Martínez-Vila E, Sieira P I
Neurology Department, University Clinic, School of Medicine, Navarre University, Pamplona, Spain.
Cerebrovasc Dis. 2001;11 Suppl 1:60-70. doi: 10.1159/000049127.
In developed countries, ischemic stroke is one of the leading causes of death and neurological impairment. The two most important therapeutic approaches in patients with acute cerebral ischemia consist of improving cerebral blood flow and blocking the biochemical and metabolic changes at the ischemic cascade level. The significant advances made in the past decade in the knowledge of the physiopathological mechanisms of cerebral ischemia, and the development of new drugs have given rise to true expectations regarding treatment and the rejection of nihilist attitudes. In the past 15 years, based on the excellent results obtained in experimental models of ischemia, many clinical trials have been conducted with different neuroprotective drugs. The results obtained in most studies have been negative, or the studies were terminated early owing to side effects. However, some drugs (citicoline, clomethiazole, piracetam and ebselen) have shown a certain degree of clinical efficacy, limited to subgroups of patients, and with a narrow therapeutic window, longer-lasting in the case of citicoline. The design of new clinical trials with neuroprotective drugs requires adequate preclinical assessment and the use of the new magnetic resonance techniques for the selection of patients and the assessment of the efficacy of treatment. The new trends in neuroprotection in focal cerebral ischemia and the results of the clinical trials published to date are reviewed.
在发达国家,缺血性中风是导致死亡和神经功能障碍的主要原因之一。急性脑缺血患者最重要的两种治疗方法包括改善脑血流以及在缺血级联反应水平阻断生化和代谢变化。过去十年中,在脑缺血生理病理机制的认识方面取得的重大进展以及新药的研发,引发了人们对治疗的真切期望,并摒弃了虚无主义态度。在过去15年里,基于在缺血实验模型中获得的优异结果,针对不同神经保护药物开展了许多临床试验。大多数研究得到的结果均为阴性,或者研究因副作用而提前终止。然而,一些药物(胞磷胆碱、氯美噻唑、吡拉西坦和依布硒啉)已显示出一定程度的临床疗效,不过仅限于部分患者亚组,且治疗窗较窄,胞磷胆碱的疗效持续时间更长。设计新的神经保护药物临床试验需要进行充分的临床前评估,并运用新的磁共振技术来选择患者和评估治疗效果。本文综述了局灶性脑缺血神经保护的新趋势以及迄今已发表的临床试验结果。