Jin Xinchun, Liu Jie, Liu Wenlan
The Central Laboratory of Shenzhen Second People's Hospital, Shenzhen University First Affiliated Hospital Shenzhen, China, 518035.
Curr Neurovasc Res. 2014;11(3):254-62. doi: 10.2174/1567202611666140530145643.
Tissue plasminogen activator (tPA) thrombolysis, remains to be the only United States Food and Drug Administration (FDA) approved treatment for acute ischemia stroke. However, the use of tPA has been profoundly constrained due to its narrow therapeutic time window and the increased risk of potentially deadly hemorrhagic complications. TPA-associated hemorrhagic transformation (HT) often occurs as a result of catastrophic failure of the blood brain barrier (BBB), wherein the affected cerebral capillaries can no longer hold blood constituents. Due to its direct contribution to edema and HT, reperfusion-associated BBB damage has been extensively studied, while BBB damage that occurs within the thrombolytic time window is largely neglected. Of note, ischemia-induced BBB damage in the early stroke stages is increasingly appreciated to negatively affect the safety and efficacy profiles of thrombolytic therapy for ischemic stroke. In this review, we discussed the recent findings of spatio-temporal evolution of BBB injury in the early stages of cerebral ischemia and its association with intracerebral hemorrhage following tPA thrombolysis. The increased understanding of early ischemic BBB damage and its close link to tPA-associated HT is of particular importance for developing new preventive and therapeutic strategies to reduce the hemorrhagic complications in stroke thrombolysis.
组织型纤溶酶原激活剂（tPA）溶栓仍然是美国食品药品监督管理局（FDA）批准的唯一用于急性缺血性中风的治疗方法。然而，由于其狭窄的治疗时间窗以及潜在致命性出血并发症风险的增加，tPA的使用受到了极大限制。tPA相关的出血性转化（HT）通常是血脑屏障（BBB）灾难性破坏的结果，其中受影响的脑毛细血管无法再容纳血液成分。由于其对水肿和HT的直接作用，再灌注相关的BBB损伤已得到广泛研究，而在溶栓时间窗内发生的BBB损伤在很大程度上被忽视。值得注意的是，越来越多的人认识到中风早期缺血诱导的BBB损伤会对缺血性中风溶栓治疗的安全性和有效性产生负面影响。在本综述中，我们讨论了脑缺血早期BBB损伤的时空演变及其与tPA溶栓后脑出血相关性的最新研究结果。对早期缺血性BBB损伤及其与tPA相关HT的密切联系的深入理解对于制定新的预防和治疗策略以减少中风溶栓中的出血并发症尤为重要。
