Department of Neurology, University of Texas Medical School at Houston, Houston, TX 77030, USA.
Neurotherapeutics. 2011 Jul;8(3):434-51. doi: 10.1007/s13311-011-0040-6.
Stroke is one of the leading causes of death and disability worldwide. Current treatment strategies for ischemic stroke primarily focus on reducing the size of ischemic damage and rescuing dying cells early after occurrence. To date, intravenous recombinant tissue plasminogen activator is the only United States Food and Drug Administration approved therapy for acute ischemic stroke, but its use is limited by a narrow therapeutic window. The pathophysiology of stroke is complex and it involves excitotoxicity mechanisms, inflammatory pathways, oxidative damage, ionic imbalances, apoptosis, angiogenesis, neuroprotection, and neurorestoration. Regeneration of the brain after damage is still active days and even weeks after a stroke occurs, which might provide a second window for treatment. A huge number of neuroprotective agents have been designed to interrupt the ischemic cascade, but therapeutic trials of these agents have yet to show consistent benefit, despite successful preceding animal studies. Several agents of great promise are currently in the middle to late stages of the clinical trial setting and may emerge in routine practice in the near future. In this review, we highlight select pharmacologic and cell-based therapies that are currently in the clinical trial stage for stroke.
中风是全球范围内导致死亡和残疾的主要原因之一。目前，缺血性中风的治疗策略主要集中在减少缺血性损伤的范围，并在发生后尽早挽救濒死细胞。迄今为止，静脉注射重组组织型纤溶酶原激活物是美国食品和药物管理局唯一批准用于急性缺血性中风的治疗方法，但由于治疗窗口狭窄，其应用受到限制。中风的病理生理学非常复杂，涉及兴奋性毒性机制、炎症途径、氧化损伤、离子失衡、细胞凋亡、血管生成、神经保护和神经修复。在中风发生后的数天甚至数周内，受损大脑的再生仍然活跃，这可能为治疗提供第二个窗口。大量的神经保护剂被设计用来阻断缺血性级联反应，但这些药物的治疗试验尚未显示出一致的益处，尽管之前的动物研究取得了成功。目前有几种很有前途的药物处于临床试验的中晚期，可能在不久的将来会在常规实践中出现。在这篇综述中，我们重点介绍了目前处于临床试验阶段的中风的几种药物和细胞治疗方法。
