Petty M A, Wettstein J G
CNS Pharmacology, Aventis Pharmaceuticals, Inc., Route 202-206, P.O. Box 6800, Bridgewater, NJ 08807, USA.
Brain Res Brain Res Rev. 2001 Aug;36(1):23-34. doi: 10.1016/s0165-0173(01)00062-5.
Although neuronal cells have long been thought to be the prime target of ischaemic insults, events which occur at the blood-vascular-parenchymal interface are necessary for the initiation of ischaemic tissue injury. This cascade of microvascular events includes fibrin accumulation, endothelium expression of leukocyte adhesion receptors, breakdown of the basal laminae with loss of astrocyte and endothelial cell contacts leading to blood-brain barrier disruption and consequently oedema formation and haemorrhagic transformation. Potential stroke treatments have been studied in the clinic and many have not been particularly successful, probably due to the delicate balance between improved outcome and adverse reactions as well as the window of opportunity for drug treatment after symptom onset. The only acute intervention trial demonstrating any benefit in patients was that of intravenous tissue plasminogen activator (tPA), administered within 3 h of the onset of symptoms of ischaemic stroke. Such treatment improved clinical outcome at 3 months, although there was an increased incidence of symptomatic haemorrhage [New Engl. J. Med. 333 (1995) 1581]. The recent progress made in defining the mechanisms involved in the initiation of ischaemic events, as described in this review, may lead to the identification of new strategies for intervention in the ischaemic cascade.
尽管长期以来人们一直认为神经元细胞是缺血性损伤的主要靶点，但缺血性组织损伤的起始需要在血管-实质界面发生一系列事件。这一系列微血管事件包括纤维蛋白积聚、白细胞黏附受体在内皮细胞上的表达、基膜破坏以及星形胶质细胞与内皮细胞接触丧失，进而导致血脑屏障破坏，最终形成水肿和出血性转化。临床上已经对潜在的中风治疗方法进行了研究，但许多方法并不特别成功，这可能是由于改善预后与不良反应之间的微妙平衡，以及症状出现后药物治疗的时机窗口。唯一一项显示对患者有任何益处的急性干预试验是静脉注射组织纤溶酶原激活剂（tPA），该药物在缺血性中风症状出现后3小时内给药。这种治疗方法改善了3个月时的临床预后，尽管有症状性出血的发生率有所增加[《新英格兰医学杂志》333（1995）1581]。如本综述所述，在确定缺血事件起始机制方面取得的最新进展可能会促使人们找到干预缺血级联反应的新策略。
