of Chile, Santiago, Chile.
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
CNS Neurol Disord Drug Targets. 2021;20(1):3-21. doi: 10.2174/1871527319666200910153431.
The underlying mechanism of cerebral injury occurring in patients with acute ischemic stroke involves a key pathophysiological role of oxidative stress. Thus, reactive oxygen species are related to the development of brain edema, calcium overload, mitochondrial dysfunction, excitotoxicity, iron release and inflammation. Nevertheless, although experimental studies have tested the use of antioxidants as an adjuvant therapy in this setting, clinical data and randomized trials are still lacking. Current approved pharmacological therapy is aimed at reperfusion strategies; however, the therapeutic window is limited and also challenged by the injury known to result from the reperfusion. We have recently defined a time-course occurrence of pathological events triggered by reperfusion-dependent increased reactive oxygen species, thus suggesting the beneficial role of the pertinent use of antioxidants. The present study was aimed to support the hypothesis that an enhanced antioxidant neuroprotection could be achieved by the use of two or more antioxidants opportunely provided to ischemic stroke patients focused against the specific mechanism occurring throughout the pathophysiological process. From this paradigm, using an underexplored therapeutic principle, it could be suggested that antioxidant-based therapy is a novel, promising, safe, available and cost-effective strategy against the deleterious effects of ischemic stroke that needs to be further studied in clinical protocols.
急性缺血性脑卒中患者发生脑损伤的潜在机制涉及氧化应激的关键病理生理作用。因此,活性氧与脑水肿、钙超载、线粒体功能障碍、兴奋毒性、铁释放和炎症的发展有关。然而,尽管实验研究已经测试了将抗氧化剂作为辅助治疗剂用于这种情况,但仍缺乏临床数据和随机试验。目前批准的药物治疗旨在进行再灌注策略;然而,治疗窗口有限,而且再灌注引起的损伤也带来了挑战。我们最近定义了由再灌注依赖性增加的活性氧触发的病理事件的时程发生,从而表明适当使用抗氧化剂具有有益作用。本研究旨在支持以下假设,即通过对缺血性脑卒中患者适时使用两种或更多种抗氧化剂来增强抗氧化神经保护作用,可以针对整个病理生理过程中发生的特定机制来实现。从这个范例中,可以看出,基于抗氧化剂的治疗是一种新颖、有前途、安全、可用且具有成本效益的策略,可以对抗缺血性脑卒中的有害影响,需要在临床方案中进一步研究。