Wang Chen X, Shuaib Ashfaq
Stroke Research Laboratory, University of Alberta, Edmonton, Alberta, Canada.
Drugs Aging. 2007;24(7):537-46. doi: 10.2165/00002512-200724070-00002.
Acute ischaemic stroke is a leading cause of death in the majority of industrialised countries and also in many developing countries. Free radicals are generated in the brain during ischaemic injury and these radicals are involved in the secondary injury processes. Several free radical scavengers have been developed and some of them have progressed into clinical trials. One of them, edaravone, has been approved by the regulatory authority in Japan for the treatment of stroke patients. Another scavenger, disodium 4-[(tert-butylimino)methyl] benzene-1,3-disulfonate N-oxide (NXY-059; disufenton), has demonstrated efficacy in a phase III clinical trial (SAINT [Stroke Acute Ischaemic NXY-059 Treatment study]-I) involving a large number of stroke patients. Unfortunately, SAINT II did not show efficacy in the treatment of stroke patients. The purpose of this article is to review the current development of antioxidant strategies, update recent findings for NXY-059 in the treatment of stroke patients, and discuss the future development of neuroprotective agents. Although the development of neuroprotective strategies for the treatment of stroke is challenging, progress in molecular and cellular neuroscience will uncover new information about stroke mechanisms, which should result in the realisation of neuroprotective therapy for this disease.
急性缺血性中风是大多数工业化国家以及许多发展中国家的主要死因。在缺血性损伤期间,大脑会产生自由基,这些自由基参与继发性损伤过程。已经开发了几种自由基清除剂,其中一些已进入临床试验阶段。其中一种依达拉奉已获日本监管机构批准用于治疗中风患者。另一种清除剂4-[(叔丁基亚氨基)甲基]苯-1,3-二磺酸钠N-氧化物(NXY-059;二磺富顿)在一项涉及大量中风患者的III期临床试验(SAINT[中风急性缺血性NXY-059治疗研究]-I)中显示出疗效。不幸的是,SAINT II在中风患者治疗中未显示出疗效。本文的目的是回顾抗氧化策略的当前进展,更新NXY-059在中风患者治疗方面的最新研究结果,并讨论神经保护剂的未来发展。尽管开发用于治疗中风的神经保护策略具有挑战性,但分子和细胞神经科学的进展将揭示有关中风机制的新信息,这应该会实现针对这种疾病的神经保护治疗。